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anastomosis Absorbable Polyglyconate (Maxon) Braided/Absorbable 28 d 6 mo GI, muscle, fascia Panacryl Braided/Absorbable >6 mo >24 mo Fascia, tendons (continued ) 17 347 TABLE 17–1 (Continued) NONABSORBABLE Suture (Brand Name) Description Common Uses Nylon (Dermalon, Monofilament Skin, drains Ethilon Nylon (Nurolon) Braided Tendon repair Polyester (Ethibond, Braided Cardiac, tendon Tycron) Polypropylene Monofilament Vessel, fascia, skin (Prolene) Silk GI, vessel ligation, drains Stainless steel Monofilament Fascia, sternum *When suture looses approximately 50% strength. †Approximate. 348 Clinician’s Pocket Reference, 9th Edition • Face: 5-0 and 6-0 nylon or polypropylene where cosmetic concerns are important • Scalp: 3-0 nylon or polypropylene • Trunk or extremities: 4-0 or 5-0 nylon or polypropylene Use 3-0 and 4-0 absorbable sutures such as Dexon or Vicryl to approximate deep tissues. Skin is usually best closed by using interrupted sutures placed with good approximation with a minimum amount of tension or by a running subcuticular suture. Tissue adhesives may be used selectively (see page 358). Suture patterns are discussed in the next section. Suture marks (“tracks”) are the result of excessive tension on the tissue or leaving the su- tures in for too long. Thus, the length of time and the technique used are probably more im- portant in determining the final result than is the suture used in most cases. 1. Remove all foreign materials and devitalized tissues by sharp excision (debridement). Clean the wound with plain saline (antiseptic solutions used on wound cleansing should be discouraged because they can be toxic to viable cells). A useful technique in- volves irrigation with at least 200 mL of saline through a 35-mL syringe and a 19- gauge needle. Anesthesia may be necessary before any of this is done. If all the debris is not removed, traumatic “tattooing” of the skin may result. 2. In general, do not suture infected or contaminated wounds, lacerations more than 6–12 h old (24 h on the face), missile wounds, and human or animal bites without surgical consultation. 3. Anesthetize the wound by infiltrating it with an agent such as 0.5% or 1% lidocaine (Xylocaine). The maximum safe dosage is 4.5 mg/kg (about 28 mL of a 1% solution in an adult). Lidocaine and the other local anesthetic agents are available with epinephrine (1:100,000 or 1:200,000) added to produce local vasoconstriction that prolongs the anesthetic effect and helps decrease systemic side effects and bleeding. Epinephrine should be used with caution, particularly in patients with a history of hypertension, and should not be used on the digits, toes, or penis. 1 mL of 1:10 NaHCO3 can be mixed with 9 mL of lidocaine to help minimize the discomfort of the injection. Commonly used local anesthetics are compared in Table 17–2. 4. When using local anesthetics, always aspirate before injecting to prevent intravascular injection of the drug. Anesthetize with a 26–30-gauge needle. Symptoms of toxicity from local anesthetics includes twitching, restlessness, drowsiness, light-headedness, and seizures. 5. Close the wound using one of the suturing patterns discussed in the next section. Use fine-toothed forceps (Adson or Brown-Adson) with gentle pressure to handle skin edges to decrease trauma. The toothed forceps are less traumatic to the skin than other forceps with flat surfaces that may crush the tissue. 17 6. Cover the wound and keep it dry for at least 24–48 h. Dry gauze or Steri-Strips are suf- ficient. On the face, simply covering with antibiotic ointment is often used, especially around the eyes or mouth. After that, the patient may shower and wet the wound. This will not increase the risk of infection. 7. Finally, keep tetanus and antibacterial prophylaxis in mind, particularly for contami- nated wounds (Table 17–3, page 350). SUTURING PATTERNS Opinions vary greatly on the ideal technique for skin closure. The following are the com- mon techniques used for approximation of skin. Critical to any suturing technique is making certain that the edges of the wound closely approximate without overlapping or inversion and that there is no tension. Remember “approximation without strangulation” or eversion 17 349 TABLE 17–2 Local Anesthetic Comparison Chart for Commonly Used Injectable Agents Maximum Dose Proprietary Volume in Agent Names Onset Duration mg/kg 70-kg Adult* Bupivacaine Marcaine, 7–30 min 5–7 h 3 70 mL of Sensoricaine 0.25% solution Lidocaine Xylocaine, 5–30 min 2 h 4 28 mL of 1% Anestacon solution Lidocaine with 5–30 min 2–3 h 7 50 mL of 1% epinephrine solution (1:200,000) Mepivacaine Carbocaine 5–30 min 2–3 h 7 50 mL of 1% solution Procaine Novocaine Rapid 30 min–1 h 10–15 70–105 mL of 1% solution *To calculate the maximum dose if the patient is not a 70-kg adult, use the fact that a 1% solution has 10 mg of drug per milliliter. 350 Clinician’s Pocket Reference, 9th Edition TABLE 17–3 Tetanus Prophylaxis Clean, Minor All Other History of Absorbed Wounds Wounds* Tetanus Toxoid Immunization Td† TIG‡ Td† TIG‡ Unknown or <3 doses Yes No Yes Yes <3 doses§ No** No No†† No *Such as, but not limited to, wounds contaminated with dirt, feces, soil, saliva, etc; punc- ture wounds; avulsions; and wounds resulting from missiles, crushing, burns, and frostbite. †Td = tetanus-diphtheria toxoid (adult type), 0.5 mL IM. • For children <7 y of age, DPT (DT, if pertussis vaccine is contraindicated) is preferred to tetanus toxoid alone. • For persons >7 years of age, Td is preferred to tetanus toxoid alone. • DT = diphtheria-tetanus toxoid (pediatric), used for those who cannot receive pertussis. ‡TIG = tetanus immune globulin, 250 U IM. §If only three doses of fluid toxoid have been received, then a fourth dose of toxoid, preferably an absorbed toxoid, should be given. **Yes, if >10 y since last dose. ††Yes, if >5 y since last dose. Source: Based on guidelines from the Centers for Disease Control and reported in MMWR. of the skin edges gives the best results (Figure 17–1). Figures 17–2 through 17–6 illustrate the commonly used suturing patterns. These include the simple interrupted suture (Fig. 17–2), running (locked or unlocked) suture (Fig. 17–3), vertical mattress suture (Fig. 17–4), horizontal mattress suture (Fig. 17–5), and subcuticular suture (Fig. 17–6). SURGICAL KNOTS There are two basic knot-tying techniques: the handed tie and the instrument tie. The two- handed tie is easier to learn than the one-handed tie, although one-handed ties may be more useful in certain situations (eg, with deep cavities or where speed is essential). Some pro- 17 grams frown on one-handed tying, especially for physicians early in their careers. Instru- ment ties are more useful for closing skin and for emergency room laceration repair. Figures 17–7, page 355, and 17–8, page 356, show the technique for tying a two-handed square knot. This is the standard surgical knot that should be learned first. Figure 17–9, page 357, shows the technique for an instrument tie. SUTURE REMOVAL The longer that suture material is left in place, the more scarring it will produce. Using a topical antibiotic (Polysporin, others) ointment on the wound is helpful in decreasing suture tract epithelialization. This epithelialization results from crusting around the suture that in- creases suture marks and subsequent scarring. Sutures can be safely removed when a wound has developed sufficient tensile strength. Situations vary greatly, but general guidelines for 17 Suturing Techniques and Wound Care 351 Correct method Unequal distance Skin inversion Skin overlap Excessive tension FIGURE 17–1 Proper method for simple interrupted suturing of a skin wound com- pared with incorrect techniques that result in poor scars from skin overlap, skin inver- sion, or necrosis of the skin edges because of excessive tension. (Reprinted, with permission from: Stillman RM [ed]: Surgery: Diagnosis and Therapy, Appleton & Lange, Stamford CT, 1989.) 17 FIGURE 17–2 Simple interrupted suture. “Bites” are taken through the thickness of the skin, and the width of each stitch should equal the distance between sutures to avoid inverting the skin edges. 352 Clinician’s Pocket Reference, 9th Edition FIGURE 17–3 Continuous running suture. It allows rapid closure, but depends on only two knots for security and may not allow precise approximation of the skin edges. “Locking” each stitch, as shown, may increase scarring. 17 FIGURE 17–4 Vertical interrupted mattress suture. It allows precise approximation of the skin edges with little tension, but may result in more scarring than a simple stitch. The needle is placed in the skin in a “far, far, near, near” sequence. 17 Suturing Techniques and Wound Care 353 FIGURE 17–5 Horizontal interrupted mattress suture. This is an everting stitch that is more frequently used in fascia than in skin. It is often used in calloused skin such as the palms and soles. removing sutures from different areas of the body are: face and neck, 3–5 d; scalp and body, 5–7 d; and extremities, 7–12 d. Any suture material or skin clips can be removed earlier if they have been reinforced with a deep absorbable suture or with the application of Steri- Strips after the suture is removed. Steri-Strips will stay in place more securely if tincture of benzoin (spray or solution) is applied to the skin and allowed to dry before the Steri-Strips are applied. The length of time absorbable sutures remain in tissues is shown in Table 17–1. Suture Removal Procedure 17 1. Gently clear away any dried blood with saline and gauze. Verify that the wound is suffi- ciently healed to allow suture removal. Use a forceps to gently elevate the knot off the skin. This can be uncomfortable for the patient. 2. Cut the suture as close to the skin as possible so that a minimal amount of “dirty su- ture” is dragged through the wound. When removing continuous sutures, cut and pull out each section individually. Never pull a knot through the skin. 3. The use of skin staples is commonplace in the operating room because of the rapidity of closure and the nonreactive nature of the steel staples. These are typically removed 3–5 d after surgery (abdominal incisions) as shown in Figure 17–10. Because these are removed fairly quickly, reinforce the incision with Steri-Strips. When removing skin staples, make sure that the staple is completely reformed (see Figure 17–10) before re- moval to decrease patient discomfort. 354 Clinician’s Pocket Reference, 9th Edition 1 2 3 4 17 5 6 7 8 FIGURE 17–6 Subcuticular closure is usually performed with continuous, horizon- tally applied intradermal sutures. These are ideal for linear cosmetic closures be- cause they eliminate possible cross-hatching deformities. If nonabsorbable suture material (eg, 5-0 or 6-0 Prolene) is used, the knot is placed on the skin and pulled taut. If absorbable (5-0 or 6-0 Dexon or Vicryl) is used, the knot is usually buried as shown. (Reprinted, with permission from: Stillman RM [ed]: Surgery: Diagnosis and Therapy, Appleton & Lange, Stamford CT, 1989.) 17 Suturing Techniques and Wound Care 355 A B C D 17 E FIGURE 17–7 Technique for tying the two-handed square knot. Suture ends are uncrossed as step A begins (continued in Figure 17–8). 356 Clinician’s Pocket Reference, 9th Edition F G H I 17 J FIGURE 17–8 The two-handed square knot (continued from Figure 17–7). Hands must be crossed at the end of the first loop tie (step F) to give a flat knot; hands are not crossed at the end of the second loop tie (step J). 17 Suturing Techniques and Wound Care 357 A B C D E F 17 G FIGURE 17–9 The instrument tie. Begin with either a single or double (illustrated) looping of the lower end of the suture around the needle holder. The first loop is laid flat without crossing the hands. Hands must be crossed after the second loop tie (step G) to produce a flat square knot. 358 Clinician’s Pocket Reference, 9th Edition Staple in place Removed staple FIGURE 17–10 Removal of skin staples. The staple removal instrument is passed beneath the staple and completely closed. Be sure that the staple is completely “re- formed” before removal to decrease patient discomfort. (Courtesy of Ethicon, Inc.) TISSUE ADHESIVES Octyl cyanoacrylate (Dermabond) is a topical skin adhesive (very similar to cyanoacrylate glue) that holds wound edges together. It is useful in wounds that are clean and easily op- posed and for young children, for whom suture removal may be a problem. The wound should be nonmucosal on the face, torso, or extremity. It is recommended for wounds <8 cm with

minimal tension (skin gap should be <0.5 cm). It is also useful for stabilizing wounds if the sutures were removed very early in order to minimize suture marks. It should not be used for puncture wounds, bites or wounds that need debridement, or in regions subjected to frequent movement (ie, hand or finger). 17 Gently approximate the wound edges with fingers or a forceps and place a small coating of the glue directly on the wound. After 2–3 min (after the glue has dried), an additional one or two coats may be applied. The glue will spontaneously separate in approximately 5–10 d. Once the glue is in place and stable, it is not necessary to use any topical medication or oint- ment. The patient may shower for brief periods. If the adhesive is too tacky, too much glue has been applied. 18 RESPIRATORY CARE Respiratory Therapy Bronchopulmonary Hygiene Pulmonary Function Tests Topical Medications Differential Diagnosis of PFTs Metered-Dose Inhalers Oxygen and Humidity Supplements RESPIRATORY THERAPY Respiratory therapy is a vital component of health care. The objective is the treatment and care of all types of patients with cardiopulmonary diseases. Functions of the respiratory therapist include emergency care, ventilatory support, airway management, oxygen therapy, humidity and aerosol therapies, chest physiotherapy, physiologic monitoring, and pul- monary diagnostics. PULMONARY FUNCTION TESTS PFTs are useful in diagnosing a variety of pulmonary disorders. Common PFTs include spirometry, lung volume determinations, and diffusing capacity. Important measures include the FVC and the FEV1. Spirometry may identify obstructive airway diseases such as asthma or emphysema when the ratio of FEV1/FVC is less than 70%, or restrictive lung diseases such as sarcoidosis or ankylosing spondylitis when both the FVC and FEV1 are reduced. Spirometry may also be an important part of a preoperative evaluation. Spirograms can be obtained before and after the administration of bronchodilators if they are not contraindi- cated (ie, history of intolerance). Bronchodilator responsiveness will help in predicting the response to treatment and in identifying asthma. Lung volumes commonly determined by helium dilution must be ordered to definitively diagnose restrictive lung disease. This is usually indicated by TLC less than 80% of pre- dicted normal. Diffusion capacity is important in the diagnosis of interstitial lung disease or pulmonary vascular disease, where it is reduced. It is also frequently followed to determine the response to therapy in interstitial diseases. Obstructive pulmonary diseases include asthma, chronic bronchitis, emphysema, 18 bronchiectasis, and lower airway obstruction. Restrictive pulmonary disease includes inter- stitial pulmonary diseases, diseases of the chest wall, and neuromuscular disorders. Intersti- tial disease may be due to inflammatory conditions [usual interstitial pneumonitis (UIP)], inhalation of organic dusts (hypersensitivity pneumonitis), inhalation of inorganic dusts (as- bestosis), or systemic disorders with lung involvement (sarcoidosis). Normal PFT values vary with age, sex, race, and body size. Normal values for a given patient are established from studies of normal populations and are provided along with the results. Arterial blood gases should be included in all PFTs. Typical volumes and capacities are illustrated in Figure 18–1. 359 Copyright 2002 The McGraw-Hill Companies, Inc. Click Here for Terms of Use 360 Clinician’s Pocket Reference, 9th Edition IRV IC FVC TV ERV FRC RV RV FVC = Forced vital capacity ERV = expiratory reserve volume RV = residual volume IRV = inspiratory reserve volume FRC = functional residual capacity IC = inspiratory capacity TV = tidal volume FIGURE 18–1 Lung volumes in the interpretation of pulmonary function tests. Tidal Volume (TV): Volume of air moved during a normal breath on quiet respiration 18 Forced Vital Capacity (FVC): Maximum volume of air that can be forcibly expired after full inspiration Functional Residual Capacity (FRC): Volume of air in the lungs after a normal tidal expiration (FRC = reserve volume + expiratory reserve volume) Total Lung Capacity (TLC): Volume of air in the lungs after maximal inspiration Forced Expired Volume in 1 Second (FEV1): Measured after maximum inspira- tion, the volume of air that can be expelled in 1 s 18 Respiratory Care 361 Vital Capacity (VC): Maximum volume of air that can be exhaled from the lungs after a maximal inspiration Residual Volume (RV): The volume of air remaining in the lungs at the end of a maxi- mal exhalation DIFFERENTIAL DIAGNOSIS OF PFTS Table 18–1 shows the differential diagnosis of various PFT patterns. When interpreting PFTs, remember that some patients may have combined restrictive and obstructive diseases such as emphysema and asbestosis. OXYGEN AND HUMIDITY SUPPLEMENTS Table 18–2 describes various methods of oxygen and humidity supplementation. TABLE 18–1 Differential Diagnosis of Pulmonary Function Tests Restrictive Obstructive Test Disease Disease FVC ↓ N or ↓ TLC ↓ ↑ FEV1/FVC N or ↑ ↓ FEV1 ↓ ↓ OBSTRUCTIVE AIRWAYS DISEASE (COPD) Test Normal Mild Moderate Severe FEV1 (% of VC) >75 60–75 40–60 <40 RV (% of predicted) 80–120 120–150 150–175 >200 RESTRICTIVE LUNG DISEASE Test Normal Mild–Moderate Severe 18 FVC (% of predicted) >80 60–80 50–60 <50 FEV1 (% of VC) >75 >75 >75 >75 RV (% of predicted) 80–120 80–120 70–80 70 Abbreviations: N = normal; ↑ = increased, ↓ = decreased; FVC = forced vital capacity; TLC = total lung capacity; RV/FRC = residual volume/functional residual capacity; FEV1 = forced expiratory volume in 1s; VC = vital capacity. 362 Clinician’s Pocket Reference, 9th Edition TABLE 18–2 Various Methods of Oxygen and Humidity Supplementation 02 Device Range L/min Fi02 Uses Nasal cannula Low 1–6 0.24–0.5 COPD, general oxygen needs Simple face mask Medium 6–8 0.5–0.6 General oxygen needs Partial rebreathing High 8–12 0.6–0.7 High oxygen face mask emergency needs Nonrebreathing High 8–12 0.7–0.95 High oxygen face mask emergency needs Venturi mask Low–medium — 0.24–0.50 COPD (can specify exact Fi02) Note: Fi02 may vary with fluctuations in the patient’s minute ventilation when using a nasal cannula. This is not true when using the Venturi mask because it is a “high-flow oxygen en- richment system” that supplies three times the patient’s minute ventilation, thus providing an exact Fi02. Abbreviation: COPD = chronic obstructive pulmonary disease. Humidity Therapy Humidity generators are divided into humidifiers and nebulizers. Patients with intact upper airways do not need as high a percentage of relative humidity (% RH) as do patients with ar- tificial airways (endotracheal tubes or tracheostomy tubes). Artificial airways require higher humidity to prevent secretions from obstructing the tubes. To bring the % RH of the inspired gas up to room humidity (30–40% RH) when using the nasal cannula, simple oxygen mask, partial rebreathing mask, or nonrebreathing mask, the bubble-diffuser humidifier is the de- vice of choice. To provide medium to high levels of % RH, aerosol devices such as the face tent, aerosol mask, aerosol T piece, and aerosol collar are the devices of choice. The humidity 18 generator for these devices is the aerosol-jet nebulizer, which can provide cool or heated mist. The gas that powers the nebulizer may be blended to any desired inspired oxygen con- centration (FiO2). BRONCHOPULMONARY HYGIENE The following is a listing of the modalities available through the respiratory care or nursing services of most hospitals. All are designed to help patients with their bronchopulmonary hygiene, more commonly referred to as “pulmonary toilet.” Bronchopulmonary hygiene is defined as maintenance of clear airways and removal of secretions from the tracheo- 18 Respiratory Care 363 bronchial tree. This is important for routine postoperative surgical patients, medical patients with obstructive pulmonary diseases, or any patient with excessive respiratory secretions. Aerosol (Nebulizer) Therapy Aerosolized medications such as bronchodilators and mucolytic agents can be delivered via nebulizer for spontaneously breathing, awake patients or intubated patients. Indications • Treatment of COPD, acute asthma, cystic fibrosis, and bronchiectasis • Help in inducing sputum for diagnostic tests Goals • Relief of bronchospasm • Help in decreasing the viscosity and in clearing of secretions To Order: Specify the following: • Frequency • Heated or cool mist • Medications: In sterile water or NS • FiO2 • Example. Albuterol 2.5 mg in 3 mL of sterile saline, FiO2 0.28. Chest Physiotherapy This technique uses P&PD along with coughing and deep breathing exercises (TC&DB). P&PD is performed by positioning the patient so that the involved lobes of the lung are placed in a dependent drainage position and then using a cupped hand or vibrator to percuss the chest wall. Nasotracheal suctioning is quite uncomfortable for the patient but is still use- ful in the appropriate clinical setting in the absence of significant coagulopathy. Indication • Treatment of pneumonia, atelectasis, and diseases resulting in weak or ineffective coughing To Order 1. P&PD: Specify the following: • Frequency • Segments or lobes involved (RUL, etc) • Duration • Drainage only 2. TC&DB: Ordered on a timed schedule or as needed 18 • Example. P&PD qid of RUL and RML 5 min/lobe or TC&DB q4h. Incentive Spirometry This method encourages patients to make a maximal and sustained inspiratory effort to help reinflate the lungs or prevent atelectasis. Indications • Treatment of patients at risk for developing postoperative pulmonary complications • Treatment and prevention of atelectasis, especially in postoperative setting 364 Clinician’s Pocket Reference, 9th Edition Goals Set for the patient depending on the device available: • Lighting lights • Moving Ping-Pong balls • Moving colored fluids in “blow bottles” To Order Specify the following: • Frequency (such as 10 min q1–2h while awake) • Device (if you have a preference) Example. Incentive spirometry 10 min every hour with blow bottle. TOPICAL MEDICATIONS The following agents can be added to aerosol therapy to prevent or treat pulmonary compli- cations caused by bronchoconstriction, mucosal congestion, or inspissated secretions. Re- member, even though these are primarily topical agents, some systemic absorption can often occur. Acetylcysteine (Mucomyst): A mucolytic agent useful for treating retained mucoid secretions; inspissated secretions; and impacted mucoid plugs seen in diseases such as COPD, cystic fibrosis, and pneumonia. A bronchodilator should be given along with Mu- comyst. Usual Adult Dosage. 1–3 mL of 20% acetylcysteine in 0.5 mL (2–10 mg) of Bronkosol Albuterol (Ventolin, Proventil): A short-acting selective bronchodilator with princi- pally beta-2 activity; can cause tachycardia. Onset 15 min. Peak effect at 0.5–1 h, duration 3–5 h Usual Dosage. 2.5 mg in 3 mL NS q4h Metaproterenol (Alupent, Metaprel): A short-acting bronchodilator with both beta- 1 and beta-2 activity; can cause tachycardia. Peak effect at 0.5–1 h, duration 3–5 h. Usual Dosage. 0.3 mL (10–15 mg) of a 5% solution in 2.5 mL NS bid–qid Racemic Epinephrine: Contains both d and l forms of epinephrine. Useful because the alpha effects result in mucosal vasoconstriction that reduces mucosal engorgement and the bronchodilation lessens the risk of hypoxemia. Most useful for laryngotracheobronchitis and immediately after extubation in children. Usual Dosage. 0.125–0.5 mL (3–10 mg) in 2.5 mL NS 18 Ipratropium Bromide (Atrovent): A parasympatholytic bronchodilating agent that causes bronchodilation and a decrease in secretions with “drying” of the respiratory mu- cosa. This is minimally absorbed and rarely results in tachycardia. Onset 45 min, duration 4–6 h Usual Dosage. 0.5 mg in 3 mL NS qid Atropine: A parasympatholytic agent that causes bronchodilation and a decrease in se- cretions with “drying” of the respiratory mucosa. This is readily absorbed and, therefore has cardiac effects (tachycardia). Usual Dosage. 0.025–0.05 mg/kg of a 1% solution 18 Respiratory Care 365 METERED-DOSE INHALERS All bronchodilating agents can be effectively delivered by metered-dose inhaler as long as proper technique is used. For these devices to be successful, in-patients must be well trained or have the assistance of a nurse or respiratory therapist. Albuterol and ipratropium bromide (Atrovent) can each be delivered two puffs q4h. A combination bronchodilator (Combivent) containing the equivalent of one puff of each is also available and provides synergistic bron- chodilatation. 18 This page intentionally left blank. 19 BASIC ECG READING Introduction Cardiac Hypertrophy Basic Information Myocardial Infarction Axis Deviation Electrolyte and Drug Effects Heart Rate Miscellaneous ECG Changes Rhythm INTRODUCTION The formal procedure for obtaining a readable ECG is given in Chapter 13, page 266. Every electrocardiogram should be approached in a systematic, stepwise fashion. Many automated ECG machines can give a preliminary interpretation of a tracing; however, all automated in- terpretations require analysis and sign-off by a physician. Determine each of the following: • Standardization. With the ECG machine set on 1 mV, a 10-mm standardization mark (0.1 mV/mm) is evident (Figure 19–1). • Axis. If the QRS

is upright (more positive than negative) in leads I and aVF, the axis is normal. The normal axis range is –30 degrees to +105 degrees. • Intervals. Determine the PR, QRS, and QT intervals (Figure 19–2). Intervals are measured in the limb leads. The PR should be 0.12–0.20 s, and the QRS, <0.12 s. The QT interval increases with decreasing heart rate, usually <0.44 s. The QT inter- val usually does not exceed one half of the RR interval (the distance between two R waves). • Rate. Count the number of QRS cycles in a 6-s strip and multiply it by 10 to roughly estimate the rate. If the rhythm is regular you can be more exact in determining the rate by dividing 300 by the number of 0.20-s intervals (usually depicted by darker shading) and then extrapolating for any fraction of a 0.20-s segment. • Rhythm. Determine whether each QRS is preceded by a P wave, look for variation in the PR interval and RR interval (the duration between two QRS cycles), and look for ectopic beats. • Hypertrophy. One way to determine LVH is to calculate the sum of the S wave in 19 V1 or V2 plus the R wave in V5 or V6. A sum >35 indicates LVH. Some other criteria for LVH are R >11 mm in aVL or R in I + S in aVF >25 mm. • Infarction or Ischemia. Check for the presence of ST-segment elevation or depres- sion, Q waves, inverted T waves, and poor R-wave progression in the precordial leads. A more detailed discussion of each of these categories is presented in the following sections. 367 Copyright 2002 The McGraw-Hill Companies, Inc. Click Here for Terms of Use 368 Clinician’s Pocket Reference, 9th Edition 0.04 s 0.20 s FIGURE 19–1 Examples of a 10-mm standardization mark and time marks and standard electrocardiogram paper running at 25 mm/s. BASIC INFORMATION Equipment Bipolar Leads • Lead I: Left arm to right arm • Lead II: Left leg to right arm • Lead III: Left leg to left arm Precordial Leads: V1 to V6 across the chest, as shown in the section on electrocardio- grams in Chapter 13 (see Figure 13–9, page 267). ECG Paper: With the ECG machine set at 25 mm/s, each small box represents 0.04 s and each large box 0.2 s (see Figure 19–1, above). Most ECG machines automatically print a standardization mark. 19 Normal ECG Complex Note: A small amplitude in the Q, R, or S wave is represented by a lowercase letter; a large amplitude by an uppercase letter. The pattern shown in Figure 19–2 could also be noted as qRs. • P Wave. Caused by depolarization of the atria. With normal sinus rhythm, the P wave is upright in leads I, II, aVF, V4, V5, and V6 and inverted in aVR. 1 mV 10 mm 1 mm 19 Basic ECG Reading 369 R VAT ST segment PR segment T P P U J PR interval Q S Isoelectric line QRS interval QT interval QU interval 0 0.2 0.4 0.6 0.8 0.04 s Time (s) FIGURE 19–2 Diagram of the electrocardiographic complexes, intervals, and seg- ments. The U wave is normally not well seen. (Reprinted, with permission, from: Goldman MJ [ed]: Principles of Clinical Electrocardiography, 12th ed. Lange Med- ical Publications, Los Altos CA, 1986.) • QRS Complex. Represents ventricular depolarization • Q Wave. The first negative deflection of the QRS complex (not always present and, if present, may be pathologic) • R Wave. The first positive deflection (R) is the positive deflection that sometimes occurs after the S wave) • S Wave. The negative deflection following the R wave • T Wave. Caused by repolarization of the ventricles and follows the QRS complex. Normally upright in leads I, II, V3, V4, V5, and V6 and inverted in aVR 19 AXIS DEVIATION The term axis, which represents the sum of the vectors of the electrical depolarization of the ventricles, gives some idea of the electrical orientation of the heart in the body. In a healthy person, the axis is downward and to the left, as shown in Figure 19–3. Voltage (mV) 1 mm 10 mm = 1 mV 370 Clinician’s Pocket Reference, 9th Edition I I AVF –90∞ AVF LAD AVL Extreme RAD 180∞ 0∞ I I I Normal +120∞ +60∞ AVF III +90∞ II AVF AVF FIGURE 19–3 Graphic representation of the “axis deviation.” Electrocardio- graphic representations of each type of axis are shown in each quadrant. The large arrow is the normal axis. The QRS axis is midway between two leads that have QRS complexes of equal ampli- tude, or the axis is 90 degrees to the lead in which the QRS is isoelectric, that is, the ampli- tude of the R wave equals the amplitude of the S wave. • Normal Axis. QRS positive in I and aVF (0–90 degrees). Normal axis is actually –30 to 105 degrees • LAD. QRS positive in I and negative in aVF, –30 to –90 degrees • RAD. QRS negative in I and positive in aVF, +105 to +180 degrees • Extreme Right Axis Deviation. QRS negative in I and negative in aVF, +180 to 19 +270 or –90 to –180 degrees Clinical Correlations • RAD. Seen with RVH, RBBB, COPD, and acute PE (a sudden change in axis toward the right), as well as in healthy individuals (occasionally) • LAD. Seen with LVH, LAHB (–45 to –90 degrees), LBBB, and in some healthy in- dividuals 19 Basic ECG Reading 371 HEART RATE Bradycardia: Heart rate <60 bpm Tachycardia: Heart rate >100 bpm Rate Determination: Figure 19–4. • Method 1. Note the 3-s marks along the top or bottom of the ECG paper (15 large squares). The approximate rate equals the number of cycles (ie, QRSs) in a 6-s strip × 10. • Method 2. (for regular rhythms). Count the number of large squares (0.2-s boxes) between two successive cycles. The rate is equal to 300 divided by the number of squares. Extrapolate if the QRS complex does not fall exactly on the 0.2-s marks (eg, if each QRS complex is separated by 2.4 0.20-s segments, the rate is 120 bpm. The rate between two 0.20-s segments is 150 bpm, and between three 0.20-s segments is 100 bpm. RHYTHM Sinus Rhythms Normal: Each QRS preceded by a P wave (which is positive in II and negative in aVR) with a regular PR and RR interval and a rate between 60 and 100 bpm (Figure 19–5) Sinus Tachycardia: Normal sinus rhythm with a heart rate >100 bpm and <180 bpm (Figure 19–6) Clinical Correlations. Anxiety, exertion, pain, fever, hypoxia, hypotension, increased sympathetic tone (secondary to drugs with adrenergic effects [eg, epinephrine]), anticholin- ergic effect (eg, atropine), PE, COPD, AMI, CHF, hyperthyroidism, and others Sinus Bradycardia: Normal sinus rhythm with a heart rate <60 bpm (Figure 19–7) Clinical Correlations. Well-trained athlete, normal variant, secondary to medications (eg, beta-blockers, digitalis, clonidine), hypothyroidism, hypothermia, sick sinus syndrome (tachy–brady syndrome), and others 19 FIGURE 19–4 Sample strip for rapid rate determination (see text for procedure). Estimating the rate by counting the number of beats (eight) in the two 3-s intervals. The rate is 8 × 10, or 80 bpm (method 1). Using method 2, each beat is separated from another beat by four 0.20-s intervals, so you divide 300 by 4, and the rate is 75 bpm. Because the beats are separated by exactly four beats, you do not need to extrapolate. 372 Clinician’s Pocket Reference, 9th Edition FIGURE 19–5 Normal sinus rhythm. Treatment • If asymptomatic (good urine output, adequate BP, and normal sensorium), no ther- apy needed. • If hypotensive or disoriented: See Chapter 21, page 460 Sinus Arrhythmia: Normal sinus rhythm with a somewhat irregular heart rate. Inspira- tion causes a slight increase in rate; expiration decreases the rate. Normal variation between inspiration and expiration is 10% or less. Atrial Arrhythmias PAC: Ectopic atrial focus firing prematurely followed by a normal QRS (Figure 19–8). The compensatory pause following the PAC is partial; the RR interval between beats 4 and 6 is less than between beats 1 and 3 or 6 and 8. Clinical Correlations. Usually not of clinical significance; can be caused by stress, caf- feine, and myocardial disease PAT: A run of three or more consecutive PACs. The heart rate is usually between 140 and 250 bpm. The P wave may not be visible, but the RR interval is very regular (Figure 19–9). Clinical Correlations. Can be seen in healthy individuals but also occurs with a variety of heart diseases. Symptoms include palpitations, light-headedness, and syncope. Treatment • Increase Vagal Tone. Valsalva maneuver or carotid massage 19 FIGURE 19–6 Sinus tachycardia. The rate is 120–130 bpm. 19 Basic ECG Reading 373 FIGURE 19–7 Sinus bradycardia. The rate is approximately 38 bpm. • Medical Treatment. Can include adenosine, verapamil, digoxin, edrophonium, or beta-blockers (propranolol, metoprolol, and esmolol). Verapamil and beta-blockers should be used cautiously at the same time because asystole can occur. • Cardioversion with Synchronized DC Shock. Particularly in the hemodynamically unstable patient (see Chapter 21, page 467) MAT: An atrial arrhythmia that originates from ectopic atrial foci. It is characterized by varying P-wave morphology and PR interval and is irregular (Figure 19–10). Clinical Correlations. Most commonly associated with COPD, also seen in elderly pa- tients, CHF, diabetes, or use of theophylline. Antiarrhythmics are often ineffective. Treat the underlying disease. AFib: Irregularly irregular rhythm with no discernible P waves. The ventricular rate usu- ally varies between 100 and 180 bpm (Figure 19–11). The ventricular response is slower with digoxin, verapamil, or beta-blocker therapy and with AV nodal disease. Clinical Correlations. Seen in some healthy individuals but commonly associated with organic heart disease (CAD, hypertensive heart disease, or rheumatic mitral valve disease), thyrotoxicosis, alcohol abuse, pericarditis, PE, and postoperatively. Treatment • Pharmacologic Therapy. Intravenous adenosine, verapamil, digoxin, and beta- blockers (propranolol, metoprolol, and esmolol) can be used to slow down the ventricular response, and quinidine, procainamide, propafenone, ibutilide, and 19 FIGURE 19–8 Premature atrial contraction (PAC). The fifth beat is a PAC. 374 Clinician’s Pocket Reference, 9th Edition FIGURE 19–9 Paroxysmal atrial tachycardia. amiodarone can be used to maintain or convert to sinus rhythm (see individual agents in Chapter 21) • DC-Synchronized Cardioversion. Indicated if associated with increased myocar- dial ischemia, hypotension, or pulmonary edema (see Chapter 21, page 467) Atrial Flutter: Characterized by sawtooth flutter waves with an atrial rate between 250 and 350 bpm; the rate may be regular or irregular depending on whether the atrial impulses are conducted through the AV node at a regular interval or at a variable interval (Fig- ure 19–12). Example: One ventricular contraction (QRS) for every two flutter waves = 2:1 flutter. Clinical Correlations. Seen with valvular heart disease, pericarditis, ischemic heart dis- ease, pulmonary disease including PE, and alcohol abuse Treatment. Do NOT use quinidine or procainamide (atrial conduction may decrease to the point where 1:1 atrial:ventricular conduction can occur and the ventricular rate will in- crease and hemodynamic compromise can occur), otherwise, similar to treatment of atrial fibrillation. Ibutilide (a new Class III antiarrhythmic) is very effective. Nodal Rhythm AV Junctional or Nodal Rhythm: Rhythm originates in the AV node. Often associ- ated with retrograde P waves that may precede or follow the QRS. If the P wave is present, it is negative in lead II and positive in aVR (just the opposite of normal sinus rhythm) (Fig- 19 FIGURE 19–10 Multifocal atrial tachycardia. 19 Basic ECG Reading 375 FIGURE 19–11 Atrial fibrillation. ure 19–13). Three or more premature junctional beats in a row constitute a junctional tachy- cardia, which has the same clinical significance as PAT. Ventricular Arrhythmias PVC: As implied by the name, a premature beat arising in the ventricle. P waves may be present but have no relation to the QRS of the PVC. The QRS is usually >0.12 s with a left bundle branch pattern. A compensatory pause follows a PVC that is usually longer than after a PAC (Figure 19–14). The RR interval between beats 1 and 3 is equal to that between beats 3 and 5. Thus, the pause following the PVC (the fourth beat) is fully compensatory. The fol- lowing patterns are recognized: • Bigeminy. One normal sinus beat followed by

one PVC in an alternating fashion (Figure 19–15) • Trigeminy. Sequence of two normal beats followed by one PVC • Unifocal PVCs. Arise from one site in the ventricle. Each has the same configura- tion in a single lead. (See Figure 19–14.) • Multifocal PVCs. Arise from different sites; therefore, have different shapes (Figure 19–16) Clinical Correlations. PVCs occur in healthy persons and with excessive caffeine ingestion, anemia, anxiety, organic heart disease (ischemic, valvular, or hypertensive), secondary to medications (epinephrine and isoproterenol; from toxic level of digitalis and theophylline), 19 FIGURE 19–12 Atrial flutter with atrioventricular (AV) block (3:1 to 5:1 conduc- tion). 376 Clinician’s Pocket Reference, 9th Edition FIGURE 19–13 Junctional rhythm with retrograde P waves (inverted) following the QRS complex. or predisposing metabolic abnormalities (hypoxia, hypokalemia, acidosis, alkalosis, or hy- pomagnesemia) Criteria for Treatment. In the setting of an AMI: • >5 PVCs in 1 min (many clinicians would treat any PVC associated with an MI or injury pattern on ECG) • PVCs in couplets (two in a row) • Numerous multifocal PVCs • PVC that falls on the preceding T wave (R on T) Treatment. See also Chapter 21, page 459. • Lidocaine. Most commonly used; other antiarrhythmics include procainamide, and amiodarone. • Treatment of aggravating cause often sufficient (eg, treat hypoxia, hypokalemia, or acidosis) Ventricular Tachycardia: By definition, three or more PVCs in a row (Figure 19–17). Appears as a wide QRS usually with an LBBB pattern (as opposed to a narrow complex seen with supraventricular tachycardia). May occur as a short paroxysm or as a sustained run with a rate between 120 and 250 bpm. Can be life-threatening because of associated hy- potension and has a tendency to degenerate into ventricular fibrillation. Treatment of non- sustained ventricular tachycardia is controversial. 19 FIGURE 19–14 Premature ventricular contractions (PVCs). The fourth and eighth beats are PVCs. 19 Basic ECG Reading 377 FIGURE 19–15 Ventricular bigeminy. Clinical Correlations. See the section on PVCs. Patients with ventricular aneurysm are more susceptible to developing ventricular arrhythmias. Treatment. See Chapter 21, page 459. Ventricular Fibrillation: Erratic electrical activity from the ventricles, which fibrillate or twitch asynchronously. No cardiac output occurs with this rhythm (Figure 19–18). Clinical Correlations. One of two patterns seen with cardiac arrest (the other would be asystole or flat line) Treatment. See Chapter 21, page 252. Heart Blocks First-Degree Block: PR interval >0.2 s (or five small boxes). Usually not clinically significant (Figure 19–19). Drugs such as beta-blockers, digitalis, and calcium channel blockers (especially verapamil) can cause first-degree block. Second-Degree Block Mobitz Type I (Wenckebach). Progressive prolongation of the PR interval until the P wave is blocked and not followed by a QRS complex (Figure 19–20). May occur as a 2:1, 3:2, or 4:3 block. The ratio of the atrial:ventricular beats can vary. With a 4:3 block, every fourth P wave is not followed by a QRS. 19 FIGURE 19–16 Multifocal PVCs. The second, sixth, seventh, and ninth beats are PVCs. Only the second and sixth PVCs have the same morphology. 378 Clinician’s Pocket Reference, 9th Edition FIGURE 19–17 Ventricular tachycardia. Clinical Correlations. Seen with acute myocardial ischemia such as inferior MI, ASDs, valvular heart disease, rheumatic fever, or digitalis or propranolol toxicity. Can be transient. May progress to bradycardia (rare) Treatment. Usually expectant; if bradycardia occurs: atropine, isoproterenol, or a pace- maker Mobitz Type II. A series of P waves with conducted QRS complexes followed by a nonconducted P wave. The PR interval for the conducted beats remains constant. May occur as a 2:1, 3:2, or 4:3 block. The ratio of the atrial:ventricular beats can vary. With a 4:3 block, every fourth P wave is not followed by a QRS. (Note: AV block that is 2:1 can be either Mobitz type I or type II and may be difficult to differentiate. In general, Mobitz I has a pro- longed PR with a narrow QRS; Mobitz II has a normal PR interval with a bundle branch pat- tern [wide QRS]). Clinical Correlations. Implies severe conduction system disease that can progress into complete heart block. May be seen in acute anterior MI and cardiomyopathy. Treatment. Use of a temporary cardiac pacemaker, particularly when associated with an acute anterior MI Third-Degree Block: Complete AV block with independent atrial and ventricular rates. The ventricular rate is usually 20–40 bpm (Figure 19–21). Clinical Correlations. May occur as the result of degenerative changes in the conduc- tion system in the elderly, from digitalis toxicity, transiently with an acute inferior MI (due 19 FIGURE 19–18 Ventricular fibrillation. 19 Basic ECG Reading 379 FIGURE 19–19 First-degree AV block. The PR interval is 0.26 s. to temporary ischemia of the AV junction), and after acute anterior MI (much higher proba- bility of mortality than after inferior MI); can result in syncope or CHF Treatment. Usually requires placement of a temporary or permanent pacemaker BBB: Complete BBB is present when the QRS complex is >0.12 s (or three small boxes on the ECG strip). Look at leads I, V1, and V6. Degenerative changes and ischemic heart dis- ease are the most common causes. RBBB: The RSR′ pattern seen in V1 and or V2. Also a wide S in leads I and V6 (Figure 19–22) Clinical Correlations. May be seen in healthy persons but usually associated with dis- eases affecting the right side of the heart (pulmonary hypertension, ASD, or ischemia); sud- den onset is associated with pulmonary embolism or acute exacerbation of COPD. LBBB: The RR′ in leads I and/or V6. The QRS complex may actually be more slurred than double-peaked as in the RBBB. A wide S wave is seen in V1 (Figure 19–23). Clinical Correlations. Associated with organic heart disease (hypertensive, valvular, and ischemic) as well as severe aortic stenosis. Development of a new LBBB after an AMI may be an indication for inserting a temporary cardiac pacemaker. 19 FIGURE 19–20 Second-degree AV block, Mobitz type I (Wenckebach), with 4:3 conduction. 380 Clinician’s Pocket Reference, 9th Edition FIGURE 19–21 Third-degree AV block (complete heart block). The atrial rate is 100 bpm; the ventricular rate is 47 bpm. CARDIAC HYPERTROPHY Atrial Hypertrophy Atrial Hypertrophy: P wave >2.5 mm in height and >0.12 s wide (three small boxes on the ECG paper) RAE: Tall, slender, peaked P waves in leads II, III, aVF (may also be seen in V1 and V2. (Figure 19–24) Clinical Correlations. Seen with chronic diffuse pulmonary disease, pulmonary hyper- tension, and congenital heart disease (ASD) LAE: Notched P wave (“P mitral pattern”) seen in leads I and II. A wide (0.11 s or greater), slurred biphasic P in V1 with a wider terminal than initial component (negative de- flection) (Figure 19–25) Clinical Correlations. Seen with mitral stenosis or mitral regurgitation or secondary to LVH with hypertensive cardiovascular disease 19 I V1 V6 FIGURE 19–22 Leads I, V1, and V6 demonstrate the right bundle branch block (RBBB) pattern. 19 Basic ECG Reading 381 V6 V1 I FIGURE 19–23 Leads I, V1, and V6 demonstrate the left bundle branch block (LBBB) pattern. Ventricular Hypertrophy RVH: Tall R wave in V1 (R wave >S wave in V1), persistent S waves in V5 and V6, pro- gressively smaller R wave from V1 to V6, slightly widened QRS intervals (Figure 19–26), and strain pattern with ST-segment depression and T-wave inversion in V1 to V3. May also see a pattern of small R waves with relatively large S waves in V1 to V6. Invariably right axis deviation (>105 degrees) is present. Clinical Correlations. Associated with mitral stenosis, chronic diffuse pulmonary dis- ease, chronic recurrent PE, congenital heart disease (eg, tetralogy of Fallot), and biventricu- lar hypertrophy (VH and RVH, with LVH findings often predominating). II III 19 AVF V6 FIGURE 19–24 Right atrial enlargement, leads II, III, aVF, and V1. Note the tall P waves in II, III, and aVF and the tall slender P waves in V1. 382 Clinician’s Pocket Reference, 9th Edition V1 FIGURE 19–25 Left atrial enlargement. LVH: Voltage criteria (patients >age 35): S in V1 or V2 plus an R in V5 or V6 >35 mm, or R wave in aVL >11 mm, or R wave in I plus S wave in III >25 mm, or an R in V5 or V6 >26 mm. The QRS complex may be >0.10 s wide in V5 or V6. ST-segment depression and T-wave inversion in the anterolateral leads (I, aVL, V5, and V6) suggest LVH with strain (Figure 19–27). V1 V2 19 V3 V4 FIGURE 19–26 Right ventricular hypertrophy, leads V1, V2, V3, and V4. Note the tall R waves in V1 and V2, greater than the R waves in V3 and V4. 19 Basic ECG Reading 383 V1 V2 V5 V6 FIGURE 19–27 Left ventricular hypertrophy, leads V1, V2, V5, and V6. The S wave in the V2 + R wave in V5 is 55 mm. Note the ST changes and T-wave inversion in V5 and V6, suggesting “strain.” Clinical Correlations. Hypertension, aortic stenosis or insufficiency, long-standing CAD, and some forms of congenital heart disease MYOCARDIAL INFARCTION (See also Chapter 21, page 459.) 19 II III AVF FIGURE 19–28 ST-segment depression in leads II, III, and aVF in a patient with acute inferior subendocardial ischemia/infarction. 384 Clinician’s Pocket Reference, 9th Edition V4 V5 V6 FIGURE 19–29 ST elevation in leads V4, V5, and V6 in a patient with acute an- terolateral transmural ischemia/infarction. Myocardial Ischemia: Inadequate oxygen supply to the myocardium because of blockage or spasm of the coronary arteries. The ECG can show ST-segment depression (subendocardial ischemia) (Figure 19–28), ST elevation (transmural ischemia) (Figure 19–29), or symmetrically inverted (“flipped”) T waves (Figure 19–30) in the area of is- chemia (eg, inferior ischemia in II, III, and F; anterior ischemia in V1 to V6; lateral ischemia in I, aVL; anterolateral ischemia in I, aVL, V5, and V6; anteroseptal ischemia in V1, V2, V3, and V4. MI: Refers to myocardial necrosis caused by severe ischemia. Can be transmural (ST el- evation early, T-wave inversion, and Q waves late) or subendocardial (ST depression and T- wave inversion without evidence of Q waves). Table 19–1 outlines the localization of MIs. • Acute Injury Phase. Hyperacute T waves, then ST-segment elevation. Hyperacute T waves return to normal in minutes to hours. ST elevation usually regresses after hours to days. Persistent ST elevation suggests a left ventricular aneurysm. • Evolving Phase. Occurs hours to days after an MI. Deep T-wave inversion occurs and then replaces ST-segment elevation, and the T wave may return to normal. • Q Waves. Occur hours to days after a transmural MI. A Q wave is the initial negative deflection of the QRS complex. A “significant” Q wave is 0.04 s in duration and >25% the height of the R wave (Figure 19–31). May regress to normal after years. 19 V1 V2 V3 FIGURE 19–30 Inverted T waves. 19 Basic ECG Reading 385 V1 V2 V3 FIGURE 19–31 Q waves in leads V1, V2, and V3 in a patient with an acute an- teroseptal transmural myocardial infarction. Note the ST elevation in helping to de- termine the acute nature of the infarction. ELECTROLYTE AND DRUG EFFECTS Electrolytes Hyperkalemia: Narrow, symmetrical, diffuse, peaked T waves. With severe hyper- kalemia, PR prolongation occurs, the P wave flattens and is lost, and the QRS widens and can progress to ventricular fibrillation (Figure 19–32). Hypokalemia: ST-segment depression with the appearance of U waves (a positive de- flection after the T wave) (Figure 19–33) TABLE 19–1 Localization of Transmural Myocardial Infarction on ECG Location Presence of Q Wave or Reciprocal ST of MI ST-Segment Elevation Depression Anterior V1 to V6 (also poor R-wave II, III, aVF progression in leads V1 to V6)* Lateral l, aVL, V5, V6 V1, V3 Inferior II, III, aVF I, aVL, possibly an- terior leads Posterior Abnormally tall R and T waves in V1 to V3 V1 to V3 Subendocardial No abnormal Q wave. ST-segment elevation in the anterior, lateral, or 19 inferior leads *Normally in V1 to V6, the R-wave amplitude gradually increases and the S wave de- creases with a “biphasic” QRS (R = S) in V3 or V4. With an anterior MI, there will be a loss of R-wave voltage and the biphasic QRS will appear more laterally in V4 to V6, hence the term poor R-wave progression. 386 Clinician’s Pocket Reference, 9th Edition

V4 V6 AVF FIGURE 19–32 Diffuse tall T waves in leads V4, V6, and aVF with widened QRS and junctional rhythm (loss of P waves), representing hyperkalemia. Hypercalcemia: Short QT interval Hypocalcemia: Prolonged QT interval Drugs Digitalis Effect: Downsloping ST segment Digitalis Toxicity • Arrhythmias. PVCs, bigeminy, trigeminy, ventricular tachycardia, ventricular fibril- lation, PAT, nodal rhythms, and sinus bradycardia. • Conduction Abnormalities. First-degree, second-degree, and third-degree heart blocks Quinidine and Procainamide: With toxic levels, prolonged QT, flattened T wave, and QRS widening 19 II V2 V3 FIGURE 19–33 Leads II, V2, and V3 in a patient with hypokalemia. A U wave is easily seen in V2 and V3, but difficult to distinguish from the T wave in II. 19 Basic ECG Reading 387 I II III AVF V2 V3 V4 V5 V6 FIGURE 19–34 Acute pericarditis. MISCELLANEOUS ECG CHANGES Pericarditis: Diffuse ST elevation concave upward and/or diffuse PR depression and/or diffuse T-wave inversion (Figure 19–34) Clinical Correlations. Idiopathic, viral infections, as well as other infections, including bacterial, fungal, and TB, AMI, collagen–vascular diseases, uremia, cancer, Dressler’s syn- drome, and postpericardiotomy syndrome 19 FIGURE 19–35 Sinus bradycardia, J-point elevation with ST-segment elevation and prolonged QT interval (0.56 s) in a patient with hypothermia. 388 Clinician’s Pocket Reference, 9th Edition II AVF V3 FIGURE 19–36 Short PR interval and delta waves in leads II, aVF, and V3 in a pa- tient with Wolff–Parkinson–White syndrome. Hypothermia: Sinus bradycardia, AV junctional rhythm, or ventricular fibrillation com- mon. Classically, J point (the end of the QRS complex and the beginning of the ST segment) elevated and an intraventricular conduction delay and a prolonged QT interval possible (Fig- ure 19–35) WPW Syndrome: A preexcitation syndrome caused by conduction from the SA node to the ventricle through an accessory pathway that bypasses the AV node. Classically, a short PR interval occurs along with a delta wave (a delay in the initial deflection of the QRS complex). Clinically, these patients commonly have tachyarrhythmias, such as atrial fibrilla- tion (Figure 19–36). 19 20 CRITICAL CARE Treatment of the Critically Ill Patient Indications for Intubation ICU Progress Note Mechanical Ventilators Cardiovascular System Specific Problems in Critically Ill Cardiovascular Physiology Patients Central Venous Pressure Quick Reference to Critical Care Pulmonary Artery Catheters Formulas/ICU Formulas Determinations of Cardiac Output Guidelines for Adult Critical Care Drug Shock States Infusions Clinical Pulmonary Physiology TREATMENT OF THE CRITICALLY ILL PATIENT Patients in the ICU setting typically have multisystem disease or injuries. The interactions between different dysfunctional organ systems is complicated and often overwhelming for the student or junior house officer. This chapter describes a system-by-system approach to dealing with the critically ill pa- tient. This approach forces the clinician to focus sequentially on each major organ system and to evaluate each system’s function and interaction with other organ systems. This ap- proach also allows the physician to integrate abnormalities within each system into a strat- egy for treating the patient as a whole. A complete but concise daily progress note will document this critical evaluation and integration process. ICU PROGRESS NOTE The ICU progress note is a concise, well-organized means of documenting the events of the past 24 h. The organization of a daily progress note is outlined here. The most important parts of this note are the assessment and the plan. Although the collected data can be found elsewhere in the chart, the physician’s written assessment and interpretation of these data and events communicate the medical decision-making process to all who read the chart. A simple organizational approach to the daily ICU progress note: A. Outline the patient’s problem list and/or injury summary. 20 1. Include all active problems, major inactive problems, significant past medical his- tory. B. Outline events and procedures of the past 24 h. C. List current medications. D. Flow sheet data. 389 Copyright 2002 The McGraw-Hill Companies, Inc. Click Here for Terms of Use 390 Clinician’s Pocket Reference, 9th Edition 1. Include vital signs, pulmonary artery catheter data, ventilator settings, laboratory and culture data. 2. Also include radiographic data. E. List physical exam findings. F. Provide impression and assessment. Each of the following systems should be addressed daily. 1. Neurologic function 2. Pulmonary function, including mechanical ventilator 3. Cardiovascular function 4. Gastrointestinal function 5. Genitourinary function 6. Metabolic and nutritional status 7. Hematologic function 8. Infectious disease status 9. Prophylaxis (ie, DVT, ETOH, stress ulcer, etc) With each of the areas listed in item 9, try to anticipate and avoid complications G.Outline therapeutic plan for the day. The following is an example of an ICU progress note that uses this approach. It is written for a trauma patient but can easily be modified for any clinical setting. Sample ICU Progress Note PROBLEM LIST: • S/P MVA • Left pulmonary concussion • Left hemopneumothorax S/P left chest tube • Grade 4 splenic injury S/P splenectomy • Acute renal failure • ARDS • Complex past medical history: Hypertension Gout • Allergic: Morphine sulfate EVENTS OF PAST 24 HOURS: • Increasing FiO2 and PEEP • Renal Consult CURRENT MEDICATIONS • Dopamine • Fentanyl infusion • Ativan infusion 20 • Pepcid • Vancomycin FLOW SHEET DATA: • P 150 (NSR), BP 110/65, I/O: 3400/2210, (continued ) 20 Critical Care 391 Sample ICU Progress Note (continued) • PAP 45/20, PCWP 14, CO 3.78, CI 2.54, EDVI 89 • Ventilator Setting: SIMV rate 16/4, 75%, PEEP 12, PS 10 • Lab data: Hct 30%, WBC 17.5 PHYSICAL EXAM: • Neurologic: Intubated, sedated, moves all 4 extremities to painful stimuli • HEENT pupil equal and reactive EOM intact • Neck immobilized • Cardiovascular: RRR, no increased JVD, 2+ capillary refill, toes warm • Pulmonary: Coarse BS bilat., decreased on left. Chest tube in place • Gastrointestinal: Midline incision healing well, soft, nondistended, no guarding, + bowel sounds • Extremities: Warm well perfused ASSESSMENT: • Neurologic: Stable, continue sedation while on ventilator. • Cardiovascular: Continues to require intermittent fluid challenge to main- tain BP, this may be the cause of acute renal failure. Will continue fluids and may add dopamine to improve CO. • Pulmonary: Worsening FiO2 and PEEP requirements overnight, likely ARDS complicated by pulmonary contusion. Will obtain CXR this AM and wean FiO2 and increase PEEP as tolerated by BP and CO. • Gastrointestinal: S/P splenectomy, ileus continues, will place feeding tube today. • Renal: Acute renal failure continues. Will proceed with renal ultrasound to R/O postrenal cause. • Hematologic: S/P splenectomy HCT stable, will give postsplenectomy vaccines. Abbreviations: See Abbreviations list at the beginning of the book. CARDIOVASCULAR SYSTEM Cardiovascular instability is one of the most common problems faced in the ICU. Under- standing the approach to the evaluation of the cardiovascular system is essential to treating any critically ill patient. Inspection Inspection of the cardiovascular system is divided into three main areas: 20 Jugular Venous Distention • Daily examination of the patient in the ICU should include examination of neck veins to look for JVD. A patient sitting at a 45-degree angle who has distended neck veins has a CVP of 12–15 cm H2O or higher. 392 Clinician’s Pocket Reference, 9th Edition • Distended neck veins in the face of systemic hypotension in the acutely ill or injured patient suggest: Tension pneumothorax Pericardial tamponade Cardiac dysfunction Precordial Contusion • Bruising of the anterior chest wall is commonly associated with blunt trauma from a steering wheel. Such an injury pattern should alert the physician to the possibility of a myocardial contusion. Treatment of this condition consists of continuous ECG monitoring and vigorous correction of arrhythmias. Extremity Perfusion • Check all four extremities for distal perfusion, including pulses, color, temperature, and capillary refill. • Pay special attention to the following areas: Sites distal to long bone fractures or dislocations Sites distal to indwelling arterial catheters Blood Pressure Blood pressure over the short term is considered adequate if renal perfusion is maintained. In a young, previously healthy individual, an adequate BP usually corresponds to a MAP of greater than 70 mm Hg. Technical Tip: If the cuff is too small an obese arm will give a systolic BP 10–15 mm Hg higher than the actual pressure. Systolic Hypertension: A systolic blood pressure >140 mm Hg with a normal diastolic pressure. In the acute care setting, systolic hypertension is thought to be secondary to in- creased cardiac output. Systolic hypertension is seen in the following situations: • Generalized response to stress • Pain • Thyrotoxicosis • Anemia Diastolic Hypertension: A diastolic pressure >90 mm Hg. Isolated diastolic hypertension is associated with three general disease categories: • Renal disease • Endocrine disorders • Neurologic disorders Treatment of Hypertension: Hypertension is of concern in the ICU when confronting a new MI or a vascular anastomosis and especially following carotid artery surgery. Ideally, 20 the systolic blood pressure in this instance is maintained above 130 and below 160. A sys- tolic pressure >180 mm Hg usually requires immediate treatment. Several drugs are com- monly used to treat acute hypertension in the ICU setting. These include nitroprusside (Nipride), hydralazine (Apresoline), labetalol (Normodyne), a beta-blocker, or nitroglycerin. Beta-blockade should be used with Nipride in treating hypertension associated with an 20 Critical Care 393 aortic aneurysm. The emergency management of hypertension is discussed in Chapter 21, page 470 and the specific agents are discussed on page 439 and in Chapter 22. Pulse Pressure Pulse pressure is the difference between systolic and diastolic blood pressures. Wide Pulse Pressure: A pulse pressure >40 mm Hg. A wide pulse pressure is associated with: • Thyrotoxicosis • Arterial venous fistula • Aortic insufficiency Narrow Pulse Pressure: A pulse pressure <25 mm Hg. A narrow pulse pressure is associated with: • Significant tachycardia • Early hypovolemic shock • Pericarditis • Pericardial effusion or tamponade • Ascites • Aortic stenosis Mean Arterial Blood Pressure MAP is calculated by taking the diastolic pressure plus one third of the pulse pressure. MAP is used to calculate several other hemodynamic variables. Paradoxical Pulse: Paradoxical pulse is a function of the change in intrathoracic pres- sures during inspiration and expiration. Normally, systolic blood pressure falls between 6 and 10 mm Hg with inspiration. This fall is reflected by a systolic blood pressure that varies with respiration. If this variation occurs over a range >10 mm Hg, the patient is said to have a paradoxical pulse (Figure 20–1). For the technique to measure the paradoxical pulse, see Chapter 13, page 298. Conditions associated with a paradoxical pulse: • Pericardial tamponade • Asthma and COPD • Ruptured diaphragm • Pneumothorax Heart Murmurs Monitor the ICU patient for the development of a new murmur. Murmurs are classically de- scribed as systolic or diastolic. All new murmurs should be characterized by their intensity, location, and variation with position and respiration. Diastolic murmurs are practically al- ways pathologic. Details on heart murmurs can be found in Chapter 1, page 14. Systolic Murmurs: Abrupt onset caused by conditions that have clinical significance 20 for the acutely ill patient: 1. Papillary muscle injury. Papillary muscle dysfunction following AMI is characterized by an apical systolic murmur. The injury to the papillary muscle may cause a murmur 394 Clinician’s Pocket Reference, 9th Edition Paradoxical pulse >10 mm Hg Normal respiratory variation <10 mm Hg Systolic BP (mm Hg) Diastolic Expiration Inspiration FIGURE 20–1 The paradoxical pulse. of grade I–II/VI. After rupture of the papillary muscle, a sudden pansystolic murmur of grade II–IV/VI may appear. The diagnosis of papillary muscle rupture can be made ei- ther at cardiac catheterization or by echocardiography. 2. Intraventricular septum rupture. May be indicated by the appearance of a loud sys- tolic murmur of abrupt onset. A catastrophic event that may follow MI. Usually accom- panied by massive pulmonary edema. This situation is an indication for emergency cardiac catheterization. Diastolic Murmurs: The major concern is the appearance of a diastolic murmur in the acutely injured patient is bacterial endocarditis, an entity that is becoming more common in patients who are treated in ICUs for long periods. Foreign bodies, such as central venous lines, hyperalimentation lines, and pulmonary artery catheters, all contribute to the increas- ing incidence of bacterial endocarditis. 1. Gallop. Defined as three sequential heart sounds in which the first two beats of the triplet are closer together than the third. The result is a sound that resembles the gallop of a horse. A newly occurring

gallop may herald the onset of one or more of the following: • MI • Severe CHF • Mitral regurgitation secondary to injury of the papillary muscle 20 • Anemia 2. Pericardial friction rub. Classically described as the sound of two pieces of leather rubbing together. Frequently high pitched and may be intermittent. Common following open heart surgery (in this setting, does not necessarily indicate pathologic changes). 20 Critical Care 395 Development of a pericardial friction rub should cause one to suspect one of the following: • Pericarditis • Pericardial effusion • MI near the surface of the pericardium CARDIOVASCULAR PHYSIOLOGY Prior to a discussion of central venous pressure and pulmonary artery catheters, a brief re- view of cardiovascular physiology may be helpful. Definitions Cardiac Output: Defined as the quantity of blood pumped by the heart each minute. Normal output in an adult is 3.5–5.5 L/min. Cardiac Index: Used to compensate for body size. Defined as the CO divided by the patient’s body surface area. The normal CI is 2.8–3.2 L/min/m2. A CI of <2.5 requires im- mediate assessment and treatment. Determinants of Cardiac Output Cardiac output is determined by heart rate and stroke volume. Stroke volume depends on the following: • Preload • Afterload • Contractility Preload: The initial length of the myocardial muscle fiber is proportional to the left ven- tricular end-diastolic volume. As the volume of blood remaining in the heart after each beat (end-diastolic volume) increases, the stretch on individual myocardial muscle cells in- creases. As the stretch increases, the energy of contraction increases proportionally until an optimal tension develops. Starling’s Law: When the myocardial muscle cell is stretched, the developed tension in- creases to a maximum and then declines as the stretch becomes more extreme (Figure 20–2). Afterload: Defined as the resistance to ventricular ejection. Measured clinically by the calculation of SVR. Contractility: The ability of the heart to alter its contractile force and velocity indepen- dent of fiber length. In simple terms, it represents the intrinsic strength of the individual muscle fiber cells. Contractility can be increased by stimulation of beta-receptors in the heart (see below). Brief Review of the Adrenergic, or Sympathetic Nervous System Cardiac output and its determinants (preload, afterload, and contractility) are all influenced 20 by the adrenergic nervous system. The adrenergic system releases catecholamines (epineph- rine and norepinephrine), which bind to end-organ receptors. These adrenergic receptors are divided into two classes, designated alpha (α) and beta (β), and their actions are summa- rized in Table 20–1. 396 Clinician’s Pocket Reference, 9th Edition Cardiac * index Supraoptimal tension/ diminished cardiac output PCWP * Cardiac index Optimal tension/ optimal cardiac output PCWP Cardiac index * Suboptimal tension/ diminished cardiac output PCWP 20 FIGURE 20–2 Representation of Starling’s law. PCWP = pulmonary capillary wedge pressure. 20 Critical Care 397 TABLE 20–1 Adrenergic Receptors and Their Actions in the Cardiovascular System Receptor Site Action Beta-1 Myocardium Increased contractility SA node Increased heart rate Beta-2 Arterioles Vasodilatation Lungs Bronchodilatation Alpha Peripheral Vasoconstriction arterioles Alpha-1 Receptors: Adrenergic receptors found primarily in the peripheral arterial sys- tem. When stimulated, these receptors cause vasoconstriction and increase BP, SVR, and afterload. Beta-1 Receptors: Found primarily on the SA node of the heart. When activated, these receptors stimulate the SA node to increase the heart rate and increase contractility. This in- creases CO and BP. Beta-2 Receptors: Found in the peripheral vascular tree as well as in the bronchial wall smooth muscle. Activation causes vasodilation of the peripheral vasculature and bronchodi- latation. Hemodynamically, this decreases SVR, BP, and afterload. These adrenergic receptors are important because many of the cardiovascular drugs used in the ICU act through their sympathomimetic properties. These drugs usually have specific receptor affinity (ie, β versus α) and consequently differ in their effects. Drugs that act on alpha-1 receptors, for example, are called “vasopressors” because they cause vaso- constriction. Drugs that act on beta-1 receptors are conversely called “inotropes” because they increase contractility and heart rate. Commonly used sympathomimetics are listed in Table 20–2. A guide to administration of these agents appears in Table 20–10. CENTRAL VENOUS PRESSURE The CVP catheter is one of two major devices used in cardiovascular instrumentation. The other major device, the pulmonary artery catheter (often called the Swan–Ganz catheter), is considered in the next section. The CVP reading reflects the right ventricular filling pressure. This filling pressure de- fines the ability of the right side of the heart to accept and pump blood. Method 20 A 14-gauge intravenous catheter is inserted into the internal jugular or subclavian vein (see Chapter 13). A pressure transducer connected to the monitor provides the recordings. A chest x-ray is required to confirm the position of the catheter in the superior vena cava. The zero point for the manometer is usually 5 cm below the sternal notch, in the midaxillary line. 398 Clinician’s Pocket Reference, 9th Edition TABLE 20–2 Actions of Sympathomimetic Drugs Effect on Drug Beta-1 Beta-2 Alpha Dopamine ++++ ++ ++++ Dobutamine ++++ ++ + Isoproterenol ++++ +++ 0 Norepinephrine ++ 0 ++++ Phenylephrine 0 0 ++++ Epinephrine ++++ ++ ++++ Key: + = Relative effect; 0 = no clinically significant effect. Implications More important than the actual isolated measurements of CVP are the relative changes that take place as a patient’s fluid or cardiac status changes. Therefore, serial readings are made. The implications of CVP readings are given in Table 20–3. CVP Limitations • CVP does not reflect total blood volume or left ventricular function. • CVP will be altered by changes in pulmonary artery resistance and compliance of the right ventricle. • Use may be limited by changes in intrathoracic pressure, such as those that occur during positive pressure ventilation or pneumothorax or in the presence of tumors. • CVP may be normal in the face of sepsis or hypovolemia accompanied by compro- mised myocardial function. TABLE 20–3 Interpretation of CVP Readings Reading (cm H20) Description Implications <4 Low Fluids may be pushed 4–10 Midrange Not clinically useful >10 High Suspect CHF, cor pulmonale, COPD, ten- 20 sion pneumothorax, cardiac tamponade Abbreviations: CVP = central venous pressure; CHF = congestive heart failure; COPD = chronic obstructive pulmonary disease. 20 Critical Care 399 • Occult left ventricular failure may occur in the presence of normal CVP. • Patients with COPD may require an elevated CVP to optimize their cardiac output. • Pulmonary artery catheter readings are more accurate measurements of a patient’s fluid and cardiac status than is the CVP. Technical Tips • If CVP readings do not fluctuate with respiration, the readings are inaccurate. • If appropriate, remove the patient from the ventilator when taking a CVP reading. • Have the head of the bed flat when taking readings, so that serial readings are com- parable. • Always use the same zero point (5 cm below the sternum in the midaxillary line) so that serial readings are comparable. PULMONARY ARTERY CATHETERS The pulmonary artery (PA or Swan–Ganz) catheter is a device that allows the measurement of central circulatory parameters useful in the treatment of the acutely ill patient. Volume status, vascular tone (both pulmonary and peripheral), and the heart’s pumping ability are all monitored with the PA catheter. The catheter actually passes through the heart; its distal end is in the pulmonary artery (Figure 20–3). It allows the measurement of the pulmonary artery pressure (PAP), the pulmonary artery occlusion pressure (PAOP, also known as the pul- monary capillary wedge pressure, PCWP), the CO, and the CVP. Newer technology also al- lows for the continuous monitoring of mixed venous oxygen saturation (SvO2), measurement of the right ventricular ejection fraction (REF), and the right ventricular end- diastolic volume index (RVEDVI). Indications Common clinical conditions requiring PA catheter monitoring include: • Acute heart failure • Complex circulatory and fluid conditions (massive resuscitation) • Shock states • Diagnosis of pericardial tamponade • Intraoperative management (aneurysm repair, elderly patient undergoing major surgery) • Complicated MI Catheter Description The original PA catheter, still commonly called the Swan–Ganz catheter after its inventors, consists of three lumens and a thermistor at the tip (Figure 20–4). It is typically marked in 10-cm increments and is radiopaque. Lumens 20 • Balloon port. Usually a square white port that inflates the balloon at the tip of the catheter. Inflation of the balloon requires between 1 and 1.5 mL of air. • Proximal port. Located approximately 30 cm proximal to the tip, it lies in the supe- rior vena cava. May be used for the administration of routine IV fluids when not being used in determinations of CO. 400 Clinician’s Pocket Reference, 9th Edition Pulmonary artery Superior vena cava Pulmonary artery catheter FIGURE 20–3 Relative positioning of the pulmonary artery catheter. • Distal port. Lies in the pulmonary artery beyond the balloon. This port is attached to 20 a pressure transducer that provides continuous PAP tracings and allows intermittent PAOP monitoring. Thermistor. A temperature sensor. Provides continuous measurements of core temperature as well as measurements used in the thermal dilation method for determination of CO. (This method is described later in this chapter.) 20 Critical Care 401 Modifications of Pulmonary Artery Catheter: Several modifications of the origi- nal Swan–Ganz catheters allow for additional functions and measurement capabilities. These modifications include additional ports for administration of IV medication or par- enteral nutrition. • Pacing Swans have extra ports (approximately 19 cm from the tip) through which pacing wires are passed into the right ventricle. Other models contain electrodes along the surface of the catheter, capable of pacing both the right atrium and ven- tricle. • Oximetric PA catheter includes the standard ports of the Swan–Ganz type with fiberoptic components that emit light impulses to and from the distal end of the catheter. These light impulses are then reflected back by hemoglobin to monitors that continuously calculate O2 saturation (See Figure 20–4). • Right ventricular ejection catheter is capable of determining the right ventricular ejection fraction, which is then used to calculate the EDVI. The EDVI is the best in- dicator of preload in the shock state. Thermistor/ fiberoptic port Distal port Proximal port Thermistor port Balloon port Transmitting fiberoptic channel Receiving fiberoptic channel Distal port 20 FIGURE 20–4 An example of a pulmonary artery catheter. This one features an oximetric measuring feature (see text for a complete description). 402 Clinician’s Pocket Reference, 9th Edition Contraindications: If a PA catheter is needed to treat a patient in a critical care setting, there are no absolute contraindications. Patients with LBBB may experience complete heart block and may require placement of a temporary pacemaker prior to catheter placement. As with all indwelling catheters that are frequently manipulated, PA catheters increase the risk of infection. Materials: In most institutions, a single brand of a flow-directed, balloon-tipped PA catheter is available (See Figure 20–4). An insertion kit provides the catheter as well as an introducer sheath; flexible J-tip guidewire; vessel dilator; catheter contamination shield; and the various syringes, needles, preparation material, local anesthetic, and other items needed to insert the catheter (Figure 20–5). The monitoring system (transducers, pressure tubing, stopcocks) and heparinized, pressurized flush system are usually set up by the nursing staff. Pulmonary Artery Catheterization Procedure 1. Informed consent is usually required. The patient should be closely monitored with an ECG. Emergency resuscitation medications must be on hand in the event of an arrhyth- mia. 2. Choose a site and prep and drape the area. A widely draped field is needed because of the length of the tubing and guidewire. The choice of site is dictated by patient vari- ables and operator experience. The easiest sites to place a PA catheter without fluoro- scopic guidance are the right internal jugular vein and the left subclavian vein. In a patient who may receive thrombolytic therapy or who has a coagulopathy, femoral and median basilic veins are better routes. 3. Use a strict sterile approach with gown, gloves, and mask. Vessel dilator Flexible “J” tip Catheter contamination shield Spring wire guide Percutaneous sheath introducer Side port Catheter Hemostasis for blood port valve sampling or infusion 20 FIGURE 20–5 Additional items used for pulmonary artery catheter placement. (Reprinted, with permission, from: Chesnutt MS, et al [eds]: Office & Bedside Proce- dures. Appleton & Lange, Stamford CT, 1992.) 20 Critical Care 403 4. Prepare the PA catheter by attaching it to the

monitor and flushing the lumens with he- parinized saline solution (1 mL of 1:100 U heparin in 10 mL of NS). Check the bal- loon’s function, and gently tap the catheter to ensure that an appropriate waveform is present on the monitor. Set the pressure transducer level to the middle of the patient’s chest. This is approximately the level of the left atrium (midpoint of the chest wall at the fourth intercostal space). Some clinicians advocate checking the balloon for leaks by placing it in a container of sterile saline. Note: Never fill the balloon with fluid; use air or CO2. The volume is typically 1–1.5 mL, depending on the catheter size. Place the catheter through the contamination shield and lay it on the sterile field. 5. The central vein is cannulated. (See Central Venous Catheterization, Chapter 13, page 253, for details.) Pass the flexible end of the J-wire (standard size is 45 cm long and 0.035 in. in diameter) into the vein through the needle. In general, never push a guidewire where it does not want to go and always keep one hand on the guidewire. Make sure the flexible tip is passed, not the more rigid end. The stiff end can more eas- ily perforate a vessel. 6. Mount the introducer sheath on the vessel dilator. Pass the guidewire through the vessel dilator. If the skin site is insufficient, nick it with the No. 11 blade provided in the set. 7. Pass the vessel dilator into the vessel first. A slight twisting motion may be necessary to then advance the sheath into the vessel (Figure 20–6). Slowly remove the guidewire and the vessel dilator. Most PA catheter sheaths have a hemostatic valve mechanism that prevents air from entering the central system and blood from pouring out. If no valve mechanism is present, place a finger over the end of the sheath to prevent exces- sive blood loss or air embolization. It is handy to mount a syringe on the side port to as- pirate blood to confirm proper intravascular positioning of the sheath. After the position is confirmed, flush with heparinized flush solution. Vessel dilator Guidewire Percutaneous sheath introducer 20 FIGURE 20–6 The introducer sheath and the vessel dilator are passed into the vessel. (Reprinted, with permission, from: Chesnutt MS, et al [eds]: Office & Bedside Procedures. Appleton & Lange, Stamford CT, 1992.) 404 Clinician’s Pocket Reference, 9th Edition 8. Once the sheath is in place, the prepared catheter (fluid-filled, contamination sheath in place) can be advanced into the sheath (Figure 20–7). Once you have advanced it ap- proximately 15 cm, the balloon will clear the tip of the sheath and can be gently in- flated with 1.5 mL of air, using the volume-limiting syringe provided with the set (for a No. 7 or 7.5 French catheter). The maximum amount of air to be used with smaller catheters (No. 5 French) is 1.0 mL. If you encounter resistance to full inflation, con- sider that the balloon may not have yet cleared the sheath or that it may be in an ex- travascular location. 9. Once the balloon is inflated, advance the catheter to the level of the right atrium under the guidance of the pressure waveform and the ECG. Monitor the waveform and ECG at all times while advancing the balloon catheter. Figure 20–8 displays the normal pres- sures that can be seen as the catheter is advanced. Advance the catheter with the bal- loon inflated, and withdraw it with the balloon deflated. PA catheters usually come with a preformed curve on the tip. The catheter should be inserted pointing the catheter tip anteriorly and to the left. Positioning in the right atrium is probably best determined by watching for the characteristic waveform. The right atrium is generally located ap- proximately 20 cm from the right internal jugular or subclavian vein insertion site and approximately 25–30 cm from the left subclavian vein insertion site. Advance the catheter steadily. An abrupt change in the pressure tracing occurs as the catheter enters the right ventricle. There is generally little ectopy on entry into the right ventricle; how- ever, as the catheter advances into the right ventricular outflow tract, PVCs may occur. Keep advancing the catheter until the ectopy disappears and the pulmonary artery trac- ing is obtained. If this does not occur, deflate the balloon, withdraw the catheter, and Swan–Ganz catheter Catheter contamination shield 20 FIGURE 20–7 The fluid-filled pulmonary artery catheter is passed into the intro- ducer sheath. (Reprinted, with permission, from: Chesnutt MS, et al [eds]: Office & Bedside Procedures. Appleton & Lange, Stamford CT, 1992.) 20 Critical Care 405 Balloon port Distal lumen Pulmonary Proximal arteries lumen Superior Wedged vena position cava RA RV A Time breaks 40 30 20 10 RA RV PA Wedge B 20 FIGURE 20–8 Positioning and pressure waveforms seen as the pulmonary artery catheter is advanced. (Reprinted, with permission, from: Haist SA, et al [eds]: Inter- nal Medicine on Call, 2nd ed. Appleton & Lange, Stamford CT, 1996.) 406 Clinician’s Pocket Reference, 9th Edition make another attempt with the balloon inflated after slightly rotating the catheter. Ob- tain the PCWP after advancing the catheter another 10–15 cm. The catheter’s final po- sition should be such that the PCWP is obtained with full balloon inflation and the PAP tracing is present with the balloon deflated. In the “ideal position,” transition from PAP to PCWP (and vice versa) occurs within three or fewer heart beats. In an adult, the typi- cal length to the pulmonary artery position is 40–45 cm. Never withdraw the catheter with the balloon inflated. (See Figure 20–8 for normal waveforms seen as the catheter is advanced. Table 20–4 shows normal PA catheter measurements.) 10. Once the position is acceptable, lock the contamination shield onto the sheath. This al- lows readjustment of the catheter should this be necessary after the sterile field is taken down. Suture the sheath (using 3-0 or 4-0 nylon on a cutting needle), suture or secure the catheter in place and dress according to your institution’s practice (often with a transparent dressing), and connect fluid to the inflow port on the sheath. This inflow port on the sheath can be used for IV fluid and some medication administration. Obtain a chest x-ray to document the catheter’s present position as well as to rule out a pneu- mothorax or other complication from central venous catheterization. A properly posi- tioned catheter should lie just beyond the vertebral bodies in the nonwedged position. 11. Common problems. Catheter placement is much more difficult if severe pulmonary artery hypertension is present. If there is significant cardiac enlargement, particularly dilation of the right heart structures, the catheter may have a propensity to coil and get lost in its path to the right ventricular outflow tract. Fluoroscopy may be required to get the catheter into the correct position and it will hold this position poorly. Placement of the catheter in the pulmonary artery may also be difficult in the setting of a low cardiac output because the balloon-tipped catheter depends on blood flow to carry it through the right heart chambers. 12. Cardiac output can be measured by thermal dilution. First, connect the thermistor to the cardiac output computer. Then rapidly inject fluid (usually 10 mL of ice-cooled NS) through the right atrial port. Have someone set the computer as you inject. The com- puter displays the CO. Repeat two more times. If all of these values are approximately the same, then average the readings and record. Newer continuous cardiac output moni- toring PA are available in some units (see pages 401 and 412). For normal cardiac out- put and index, see Table 20–4. Complications 1. Most complications that occur in the course of PA catheterization are related to central vein cannulation and include arterial puncture, placement of the wire or catheter in the extravascular space, and pneumothorax. 2. Arrhythmias are another common complication. The most common of these are tran- sient PVCs that occur when the catheter is advanced into the right ventricular outflow tract. If a patient with a PA catheter suddenly develops frequent premature ventricular complexes, displacement of the catheter should be suspected. 3. VT and VF are rare occurrences. 4. Transient RBBB occurs occasionally as the catheter passes through the right ventricu- 20 lar outflow tract. In a patient with preexisting LBBB, this can result in complete heart block. In this setting, some form of backup pacing should be readily available. Com- plete heart block has been reported but occurs rarely. 5. Significant pulmonary infarcts and pulmonary artery rupture are serious but infrequent complications of PA catheters secondary to permanent wedge or peripheral placement of the catheter. 20 Critical Care 407 TABLE 20–4 Normal Pulmonary Artery Measurements Parameter Range Right atrial pressure 1–7 mm Hg Right ventricular pressure Systolic 15–25 mm Hg Diastolic 0–8 mm Hg PAP Systolic 15–25 mm Hg Diastolic 8–15 mm Hg Mean 10–20 mm Hg PCWP (PAOP) 6–12 mm Hg Cardiac output 3.5–5.5 L/min Cardiac index 2.8–3.2 L/min/m2 Mixed venous O2 saturation (SvO2) 70–80% Right ventricular ejection fraction 80–120 mL Abbreviations: PAP = pulmonary artery pressure; PAOP = pulmonary artery occlusion pressure; PCWP = pulmonary capillary wedge pressure. 6. Most complications and problems tend to increase with the time the catheter is in place. The risk of bacteremia and SBE is significant in severely ill patients receiving chronic instrumentation. In the setting of unexplained fever, the catheter and sheath should al- ways be removed and cultured. The catheter and sheath should be replaced at a differ- ent site if a pulmonary catheter is still indicated. Pulmonary Artery Catheter Measurements Pulmonary Artery Pressure: Measured when the PA catheter is in its resting position in the pulmonary artery (balloon deflated). Measures both systolic pulmonary artery pres- sure and diastolic pulmonary artery pressure. Pulmonary Artery Occlusion Pressure: (also called the “pulmonary capillary wedge pressure,” or “wedge pressure”). A reflection of the left atrial pressure. Measured when the balloon at the tip of the PA catheter is slowly inflated with air (maximum 1.5 mL) and carried out, by blood flow, into one of the smaller branches of the pulmonary artery. The balloon must be deflated after each PAOP measurement to avoid pulmonary infarction. In the absence of mitral valvular disease, PAOP correlates closely with the LAP and with the left ventricular end-diastolic pressure. This correlation exists because of the unobstructed continuity between the pulmonary artery and the left side of the heart. As a result of this continuity, the PAOP can never be greater than the PAD. If the LVEDP increases, this should be reflected by an increase in PAOP, which, in turn, increases the PAD. Therefore, if a PA 20 catheter monitor shows a wedge pressure higher than the PAD pressure, a technical error must exist. This is an important method to check the accuracy of the PAOP. Left Ventricular End-Diastolic Pressure: LVEDP is a measure of preload and is used to guide fluid resuscitation and optimize cardiac output. Recall that to optimize stroke 408 Clinician’s Pocket Reference, 9th Edition volume on the Starling curve, the preload must be adequate to stretch the wall of the left ventricle. Too little volume (hypovolemia) results in too little tension and therefore a de- creased CO. Conversely, too much preload volume causes overstretching beyond the point of maximum tension and causes a decrease in CO. Clinically, the PAOP is used to keep pre- load in an optimum range to maximize stroke volume. The normal PAOP varies between 6 and 12 mm Hg, but may be higher for different disease states. Right Ventricular Ejection Fraction, Right Ventricular End-Diastolic Volume Index: A rapid-response thermistor and the cardiac output computer are used to calculate the REF. Once REF and CO are known, the EDVI can be calculated. The EDVI is another measure of preload, and it allows a more accurate assessment of volume status regardless of pulmonary status. For example, a patient with severe ARDS may have markedly elevated peak inspiratory pressures. Although the CVP and PAOP may be falsely elevated, the EDVI is measuring a volume, not a pressure, allowing a more precise determination of volume sta- tus across a wide variety of clinical situations. The normal range for EDVI is 80–120 mL. Differential Diagnosis Table 20–4 shows normal pulmonary artery measurements

(see also Figure 20–8), and the differential diagnosis based on these and other critical care parameters is shown in Table 20–5. Clinical Applications The PA catheter allows the clinician to measure a patient’s volume status and myocardial performance. As stated earlier, myocardial performance or CO depends on heart rate and stroke volume. Stroke volume is, in turn, dependent on preload, afterload, and contractility. Heart Rate: Heart rate, in addition to stroke volume, determines the cardiac output. The body increases the HR to increase CO in the face of inadequate perfusion. Hence, tachycar- dia is an additional indicator of O2 delivery/demand imbalance. Tachycardia >120 bpm in- creases myocardial O2 demand significantly and should be promptly treated. The PA catheter allows the establishment of adequate myocardial filling pressures such that the HR may be clinically manipulated to maximize CO. In a patient with adequate filling pressures, slow HR (<80 bpm), and a low CO, drugs that speed up the heart (called “chronotropes”) may be used to increase CO. Alternatively, tachycardia >120 bpm with an adequate PAOP may be pharmacologically slowed to decrease the strain on the heart. Preload (Stroke Volume): Indicated by the PAOP or EDVI, a reflection of left ventric- ular end-diastolic volume. In simple terms, preload is the amount of blood in the heart prior to contraction. Consequently, preload represents the stretch placed on the individual my- ocardial cell. When the PAOP is optimized, myocardial performance is optimized according to the Starling curve. 1. Clinical implications in a healthy heart. A low PAOP or EDVI means suboptimal myocardial muscle tension and, consequently, suboptimal myocardial performance. Cardiac output may be increased by the administration of fluids. The result is an in- 20 crease in left ventricular end-diastolic volume, an increase in myocardial muscle ten- sion, and improved myocardial performance. 2. Clinical implications in a failing heart. Long-standing myocardial disease may shift the Starling curve to the left. Consequently, a significantly elevated PAOP may be re- quired to optimize myocardial performance. It is common for patients who have just undergone heart valve replacement to require a PAOP of 20–25 mm Hg to optimize 20 409 TABLE 20–5 Differential Diagnosis Based on Hemodynamic Parameters* Diagnosis Blood Pressure CVP CO PCWP/LVEDP PAP PVR SVR Cardiogenic shock ⇓ ⇑ ⇓ ⇑ ⇑ ⇑ ⇑ Cardiac tamponade ⇓ ⇑ ⇓ ⇑ ⇑ — ⇑ Hypovolemic shock ⇓ ⇓ ⇓ ⇓ ⇓ ⇑ ⇑ Septic shock ⇓ ⇓ ⇑ ⇓ ⇓ ⇓ ⇓ Pulmonary embolus ⇓ ⇑ ⇓ — or ⇓ ⇑ ⇑ ⇑ *These trends are usually seen with the conditions noted. Clinical variables (medications, secondary conditions) can vary some of these trends. Abbreviations: CVP = central venous pressure; CO = cardiac output; PCWP = pulmonary capillary wedge pressure; PAP = pulmonary artery pressure; PVR = peripheral vascular resistance; SVR = systemic vascular resistance; ⇑ = usually increased; ⇓ = usually decreased; LVEDP = left ventricular end-diastolic pressure, — = usually not changed. 410 Clinician’s Pocket Reference, 9th Edition cardiac output. Patients with a recent MI may require a PAOP of 16–18 mm Hg to opti- mize output. Afterload: Defined as the resistance to ventricular ejection. Measured clinically by the calculation of systemic vascular resistance: (MAP − CVP) × 80 SVR = Cardiac output (L / min) Normal SVR = 900 − 1200 dynes/s/cm3 1. Indications for afterload reduction. • Significant mitral regurgitation • An increased PAOP in the face of an elevated SVR and a decreased cardiac index 2. Treatment. Nitroprusside (Nipride) is the drug of choice. Contractility: The ability of the heart to alter its contractile force and velocity indepen- dent of fiber length is difficult to measure clinically. Digitalis can improve contractility. Care should be maintained to ensure normal levels of serum potassium prior to the adminis- tration of digitalis. Correctable metabolic causes for depressed contractility include: • Hypoxia • Acidosis (pH <7.3) • Hypophosphatemia • Adrenal insufficiency • Hypothermia The most common causes are hypoxia and acidosis. These must be corrected before in- otropic therapy can be effective. DETERMINATIONS OF CARDIAC OUTPUT Several methods are currently available to determine (CO). These include: • Thermal dilution technique • A–VO2 difference calculation Thermal Dilution Technique This requires the use of a PA catheter. A measured amount of saline (usually 10 mL) at a known temperature is injected into the proximal port of the PA catheter, and a temperature- sensitive thermistor located at the distal end of the pulmonary artery senses the temperature change in the surrounding blood. The cardiac output computer then integrates the magnitude and rate of change in temperature and calculates CO. 20 Arteriovenous Oxygen (A–VO2) Difference A reasonable estimate of cardiac output can be made on the basis of A–VO2 difference. A–VO2 difference is a measure between the oxygen content of arterial blood drawn from a peripheral artery and the oxygen content of mixed venous blood drawn from the distal lumen of a PA catheter (Table 20–6). 20 Critical Care 411 TABLE 20–6 Calculation of Cardiac Index Based on A–VO2 Difference A–VO2 Difference Cardiac Index* (Vol %) (L/min/m2) >6 <2 4–5 3–4 <3 >5 *Cardiac index = Cardiac output
Body surface area. A–VO2 difference = Arterial O2 content − Mixed venous O2 content Concept: The A–VO2 difference measures the extraction of oxygen by the tissues during a single transit time through the circulation. Thus, the A–VO2 difference is a function of (1) PaO2, (2) Hgb, (3) CO, and (4) tissue O2 consumption. • If cardiac output is low. Transit time is long and the tissues extract large amounts of oxygen during a single circulation time. Thus, the oxygen content of mixed ve- nous blood is low and the A–VO2 difference is large • If cardiac output is high. Circulation time is shorter and the amount of oxygen ex- tracted is low. Consequently, the A–VO2 difference is low Calculations: The A–VO2 difference is inversely proportional to CO. Therefore, the fol- lowing approximations can be made: 1. Determining Oxygen Content. To calculate the A–VO2 difference, the oxygen content of both arterial and mixed venous blood must determined. Oxygen content describes the amount of O2 the blood is able to carry. Because only a small percentage of O2 is dissolved in plasma, the vast majority is carried by hemoglobin. Hence, Oxygen content = Oxygen bound to Hgb + Oxygen dissolved in plasma Arterial O2 content (CaO2) = (SaO2 × Hgb × 1.39) + (0.0031 × PaO2) where SaO2 is arterial O2 saturation, Hgb is hemoglobin content in g/dL, and PaO2 is arterial partial pressure of O2. The constant 1.39 is the O2-binding capacity of Hgb (mL of O2/g of Hgb), and 0.0031 is mL of O2 dissolved in 100 mL of plasma per mm Hg of PaO2. The nor- mal O2 content of arterial blood is 16–20 mL of O2/100 mL of blood. Similarly, 20 CvO2 = SvO2 × [Hgb] × 1.39 + (0.0031 × PvO2) where CvO2 is the O2 content of mixed venous blood, SvO2 is the mixed venous O2 satura- tion. Assuming that the amount of dissolved blood in plasma is small, then: 412 Clinician’s Pocket Reference, 9th Edition A–VO2 = CaO2 − CvO = 1.39 × Hgb × (SaO2 − SVO2) 2. Calculation of A–VO2 Difference. • Obtain hemoglobin concentration. • Determine SaO2 from heparinized peripheral arterial blood or from a pulse oximeter. • Determine SvO2 from a heparinized mixed venous blood sample from the distal lumen of a PA catheter or from an oximetric SvO2 monitor (see the following discus- sion). • Calculate the A–VO2 difference according to the preceding formula, and determine the CI based on Table 20–6. Continuous SvO2 Monitoring Oximetric pulmonary artery catheters house fiberoptic channels that allow direct measure- ment of mixed venous saturation (SvO2). These fiberoptics carry light impulses that are re- flected by hemoglobin according to its O2 saturation. An optical microprocessor then displays a continuous graph of SvO2 measurements. Calibration is periodically confirmed with a heparinized blood sample drawn from the oximetric catheter’s distal port. Clinical Application • Follow trends in the O2 supply/demand balance. • A decrease in SvO2 is often the first indicator of early organ dysfunction. This early warning allows correction of the problem before hemodynamic compromise. • Treatment interventions (eg, transfusions, fluid mobilization, drugs) may be assessed by following SvO2 changes long before other hemodynamic parameters are adversely affected. • Clinically, SvO2 values between 60% and 80% represent adequate tissue perfusion. • SvO2 of <60% should prompt an immediate assessment of O2 delivery or unrecog- nized conditions causing increased O2 demand. As O2 delivery falls, SvO2 falls be- cause there is less O2 for the tissues to consume. Similarly, if O2 consumption increases, then SvO2 also falls. A decline of SvO2 should therefore prompt a review of the parameters describing O2 delivery (ie, CO, Hgb, SaO2) and consumption (SaO2 − SvO2). These parameters identify the causes of SvO2 decline and their spe- cific treatments: • SaO2 <90% demands increased ventilatory support. • Decreased CO requires optimizing myocardial function. • Low Hgb requires transfusion. • SvO2 of >80% indicates increased metabolic demands, requires evaluation for condi- tions such as unrecognized seizures, shivering, mobilization, and large tissue defects (Figure 20–9). • Inaccurate readings of SvO2 may occur as a result of fibrin buildup on the tip of the catheter, fiberoptic fracture (rare), and impingement of the tip of the catheter on the vessel wall. Overall, however, these catheters are accurate and sensitive with daily 20 calibration. Continuous Cardiac Output This technology allows measurement of the CO on a continuous basis. The specially de- signed PA catheter emits small pulses of energy that heat the surrounding blood. The cardiac 20 Critical Care 413 Mixed Venous O2 Saturation (SvO2) < 60% Requires immediate assessment Check O2 Delivery Check O2 Consumption SaO2 (%) [Hgb] CO ≠ O2/Metabolic needs Evaluate Evaluate for Evaluate Evaluate for unrecognized ventilation unrecognized cardiovascular conditions requiring and blood loss system increased metabolic oxygenation or anemia activity FIGURE 20–9 Algorithm for assessment of decreased SvO2. output computer then calculates the CO based on the magnitude and the rate of temperature change. Continuous SaO2 Monitoring (Pulse Oximeter) The same fiberoptic technology used to measure mixed venous O2 saturation is also used to measure arterial O2 saturation (SaO2). A light-emitting external probe is placed around a well-perfused appendage such as a digit, earlobe, lip, or bridge of the nose. The light is transmitted through the appendage to be reflected by hemoglobin according to its O2 satura- tion (recall that the hemoglobin molecule absorbs different wavelengths of light at different O2 saturations). The oximeter, in addition to calculating Hgb O2 saturation, can also deter- mine the pulse rate and is referred to as the “pulse oximeter.” An SaO2 of <90% implies in- adequate oxygenation and requires immediate intervention. However, an SaO2 >90% does not necessarily imply adequate O2 delivery (see following section). Pulse oximeter is not useful in the setting of smoke inhalation and CO poisoning. SHOCK STATES Shock is defined as inadequate perfusion or oxygen delivery to meet metabolic demand. Types of Shock Shock can be divided into four major classes. Specific therapeutic interventions are also dis- cussed in this chapter on page 431 and in Chapter 21 (page 460). 20 • Hypovolemic (low or high hematocrit) • Cardiogenic • Septic • Neurogenic 414 Clinician’s Pocket Reference, 9th Edition Hypovolemic Shock: Is due to acute loss of extracellular volume. Most often due to hemorrhage in the setting of trauma but may also be due to diarrhea, vomiting, or thermal injury. Characterized by a low cardiac output, low PAOP, and elevated SVR. SvO2 is de- creased. Therapy. Should be directed toward volume replacement and increased hemoglobin concentration to improve myocardial performance. Cardiogenic: May be due to intrinsic pump failure, dysrhythmia, or compression (ie, tamponade). Characterized by a low cardiac output, high PAOP, and elevated SVR. The basic defect is one of myocardial performance. SvO2 is decreased. Therapy. Should be aimed at optimizing PAOP and increasing contractility, while de- creasing SVR. Septic (Systemic Inflammatory Response Syndrome): Sepsis implies that the shock state is due to an infectious cause. The SIRS has similar hemodynamic characteristics but is not due to an infectious agent (ie, sterile pancreatitis). Characterized by a high CO, low PAOP, and low SVR. Septic shock is characterized by prearteriolar shunting, which re- sults in a false increase in SvO2,

despite tissue hypoxia. Therapy. Should be aimed at increasing PAOP and increasing SVR simultaneously. In true septic shock the primary treatment is therapy directed against the infectious cause (ie, drainage of abscess). Neurogenic: Is typically due to high cervical spine injuries or high spinal anesthetics. Characterized by a low cardiac output, low PAOP, and low SVR. SvO2 is decreased. Therapy. Should be aimed at increasing SVR. In the setting of acute trauma with spinal cord injury always assume hemorrhage is the cause of hypotension and treat with fluid resuscitation before using vasoactive agents to raise SVR. Summary Shock describes states of inadequate tissue perfusion and O2 delivery. SvO2 is decreased in all shock states except septic shock. The goal in all shock states is to improve myocardial performance by effecting changes in preload, afterload, contractility, and systemic vascular resistance. The PA catheter is used to guide these cardiovascular manipulations. CLINICAL PULMONARY PHYSIOLOGY The goal of treating any critically ill patient is to optimize both oxygenation and tissue per- fusion. Pulmonary and cardiovascular physiology are intimately interwoven to achieve this goal. It does little good to optimize cardiovascular function if, because of poor pulmonary function, there is no oxygen for the hemoglobin to transport (ie, low SaO2). Ventilation refers to the mechanical movement of air into and out of the respiratory system. Oxygenation refers to the diffusion of oxygen from the alveoli to the blood in the pulmonary capillaries and from there to the tissues. Figure 20–10 shows ventilation and oxygenation in typical alveoli. 20 Ventilation Several parameters, such as volumes and capacities, are important in assessing the adequacy of ventilation. Spirometry provides both dynamic information (patient’s ability to move air into and out of the lungs) as well as static volume measurements. The subdivisions of the lung capacities are shown on a spirometric graph in Figure 20–11. 20 Critical Care 415 Ventilation O2 O2 Oxygenation FIGURE 20–10 Ventilation and oxygenation in typical alveoli. Basic Lung Volumes: Four basic lung volumes that together make up the total lung ca- pacity (See Figure 20–11): 1. Tidal volume. The volume of inspired gas during a normal breath. In healthy individu- als at rest, the tidal volume is 6–10 mL/kg. Inspiratory Reserve Vital Inspiratory Volume Capacity Capacity (IRV) (VC) (IC) Tidal Volume Volume (L) (TV) Expiratory Reserve Volume (ERV) Residual Total Lung Functional Volume Capacity Residual (RV) (TLC) Capacity 20 (FRC) Time FIGURE 20–11 Spirometric graph with volumes and capacities of the lung. 416 Clinician’s Pocket Reference, 9th Edition 2. Inspiratory reserve volume. The volume of gas that can be maximally inspired be- yond the amount inspired during a tidal volume breath 3. Expiratory reserve volume. The volume of gas that can be maximally expired beyond the amount expired at the end of a tidal volume breath 4. Residual volume. The volume of gas that remains in the lung after a maximal expira- tory effort Lung Capacity: The sum of two or more of these lung volumes make up four divisions called lung capacities (See Figure 20–11). 1. Total lung capacity. The total amount of gas in the lung at the end of maximal inspira- tion 2. Vital capacity. The volume of gas expired after a maximal inspiration followed by maximal expiration. Frequently used in determining whether a patient can successfully be weaned from the ventilator. Normal vital capacity is 65–75 mL/kg. A vital capacity of <15 mL/kg is an indication for continued ventilatory support. VC = ERV + TV + IRV (Figure 20–12). 3. Inspiratory capacity. The volume of gas expired from maximal inspiration to end TV. IC = TV + IRV. 4. Functional residual capacity. The gas remaining in the lung following normal expira- tion (tidal volume). Acts as a buffer against extreme changes in alveolar PO2 and conse- quent dramatic changes in arterial PO2 with each breath. FRC = ERV + RV (Fig- ure 20–13). Clinical Implications These volumes and capacities are important parameters for assessing ventilation because they may change under different conditions (ie, atelectasis, obstruction, consolidation, small airway collapse). For example, the ERV decreases with small airway collapse, thus decreas- ing FRC. These alterations in lung volumes consequently affect respiratory reserve and the TLC O2 CCV Collapse of small airways now tends to 20 FRC>CCV RV FRC=CCV FRC<CCV occur at the end of expiration FIGURE 20–12 Functional residual capacity (FRC) and critical closing volume (CCV). TLC = total lung capacity; RV = residual volume. 20 Critical Care 417 TLC CCV FRC<CCV RV Addition FRC>CCV of PEEP FIGURE 20–13 The effect of positive end-expiratory pressure (PEEP) is to increase the functional residual capacity (FRC); CCV = critical closing volume; TLC = total lung capacity; RV = residual volume. patient’s ability to ventilate and oxygenate. The contributing factors and the point at which they influence such volume changes must be understood to optimize support. The critical closing volume is an expression that describes the minimum volume and pressure necessary to keep small airways from collapsing during expiration. Critical Closing Volume: The volume of gas and, consequently, pressure in the lung during expiration at which small airway collapse occurs. When collapse occurs, blood is shunted around nonventilated alveoli, thus decreasing the available surface area for gas ex- change. The critical closing volume is greatly affected by compliance. Therefore, different minimum volumes and pressures may be required to prevent collapse under varying lung conditions. If the CCV is greater than the FRC (air in the lung after tidal expiration), col- lapse tends to occur (see Figure 20–12). One method to overcome the CCV is to increase the amount of positive end-expiratory pressure in the lung (see the following discussion on PEEP). The effect of PEEP is to in- crease FRC by preventing small airway collapse at the end of expiration. This improves alveolar ventilation, decreases shunting and improves oxygenation (see Figure 20–13). Lung compliance. Relates the change in lung volume and the change in pressure re- quired to produce volume change (Figure 20–14). May be measured at the bedside and is a reflection of FRC and CCV. ∆V Compliance = ∆P Dynamic compliance is determined by measuring the tidal volume and dividing it by 20 the peak inspiratory pressure. Tidal volume Dynamic compliance = Peak inspiratory pressure − PEEP 418 Clinician’s Pocket Reference, 9th Edition Normal Less compliant Same pressure produces a smaller volume in the less compliant lung. Increasing positive pressure maintains volume in the less compliant lung. FIGURE 20–14 Concept of pulmonary compliance. Normal > 80–100 mL/cm H2O Static compliance is similarly calculated by substituting static peak pressure for peak inspiratory pressure. Static peak pressure is measured by occluding the exhalation port at the beginning of exhalation (no flow = static pressure). Comparing dynamic with static compliance may indicate the type of processes causing changes in the elasticity of the lung. Dynamic compliance is affected by both elasticity and airway resistance. Static compliance, in contrast, is not affected by airway resistance be- cause there is no flow. Hence, a reduction in dynamic compliance without a change in static compliance indicates an airway resistance problem such as obstruction, bronchospasm, or collapse of the small airways. A reduction in both static and dynamic compliance may indi- cate a decrease in lung elasticity such as pulmonary edema, atelectasis, or excessive PEEP. Oxygenation Oxygenation is the process of transporting oxygen from the alveolus across the capillary membrane into the pulmonary circulation and subsequently distributing that oxygen to the body’s tissues. Tests for the assessment of oxygenation include 20 • Measurement of arterial O2 saturation (SaO2) with pulse oximetry • Calculation of oxygen delivery (or carrying capacity) • Calculation of right-to-left shunt fraction (Qs/Qt) Arterial Oxygen Saturation: See page 162. 20 Critical Care 419 Oxygen Delivery: Delivery of O2 to the tissue, also called the O2 carrying capacity, de- pends on CO in addition to the oxygen content of blood (CaO2). O2 delivery = CO × CaO2 = CO (L/min) × SaO2 × 1.39 [Hgb] × 10 Normal delivery is around 800 mL of O2/min, with an average normal O2 uptake of 250 mL of O2/min. Note that this equation simplifies O2 delivery to three parameters: CO, SaO2, and [Hgb]. These are measured with a PA catheter, pulse oximeter, and spun hematocrit, respectively. Calculating the A–a Gradient: To calculate the alveolar-to-arterial gradient: 1. Place the patient on 100% oxygen (FiO2) for 20 min. 2. Next obtain a peripheral arterial blood gas measurement. 3. Calculate the alveolar PO2. After breathing 100% oxygen for 20 min, the only gases other than oxygen within the alveoli are H2O and excreted CO2 from tissue metabo- lism. Thus, the partial pressure of oxygen within the alveoli is easily calculated. The alveolar PO2 equals 760 Barometric pressure (in torr) −47 Partial pressure H2O −40 PCO2 from peripheral sample 673 Alveolar PO2 (PAO2) 4. Subtract the peripheral arterial oxygen content (PaO2) from the alveolar PO2 Example: 673 Alveolar PO2 (PAO2) −200 Peripheral PaO2 473 A-a gradient Rule: The larger the gradient, the more serious the degree of respiratory compromise. Any A–a gradient >400 torr indicates severe respiratory distress resulting from a process in- terfering with oxygen transfer (low PaO2). (Normal A–a gradient = 20–65 torr) Shunt Fraction: In clinical practice, the A–a gradient is calculated primarily because it may be used to calculate the shunt fraction equation. The shunt fraction (normal = <5%) re- flects the ratio of ventilated alveoli to perfused capillaries. A shunt fraction of 5% (assuming normal perfusion) means that 5% of the blood leaving the pulmonary capillaries has passed without being oxygenated. In an ideal state, the volume of lung ventilation equals the vol- ume of pulmonary capillary blood flow (Figure 20–15). Alterations in these ventilation– perfusion relationships result from two causes: • Relative obstruction of alveolar ventilation • Relative obstruction of pulmonary blood flow 1. Perfusion greater than ventilation: Figure 20–16 depicts the extreme situation in which alveolus A receives no ventilation, but perfusion continues. Therefore, a com- plete pulmonary A–V shunt exists with respect to that alveolus. 2. Ventilation greater than perfusion: Figure 20–17 depicts uniform ventilation to A 20 and B, but no blood flow to the alveolus. This situation increases physiologic dead space and increases the shunt equation. 3. Compensation mechanism: Figure 20–18 represents the compensatory change that occurs when an alveolus is partially occluded. Blood flow is preferentially shunted to other, more efficiently ventilated alveolar units. 420 Clinician’s Pocket Reference, 9th Edition Mixed venous blood Arterial V/Q = 1 blood FIGURE 20–15 Ventilation–perfusion (V/Q) ratio. Principle. It is important to recognize that at any given time, even in the normal state, grada- tions of all these situations exist simultaneously within the lung. The normal shunt fraction is approximately 5%. Alterations in either ventilation or perfusion can seriously affect oxy- genation. 1. Decreased lung-to-blood transfer. Associated factors are • Pulmonary edema • ARDS • Atelectasis • Pneumonia O2 A 20 V/Q < < 1 FIGURE 20–16 Perfusion greater than ventilation. 20 Critical Care 421 A B V/Q > > 1 FIGURE 20–17 Ventilation greater than perfusion. 2. Decreased perfusion. Associated factors are • Massive PE • Continued micropulmonary embolization Calculation of the Shunt Fraction. Q is the mathematical symbol for flow. Therefore, Qs is the symbol for the amount of flow through the pulmonary shunt. Qs is defined as that por- tion of the cardiac output that does not participate in gas exchange, that is, the volume of blood that is shunted past nonventilated alveoli. Qt is the symbol for total cardiac output. Therefore, the volume of blood shunted past nonventilated alveoli divided by the total car- diac output (shunted plus nonshunted blood) is Qs/Qt (Figure 20–19). The shunt fraction is defined as Qs (%) CCO 2 − CaO = 2 × 100 Qt CCO 2 − CvO 2 O2 O2 20 FIGURE 20–18 Compensation for ventilation–perfusion mismatching. 422 Clinician’s Pocket Reference, 9th Edition O2 Qs Qt FIGURE 20–19 Representation of the shunt fraction. where CCO2 is O2 content (mL/100 mL) of blood leaving the alveolar capillary bed, CaO2 is arterial O2 content (mL/100mL), and CvO2 is mixed venous O2 content (mL/100mL) in the pulmonary artery. The oxygen content of the capillary blood (CCO2) is calculated using the alveolar PO2 (PAO2) from the alveolar–arterial gradient calculation. CCO2 = [Hgb] (1.39) (1.0) + PAO2 (0.0031) where CaO2 is measured when the patient should be

on and FiO2 of 1.0 (100% O2). Similarly, the O2 content of mixed venous blood found in the pulmonary artery may be calculated as follows: CVO2 = [Hgb] (1.39) (SvO2) + PVO2 (0.0031) where SvO2 is the O2 saturation of mixed venous blood. Concept of the Shunt Fraction. Qs/Qt represents the amount of pulmonary flow “shunted,” or not participating in gas exchange over the total cardiac output. For example, a shunt fraction of 0.25 indicates that 25% of the pulmonary blood flow is shunted. Thus, the equation serves as a useful index of ventilation–perfusion inequality. The normal value is <5%. Breaking the equation down reveals that the numerator reflects lung-to-blood transfer 20 (ie, A–a gradient), or “ventilation.” The denominator describes O2 consumption (ie, A–VO2 difference), which, in turn, reflects CO, or “perfusion.” Simplifying the denominator further illustrates that this equation is also a function of the four basic measured parameters de- scribing O2 delivery and demand: SaO2, CO, Hgb, and SvO2. Knowledge of these four mea- surements along with the alveolar–arterial gradient allows for early recognition and treatment of ventilation–perfusion mismatching. 20 Critical Care 423 Alveolar-to-Arterial Gradient [P(A–a)O2] Provides an assessment of alveolar–capillary gas exchange • Alveolar PO2 (PAO2) minus calculated • Arterial PO2 (PaO2) minus measured Calculating the A–a Gradient. To calculate the alveolar-to-arterial gradient: 1. Place the patient on 100% oxygen (FiO2) for 20 min. 2. Next obtain a peripheral ABG measurement. 3. Calculate the alveolar PO2. After breathing 100% oxygen for 20 min, the only gases other than oxygen within the alveoli are H2O and excreted CO2 from tissue metabo- lism. PaO [(713) × Fi − (Pa )] − 2 O2 CO2 0.8 INDICATIONS FOR INTUBATION The decision to intubate a patient for prolonged ventilator support is one of the most diffi- cult decisions for clinicians. It is easy for the physician to be lulled into a false sense of se- curity by marginal blood gases. The following indications can be used as a basic checklist for respiratory support: • Inability to adequately ventilate (eg, chest trauma, sedation, paralyzed or fatigued respiratory muscles) • Inability to adequately oxygenate (eg, pulmonary edema, ARDS) • Excessive work of breathing (eg, prophylaxis for impending collapse) • Protection of airway (eg, unconscious, altered mental status, massive resuscitation, facial trauma) These basic indications should be used in conjunction with clinical judgment in the final decision for mechanical ventilation. The decision to intubate, if made in a timely and appro- priate fashion, can turn an otherwise traumatic intubation into a controlled and elective pro- cedure. Table 20–7 lists some common parameters used to evaluate the need for respiratory support in adults. MECHANICAL VENTILATORS Classes of Ventilators The two classic types of ventilator are the pressure-limited and the volume-limited ventila- tors. Although newer ventilators combine many of the qualities of both classes, it is concep- tually advantageous to discuss the two types separately. Additionally, several other types of ventilators are occasionally used. Pressure Limited: These ventilators deliver a volume of air until a preset pressure is reached. They are used in some neonatal units. They are not generally used to ventilate adult patients, because changes in airway pressure and in lung and chest wall compliance may re- sult in an inadequate minute ventilation. This technique is reserved for patients who fail to 20 respond to traditional modes of ventilation. Volume Limited: A preset volume of air is delivered regardless of the opposing pres- sure. This is the most common class of ventilator used. (Note: A pressure limit setting usu- ally allows the venting of excessive pressure to prevent barotrauma.) 424 Clinician’s Pocket Reference, 9th Edition TABLE 20–7 Indicators of Respiratory Failure Normal Range Condition (adults) PaCO2 >60 mm Hg 35–45 mm Hg PaO2 <70 mm Hg on 50% mask 80–100 mm Hg on room air Tachypnea >30 breaths/min 10–20 breaths/min Altered mental status such that the patient is unable to protect the airway against aspiration High-Frequency Ventilation: Rapid oscillations of breath (60–1200 cycles) used with or without the bulk delivery of gases to the lung. Several forms of this type of ventila- tion exist, including high-frequency jet ventilation, high-frequency positive pressure ventila- tion, and high-frequency oscillation. Ventilator Modes Ventilator modes are represented in Figure 20–20. Controlled Ventilation: The patient gets a breath only when it is delivered by the ma- chine. The patient cannot initiate any of his or her own breaths. Used in the past on patients who were intentionally paralyzed by drugs. Assist Controlled: The patient gets a full mechanical tidal volume each time he or she attempts an inspiratory effort. The respiratory frequency is determined by the patient, al- though a backup rate is set to ensure a minimum minute ventilation. • Advantages of AC is that patients can easily increase their minute ventilation even if they are weak and have a poor inspiratory effort. • Disadvantage is the predisposition to hyperventilation if the patient becomes agi- tated or has an altered respiratory drive because of neurologic injury. Agitation may also lead to “breath stacking,” in which the ventilator delivers a second tidal volume before completing the expiratory phase of the first breath. Fortunately, this is rarely a clinical problem because the patient often feels more comfortable and consequently less agitated because of the decreased work of breathing on AC. Synchronous IMV: The respirator delivers a set number of breaths each minute and al- lows the patient to supplement ventilation with his or her own inspiratory efforts between machine breaths. This allows the patient to use the respiratory muscles. As the ventilator 20 rate decreases progressively, the patient assumes more of the work of breathing. The ventila- tor also senses when the patient is taking a breath and will not deliver the mandatory breath until after the patient’s own breath is completed. This was developed to prevent the patient’s working against the ventilator or receiving a double tidal volume (ie, a mechanical tidal vol- ume on top of a spontaneous breath). This is the most commonly used type of ventilatory mode in conjunction with pressure support and PEEP. 20 Critical Care 425 Controlled ventilation (CV) Mechanical ventilation 0 Rate is fixed by ventilator. Patient is not allowed to breathe spontaneously in between mechanical breaths. Assist-controlled ventilation (AC) 0 Each inspiratory attempt triggers a mechanical breath. Synchronous intermittent mandatory ventilation (SIMV) 0 Patient is allowed to breathe spontaneously in between synchronized mechanical breaths. Pressure support ventilation (PSV) + SIMV 0 Patient triggers positive pressure support during inspiration of spontaneous breath - - in between SIMV mechanical breaths. Time FIGURE 20–20 Representation of different ventilator modes. 20 Volume 426 Clinician’s Pocket Reference, 9th Edition Pressure Support Ventilation: A preset level of positive pressure is turned on only during the inspiratory phase and is turned off during expiration. The patient controls the rate and inspiratory time while augmenting tidal volume and inspiratory flow. The higher the pressure support, the less work the patient expends to take a breath. Thus, PSV is comfort- able because the patient has more control of his or her ventilation. PSV serves as an ideal weaning mode because the pressure can be turned down slowly, with changes as small as 1 cm H2O. This allows the patient to assume the workload of breathing in small increments. PSV is often integrated with SIMV as a backup to ensure a minimum minute ventilation. Positive End-Expiratory Pressure: Positive pressure applied during expiration. It represents the supraatmospheric pressure remaining in the airways at the end of expiration. PEEP increases alveolar ventilation by preventing small airway collapse, thereby increasing FRC. PEEP also is often used prophylactically against atelectasis, particularly in the postop- erative period. It has become a standard modality to treat pulmonary edema. Increasing lev- els of PEEP is typically used to decrease the FiO2, in an attempt to limit oxygen toxicity. One disadvantage of PEEP, however, is that it may decrease the cardiac index by decreasing left ventricular end-diastolic volume and should be used cautiously in patients at risk for myocardial ischemia. Pressure Regulated Volume Control: This mode of ventilation is used in the setting of increased airway pressure. A microprocessor in the ventilator adjusts the pressure needed to achieve the proper tidal volume. Continuous Positive Airway Pressure: Positive pressure throughout inspiration and expiration without mechanical assistance during ventilation. This is equivalent to PS plus PEEP at a constant pressure level. The patient does all the breathing on his or her own. Often used as a last step before extubation. A CPAP trial may be performed at room air or an FiO2 of 40%. (See the discussion on extubation-weaning trials page 427.) High-Frequency Ventilation: The physiologic explanation of HFV defies conven- tional teaching and is under current study. Despite the marked reduction in flow rates, oxy- genation and CO2 exchange are still achieved. HFV may be ideally suited to treat such conditions as bronchopleural fistulas or may serve as a more desirable form of ventilation during surgeries requiring a minimum of lung movement. Ventilator Management Ventilator Orders Once the decision has been made to place a patient on a ventilator, the patient must be intu- bated with an appropriate endotracheal tube (see Chapter 13, page 268). The following is a sample of typical initial ventilator orders for an adult: • Mode (ie, AC, SIMV) • FiO2 30–100% • Rate 8–12/min • Tidal volume 5–7 mL/kg 20 • Pressure support (level depends on the clinical situation) • PEEP (5 cm H2O or higher, if needed) Ventilator Setting Changes The following four basic respiratory parameters can be changed to improve ventilation, oxygenation, and compliance, and to prevent ventilator induced lung injury: 20 Critical Care 427 • FiO2 • Minute volume (tidal volume X rate) • Pressure support • PEEP 1. FiO2. Initially, an FiO2 that ensures a saturation (SaO2) >90% is set on the ventilator. Once adequate oxygenation is established, the FiO2 is decreased to avoid oxygen toxic- ity. Because of the danger of oxygen toxicity, an FiO2 >50% is to be avoided. Increasing the level of PEEP is often a helpful means of decreasing the FiO2 requirement while maintaining adequate oxygenation. 2. Minute volume. Adjust to maintain PCO2 within a normal range (35–45 mm Hg). Usu- ally done by increasing tidal volume. Changes in rate are usually limited by a decrease in PCO2, with a resultant respiratory alkalosis. 3. Pressure support. After the patient’s respiratory pattern is established on SIMV, pres- sure support may be added initially at a level of 5–8 cm H2O. Pressure support may then be turned up to a level that allows the patient to breathe at a comfortable rate (eg, <30 bpm). Depending on the stability and mental status of the patient, the number of SIMV backup breaths may be turned down to allow the patient more control of his or her ventilation. PS rarely needs to be turned up beyond 35 cm H2O. 4. PEEP. Added to decrease FiO2 while maintaining PaO2. Five centimeters of PEEP is considered physiologic and is often enough to stabilize the PO2. If the patient continues to deteriorate, PEEP is added in 2- to 3-cm increments until oxygenation is improved. This usually is at a level of 10–12 cm. Serial measurements of compliance are made to confirm improvement in pulmonary mechanics. High-Dose PEEP. If additional PEEP is required, a pulmonary artery catheter is essen- tial to monitor cardiac output, mixed venous saturation, pulmonary artery pressures, and the shunt fraction. Static pulmonary compliance and oxygen saturation are also followed. At high levels of PEEP, intrathoracic pressure increases to a point that venous return is im- paired. Thus, left ventricular end-diastolic volume decreases along with cardiac output. This point defines the maximum level of PEEP and may vary considerably from patient to patient or for the same patient over time. PEEP Side Effects • Falsely elevated PAOP (PCWP) • Decreased cardiac output • Barotrauma (pneumothorax, alveolar rupture, pneumomediastinum) Ventilator Weaning: Prior to the successful weaning of a patient from the ventilator, assess the patient’s pulmonary mechanics and oxygenation. Additionally, the major problem that required the patient be placed on mechanical ventilation must have been corrected. Pulmonary Mechanics. These provide useful information regarding a patient’s ability to perform the work of respiration. Routine pulmonary mechanics consist of: • Vital capacity • Tidal volume • Spontaneous respiratory rate 20 • Lung compliance • Inspiratory force

Inspiratory Force. The maximum negative pressure that can be exerted against a com- pletely closed airway. A function of respiratory muscle strength. An inspiratory force 428 Clinician’s Pocket Reference, 9th Edition between 0 and –25 would indicate that the patient is incapable of generating adequate inspi- ratory effort to allow extubation. Criteria for Weaning. These are based on the assessment of pulmonary mechanics and of oxygenation (Table 20–8). Checklist for Weaning • Correction of primary problem (eg, pneumonia has been treated, hemodynamic stability) • Level of consciousness stable or improving • Stable vital signs • Respiratory rate <30 • Blood gases in the vicinity of: SaO2 >90% PaO2 >70 mm Hg PCO2 <55 mm Hg pH >7.35 • Vital capacity >15 mL/kg • Tidal volume in adults (50–70 kg) >400 mL • Inspiratory force > –30 cm H2O Weaning Modes. Modern respirators are designed to facilitate weaning. Once the pre- ceding criteria have been met, a ventilator mode appropriate to the clinical situation, such as SIMV or PSV, is usually selected. SIMV and PSV are considered weaning modes because the patient is allowed to assume more of the workload of breathing as mechanical support is withdrawn. Extubation Trials. Once weaning has achieved minimal ventilatory settings, various trials off mechanical support (while still intubated) may be attempted. CPAP trials with 5 cm of positive pressure is the most commonly used. For example, a 5-cm CPAP trial with TABLE 20–8 Criteria for Weaning from Mechanical Ventilation Parameter Value Pulmonary mechanics Vital capacity >10–15 mL/kg Resting minute ventilation <10 L/min (tidal volume × rate) Spontaneous respiratory rate <30 breaths/min Lung compliance >100 mL/cm H20 Negative inspiratory forces (NIF) > −25 cm H20 Oxygenation 20 A-a gradient <300–500 mm Hg Shunt fraction <15% PO2 (on 40% FiO2) >70 mm Hg PCO2 <45 mm Hg 20 Critical Care 429 an FiO2 at 21% (room air) or 40% should result in a PaO2 of >50 mm Hg or 70 mm Hg, respectively. T-piece trials, which provide only humidified air with no pressure, are also oc- casionally used, but may be unnecessarily stressful to the patient. CPAP is thought to be more physiologic because positive pressure partially counterbalances the added resistance encountered by breathing through a long, narrow ET tube. These trials may vary in duration from 30 min to several hours and are used primarily as the last test prior to extubation. Pa- tients without COPD are usually capable of going from IMV-4, FiO2 30%, and PEEP of 5 cm H2O to an extubation trial. The ventilator remains at the bedside in case respiratory sup- port needs to be restarted. Order of Weaning. The following steps are taken routinely: 1. Sequentially reduce FiO2 by 10% until an FiO2 of 50% is tolerated. Use pulse oximetry (SaO2) to assist in weaning because it reduces the number of ABGs needed. FiO2 can be decreased as long as SaO2 >90–92% or PaO2 >70 mm Hg. 2. Sequentially reduce the IMV rate to a level of 4 breaths per minute. Add pressure sup- port to maintain adequate minute volume. ABGs as well as capnography are used to monitor for hypercarbia. 3. Sequentially reduce PEEP in 2- to 3-cm H2O increments while maintaining SaO2 >90%, until a level of 5 cm H2O is achieved. Follow FiO2. If a PA catheter is present, mixed venous saturation information will allow for calculation of the shunt equation. Qs/Qt should be kept below 0.25. 4. Sequentially reduce pressure support by 2- to 3-cm H2O increments, maintaining minute volume until a pressure support of 5 cm H2O is met. Monitor respiratory rate, work of breathing, and PCO2. Essential Tips in Ventilator Management • Avoid changing more than one ventilator parameter at a time. • A PO2 <60 or an SaO2 <90% requires a return to previous levels of respiratory support. • A PO2 of 60–70 or an SaO2 of 90% requires a hold at the current level of respiratory support. • A PO2 >70 or an SaO2 ≥92% allows for progression of weaning. Extubation: A patient who is able to maintain a PO2 >70, a PCO2 <45, and a respiratory rate <25 for 1–2 h on a T piece or CPAP trial is ready for extubation. 1. Disconnect the ET tube from the ventilator or T piece. 2. Suction the patient’s endotracheal tube and oral pharynx. 3. Deflate the endotracheal balloon. 4. Have the patient take a deep breath. 5. As the patient expires forcefully, remove the tube and clean any secretions. 6. Apply nasal cannula at 2–4 L/min. 7. Check postextubation blood gases. SPECIFIC PROBLEMS IN CRITICALLY ILL PATIENTS Adult Respiratory Distress Syndrome 20 ARDS, also called “wet lung” or “shock lung,” is respiratory failure associated with acute pulmonary injury manifested by marked respiratory distress and hypoxia. Pulmonary capil- lary membranes become more permeable, resulting in pulmonary edema in the setting of low to normal pulmonary artery pressures. 430 Clinician’s Pocket Reference, 9th Edition Clinical Criteria for the Diagnosis of ARDS • PaO2: FiO2 ratio of < 200 • Recent diffuse bilateral panlobar infiltrates on chest x-ray • Pulmonary wedge pressure (PAOP) <18 • Lack of an alternative clinical explanation for pulmonary findings Etiology The cause of ARDS is multifactorial. There are three primary mechanisms of injury: 1. Increased pulmonary vascular resistance. Neurogenic pulmonary edema is caused by a dramatic increase in pulmonary capillary hydrostatic pressure. This increase forces fluid across the capillary membrane and results in interstitial and then alveolar edema. 2. Permeability edema. Circulating toxic substances within the bloodstream can cause the pulmonary capillary membrane to become leaky and allow extravasation of protein into the interstitial space. This extravasation increases the interstitial hydrostatic pres- sure and eventually results in injury to the alveolar membrane. At this point, fluid and protein migrate into the alveolar space and directly impede oxygen exchange. Several factors have been implicated as mediators to this increased capillary–alveolar perme- ability, including prostaglandins and oxygen radicals. Sepsis is often the primary cause. 3. Injury to the alveolar membrane. Conditions directly toxic to the alveolar membrane include • Smoke inhalation • High doses of oxygen (>60% FiO2) • Aspiration Treatment Primary efforts are directed at treating the underlying condition while providing sufficient pulmonary support. Currently, no specific therapy is available for ARDS. 1. Aggressive ventilatory support. Use PEEP to maintain the FiO2 <0.6 while maintain- ing a PO2 >70 mm Hg. Use the PaO2, volume status, and level of PEEP to guide ventila- tory management. Although some may advocate increased levels of PEEP to minimize intrapulmonary shunting (Qs/Qt) without regard to PaO2, doing so may necessitate in- creased intravascular volume and inotropic support of the heart. Many clinicians rec- ommend using PaO2 as a guide to increasing PEEP, rather than following the shunt fraction specifically. 2. Aggressive fluid administration. Maintain cardiac output and peripheral perfusion. The use of colloid versus crystalloid remains controversial. Many clinicians recom- mend the use of crystalloid (NS, lactated Ringer’s) and blood to maintain the hemato- crit above 30–35%. 3. Aggressive monitoring. Use a PA catheter to guide fluid administration (by following filling pressures), and observe the effect of added PEEP on cardiac output. Inotropic 20 agents may be indicated if cardiac output remains low despite adequate filling pres- sures. Use an arterial line to obtain arterial blood for frequent ABG determinations. 4. Pulmonary toilet. To manage secretions 5. Chest x-rays. To monitor lung status 6. Watch for associated DIC (see page 434). 7. Steroids are not indicated in the treatment of ARDS. 20 Critical Care 431 Clinical Correlations ARDS should be anticipated in the following clinical situations: • Severe head injury • Severe trauma with prolonged hypotension • Massive fluid resuscitation • Sepsis • Necrotizing pancreatitis • Burn of the respiratory tract or aspiration • Severe chest contusion Shock (See also Algorithm, Chapter 21, page 460.) Shock is inadequate tissue perfusion, and is a syndrome with several possible causes. All four of these have in common a resultant poor perfusion of tissues that leads to tissue in- jury and death if untreated. The most common classification is based on etiology and in- cludes hypovolemic, cardiogenic, septic, and neurogenic types. Treatment of shock is always directed at treatment of the underlying problem, maximizing cardiac performance to restore tissue perfusion, and maintaining essential physiologic support to keep oxygenation and renal function as normal as possible. Hypovolemic Shock: Caused by inadequate circulating blood volume Physiology. Low cardiac output, low wedge pressure, elevated peripheral vascular resis- tance as a result of reflex vasoconstriction Therapy 1. Correct source of blood loss (hemorrhage). 2. Replete intravascular volume with packed cells, isotonic crystalloid fluids (normal saline, lactated Ringer’s), or colloid. Cardiogenic Shock: Caused by primary “pump” failure Physiology. Low cardiac output, high wedge pressure resulting from fluid accumulation in the pulmonary capillary bed, elevated peripheral vascular resistance Therapy. Directed at improving cardiac performance 1. Optimize filling pressures (preload). 2. Decrease afterload (vasodilation with nitroglycerin, nitroprusside, etc). 3. Improve contractility (dobutamine). Septic Shock: Decreased peripheral (systemic) resistance as a result of massive infection Physiology. High cardiac output (until late stages), low wedge pressure, low peripheral vascular resistance Therapy 1. Treat the cause of sepsis (parenteral antibiotics, drainage of abscess). 2. Administer fluids to increase filling pressures. 3. Increase vascular resistance (pressors such as dopamine). 4. Provide inotropic support of the heart as needed. 20 Neurogenic Shock: Caused by loss of sympathetic vascular tone (eg, cord injury) Physiology. Low cardiac output, low wedge pressure, low peripheral vascular resistance Therapy. Optimize filling pressures, increase peripheral vascular resistance (norepi- nephrine, phenylephrine). 432 Clinician’s Pocket Reference, 9th Edition Acute Renal Failure Many patients in the ICU are unable to receive oral nutrition or fluid. Therefore, particular attention must be paid to fluid and electrolyte requirements in the critically ill patient. The following data provide useful information: • Urine output. One of the best and simplest parameters for following fluid balance. • Daily weight. Because daily changes in weight are mostly the result of loss or gain of fluid. • Pulmonary artery catheter data. In a critically ill patient in whom the fluid status is not discernible, a PA catheter can be placed to determine intravascular fluid status. Oliguria and Progressive Azotemia: These conditions are the final result of a num- ber of pathologic processes that constitute acute renal failure. Once recognized, the pri- mary goal of the clinician is to identify the cause and treat the underlying condition. To simplify the multitude of causes, renal failure is usually divided into prerenal, renal, and postrenal causes. These are outlined in Chapter 6. Acute tubular necrosis. (eg. Nephrotoxic medications, ischemia), intravascular volume depletion, and congestive heart failure are the most common causes of renal failure in the ICU patient. The following outline describes the general approach to the problem of oliguria or anuria in an ICU patient. Physical Examination 1. Vital signs. Hypotension with or without associated tachycardia can be a sign of hypo- volemia, indicating prerenal causes of oliguria. Orthostatic blood changes also point to hypovolemia. 2. Mucous membranes. Dry mucous membranes indicate overall fluid depletion. 3. Lungs. Fluid overload often manifests itself as pulmonary edema, often heard when auscultating the chest. 4. Abdomen. Low urine output may result from postrenal obstruction, which may be manifest as bladder distention, palpable on examination. Bladder palpation may cause pain, also indicating distention. A distended abdomen may indicate ileus with associ- ated fluid sequestration in the bowel. 5. Extremities. Fluid overload may be evident as peripheral edema. Diagnostic Studies 1. Laboratory results 2. Bladder catheterization. If a catheter is in place, irrigate it gently to confirm proper drainage. 3. Radiographic. Renal ultrasonography helps evaluate for possible postrenal obstruc- tion. Avoid intravenous contrast studies if possible. Therapeutic trials. These can be used as an adjunct to differentiate prerenal from renal azotemia. After obstruction has been ruled out, failure to respond to these measures with in- creased urine flow most likely indicates an intrinsic renal cause of azotemia. Furosemide 20 has little effect in ATN. • Fluid challenge (1000 mL of NS infusion, rapid) • Furosemide 80 mg IV push • Mannitol 25 g IV • Dopamine infusion 20 Critical Care 433 Management. As a general approach, daily intake and output should be closely re- viewed, and daily weights are very useful. Follow electrolytes, particularly potassium, closely. Many clinicians remove potassium from the

IV fluids immediately in cases of renal failure to prevent accumulation of deadly potassium levels. Prerenal 1. Optimize hemodynamic status to maximize cardiac output and, hence, renal perfusion. 2. Replete fluids. Use blood in anemic patients; otherwise, use isotonic fluid or albumin. 3. Once you are sure that fluid status is optimal and urine output is still suboptimal, use low-dose dopamine (2–5 mg/kg/min) to dilate the renal vessels. A PA catheter is usu- ally needed to monitor the patient at this point. Renal 1. Optimize fluid status, keeping cardiac filling pressures in the normal range. 2. Try furosemide (20–40 µg) once fluid status is optimal. 3. If there is no response to furosemide, try mannitol 12.5–25 g IV. 4. Metolazone can be given if there is still no response (5–10 mg PO). 5. If the patient is fluid-overloaded, use furosemide in increasing doses to diurese fluid. 6. Restrict fluids, salt, and particularly potassium. 7. Treat the usual metabolic acidosis with sodium bicarbonate. 8. Dialysis may be necessary. Postrenal 1. Check the Foley catheter for patency, replacing it immediately if there is any question. 2. Obtain a urologic consultation. Prostatic obstruction in men can be easily corrected with a Foley catheter. Decompression of the upper urinary tracts may require stents or percutaneous drainage. Stress Ulceration The development of stress ulceration in the ICU patient is a serious complication. Most im- portantly, it is a largely preventable problem. It is common in neurosurgical (Cushing’s ul- cers) and burn (Curling’s ulcers) patients. The pathophysiology is related to diminished blood flow to the viscera in stress situations, leading to alterations in the mucosal barrier to the effects of gastric acid. Prophylaxis • Routine cardiovascular support of perfusion • Routine use of H2 blockers (Pepcid, etc) • Antacid administration (eg, Maalox 30 mL per NG tube q2h). In patients with renal failure, use aluminum hydroxide, avoid magnesium-containing antacids • Enteral feedings, when tolerated, remain a good method to neutralize gastric acid. Treatment of Ulceration 20 1. Early endoscopy is indicated in upper GI bleeding. 2. A clearly visible lesion (bleeding vessel) warrants operative intervention, but diffuse gastritis is best treated initially with aggressive antacid and H2 blocker therapy. Persis- tent bleeding from gastritis may warrant total gastrectomy. 434 Clinician’s Pocket Reference, 9th Edition Acalculous Cholecystitis Cholecystitis in the absence of stones is not uncommon in the ICU patient, and is probably related to diminished blood flow in the critically ill patient, although the exact pathophysiol- ogy remains unclear. First and foremost in the treatment of this potentially fatal condition is to remain vigilant for its development in the critically ill patient. Presenting signs are similar to those in healthy patients with cholecystitis and include right upper quadrant pain, fever, leukocytosis, and elevated liver chemistries (especially bilirubin or alkaline phosphatase). The most valuable test is an HIDA scan. Nonvisualization of the gallbladder is clear evi- dence of cholecystitis. Treatment is surgical (cholecystectomy), and should be done as early as possible to avoid perforation. Nutrition The nutritional needs of the critically ill patient are of major significance in overall patient care. Restoring the patient to an anabolic state will hasten recovery. The details of TPN, or hyperalimentation, as well as enteral feedings are covered in Chapters 11 and 12. Remem- ber the following two rules: 1. The “5-day” rule applies to most patients. If you do not think the critically ill patient can take nutrition for 5 days because of postoperative ileus, intubation, etc, be sure to start nutritional support by the fifth day. 2. “If the gut works, use it.” That is, do not use parenteral nutrition if the GI tract is func- tioning. Enteral nutrition (eg, oral, NG tube, jejunostomy tube) should be used in all patients with a functioning intestinal tract. The enteral feeding is reviewed in Chap- ter 11. Disseminated Intravascular Coagulation DIC is a complex management problem that often presents in the critically ill patient. This clinical syndrome may accompany a number of disease states, including shock syndromes, sepsis, malignancy, and some obstetric conditions. As with many of the pathologic condi- tions that accompany major illness (eg, ARDS), the successful treatment of DIC depends on treating the underlying condition. Diagnosis: The diagnosis of DIC is usually contemplated in the critically ill patient who develops thrombocytopenia, and occasionally an elevated PT. The following list details other laboratory findings that are caused by the effect of plasmin on fibrinogen. They result in increased levels of fibrin monomers and feedback stimulation of the fibrinolytic system, yielding fibrin degradation products and increased plasmin formation. • Low fibrinogen level • Elevated FSP level • Elevated PTT • Microangiopathic RBC morphology Treatment: The treatment of this disease is controversial. 20 1. The most important element of therapy is to identify and treat the underlying cause. 2. Treat associated shock appropriately to maintain cardiovascular stability. 3. If there is evidence of thrombosis (eg, PE), begin heparin therapy with a loading dose of 100 U/kg followed by a drip at 10–15 U/kg/h (see Chapter 22). 4. Administer FFP to replenish fibrinogen. 20 Critical Care 435 5. If the patient is bleeding severely, despite replacement therapy with FFP and platelets, begin antifibrinolytic therapy with epsilon–aminocaproic acid (Amicar). Use a loading dose of 4 g, followed by 1 g/h, for a total of 12 g. In general, if there is no improvement after 12 h, therapy should be stopped. Line Sepsis Indwelling catheters not only provide a convenient means of infusing fluids and medica- tions, but also act as a portal of entry for bacteria. With the widespread use of indwelling intravenous catheters (eg, central venous lines), the diagnosis of infection from the cath- eter itself must be considered when evaluating a febrile patient in the ICU. As a general rule, fever in a person with a central line should be attributed to the line until proven other- wise. The most common mechanism of line sepsis is entry of skin flora along the catheter tract. The use of clear polyurethane dressings left in place for prolonged periods has been associated with increased risk of infection and should be avoided. Some institutions have a policy of routine line changes, over a guidewire, every 3–4 d. Little objective data support this practice; in fact, some evidence suggests that this practice is associated with an in- creased rate of complications. Prevention of line sepsis is best accomplished by meticulous aseptic technique during placement and meticulous care of the line once in place. Treatment: A presumed episode of line sepsis is treated by determining whether the line is actually responsible. Erythema at the entry site may suggest the cause. Short-term cen- tral venous catheters that may be infected are best treated by removing the line. The catheter may be changed over a guidewire, but some centers do not advocate this practice. Cultures of the intracutaneous segment are essential. In the absence of florid sepsis, or if placement of a new line would jeopardize the ability to obtain vascular access, then quantitative cultures of blood from a peripheral site and the line may be obtained and treatment may be based on the results of these cultures, once avail- able. Empiric antimicrobial therapy may be started in the interim. Using isolator tubes (Dupont), colony counts are performed 16–18 h after obtaining the culture. If the colony count from the catheter is equal to or greater than five times the count from the peripheral culture, the result is interpreted as probable catheter infection. Pulmonary Embolism PE is a major cause of death in the United States (approximately 150,000 deaths annually) and the world. Deep venous thrombosis is known to be responsible for a majority of PE in hospitalized patients. It is estimated that about 90% of all PE originate in the femoral–iliac–pelvic veins. DVT is caused by the classical causes of thromboses: vessel in- jury, hypercoagulability, or stasis. Prevention of DVT: Prevention is especially important in “high-risk” patients (those with malignancy, obesity, previous history, age >40 years, extensive abdominal/pelvic surgery, immobilization). For patients undergoing surgery, prevention should be initiated in the operating room. Intermittent compression stockings and the selected use of heparin have 20 greatly reduced the incidence of DVT in the postoperative patient. Remember that prophy- laxis against DVT is effective only when started preoperatively for those patients under- going surgery. Physical Methods. These include leg elevation, intermittent compression devices, early postoperative ambulation. 436 Clinician’s Pocket Reference, 9th Edition Pharmacologic Methods • Heparin 5000 U SQ q12h. Check the platelet count (eg, every 3 days) because of risk of thrombocytopenia. • Coumadin for chronic therapy • Enoxaparin is now the drug of choice in many institutions for high-risk patients, de- spite the high cost of therapy. Diagnosis of Pulmonary Embolus • Maintain a high index of suspicion. • Signs and symptoms. None is diagnostic, but may include dyspnea, tachypnea, tachycardia, chest pain (usually pleuritic), PO2 <80 (compare with baseline). • Routine chest x-ray may show localized volume loss or Hampton’s hump due to pulmonary infarction. • Nuclear V/Q scan. A normal scan effectively rules out PE, and a positive scan is sufficient evidence to treat the patient. An indeterminate scan in a symptomatic pa- tient with a high index of suspicion necessitates angiography. • Spiral CT scan. This scan is helpful in identifying proximal pulmonary emboli. • Pulmonary angiogram. The “gold standard.” Treatment 1. Support oxygenation. Monitor ABGs, and support as indicated. Intubation may be necessary. 2. Use intravenous heparin. Prevents clot propagation, decreases inflammation, and al- lows intrinsic fibrinolysis to lyse the clot. a. Bolus with 80–100 U/kg and start an intravenous drip at 10–15 U/kg/h. Adjust the drip to keep the PTT at 2–2.5 × control values. The half-life of heparin is 1.5 h, so check the PTT at 3–6 h after adjusting the rate of heparin administration. b. Monitor the platelet count because some patients can manifest “heparin-induced thrombocytopenia.” c. Start oral warfarin (Coumadin) by day 7 of heparin therapy, to maintain a thera- peutic ratio. (See Chapter 22, page 637. d. In cases of massive embolus, thrombolytic therapy (streptokinase) can be used in the absence of contraindications. e. Open embolectomy, using cardiopulmonary bypass, has been effective in some cases of massive PE. 3. In patients who cannot undergo systemic anticoagulation (those with recent surgery, stroke, GI bleeding, etc) or patients with recurrent emboli despite adequate therapy, vena caval interruption may be indicated using an intracaval filter or a caval clip (placed transabdominally). QUICK REFERENCE TO CRITICAL CARE/ICU FORMULAS See Table 20–9 GUIDELINES FOR ADULT CRITICAL CARE DRUG INFUSIONS 20 See Table 20–10 20 437 TABLE 20–9 Quick Reference to Common ICU Equations Determination Derivation Normal RAP, CVP Measured 2–10 mm Hg RVP Measured 15–30/0–5 mm Hg PAS/PAD Measured 15–30/8–15 mm Hg PCWP Measured 5–11 mm Hg CO Measured (CO = SV × HR) 3.5–5.5 L/min CI CO × BSA 2.8–4.2 L/min/m2 MAP DBP × (SBP − DBP) 85–90 mm Hg 3 MPAP PAD × (PAS − PAD) 11–18 mm Hg 3 SVR (MAP − CVP) × 80 770–1500 dynes/s/cm5 CO PVR (MPAP − PCWP) × 80 20–120 dynes/s/cm5 CO A–a gradient [(713) x FiO2 − (PaCO2)] − PaO2 Room air 2–22 mmHg 0.8 100% FiO2 10–60 mmHg CaO2 (arterial O2 content) (Hgb x 1.39) SaO2 + (PaO2 × 0.0031) 16–22 mL 02/dL blood CvO2 (mixed venous O2 content) (Hgb x 1.39) SvO2 + (PvO2 × 0.0031) 12–17 mL 02/dL blood C(a-v)O2 (A-VO2 difference) CaO2 − CvO2 = (Hgb × 1.39) (SaO2 − SvO2) 3.5–5.5 mL 02/dL blood O2 carrying capacity Hgb x SaO2 × CO × 10 700–1400 mL/min delivery (continued ) 20 438 TABLE 20–9 (Continued) Determination Derivation Normal O2 consumption (CaO2 − CvO2) × CO x 10 180–280 mL/min Qs/Qt (shunt fraction) (CcO2 − CvO2) × CO x 10 0.05 (CcO2 − CvO2) ICP Measured 0–20 mmHg CPP MAP − ICP keep >70 mmHg Abbreviations: RAP = right atrial pressures; CVP = central venous pressure; RVP = right ventricular pressure; PAS = pulmonary artery systolic; PAD = pulmonary artery diastolic; PCWP = pulmonary capillary wedge pressure; CO = cardiac output; CI = cadiac input; MAP = mean arterial pressure; MPAP = mean pul- monary artery pressure; SVR = systemic vascular resistance; PVR = pulmonary vascular resistance; ICP = intracranial pressure; CPP = cerebral perfusion pres- sure; BSA = body surface

area; DBP = diastolic blood pressure; SBP = systolic blood pressure; FiO2 = inhaled O2; Hgb = hemoglobin; SaO2 = arterial oxygen, SvO2 = mixed venous oxygen saturation; Qs = volume of shunted blood (ie, blood shunted past nonventilated alveoli, not participating in gas exchange); Qt = total cardiac output; CCO2 = O2 content of alveolar-capillary blood; CVO2 = mixed venous O2 content of pulmonary artery blood. 20 439 TABLE 20–10 Guidelines for Adult Critical Care Drug Infusions* (Final Concentration) Drug Dilution Flow Rate = mL/h Usual Dose Range Amrinone 500 mg (2 mg/mL) (Inocor) 250 mL 1500 µg/min = 45 LD = 0.75 µg/kg 1000 µg/min = 30 MD = 5–20 µg/kg/min (150 mL PSS+ 750 µg/min = 22.5 100 mL drug) 500 µg/min = 15 PSS only 350 µg/min = 10.5 Diltiazem (Cardizem) 125 mg (1 mg/mL) Bolus = 0.25 mg/kg 125 mL 5 mg/h = 5 over 2 min; may give 10 mg/h = 10 second bolus 0.35 mg/kg 15 min after initial bolus (100 mL diluent 15 mg/h = 15 +25 mL drug) MD = 5–15 mg/h D5W or PSS Dobutamine 500 mg (2000 µg/mL) 2.5–20 µg/kg/min (Dobutrex) 250 mL 1500 µg/min = 45 (continued ) 20 440 TABLE 20–10 Continued (Final Concentration) Drug Dilution Flow Rate = mL/h Usual Dose Range Dobutamine 1250 µg/min = 37.5 (continued) D5W or PSS 1000 µg/min = 30 750 µg/min = 22.5 500 µg/min = 15 250 µg/min = 7.5 Dopamine 400 mg (1600 µg/mL) 0.5–2.0 µg/kg/min (renal) 250 mL 1400 µg/min = 52.5 2.0–10 µg/kg/min (inotropic) 1200 µg/min = 45 10–20 µg/kg/min (vasopressor) D5W or PSS 1000 µg/min = 37.5 800 µg/min = 30 600 µg/min = 22.5 400 µg/min = 15 200 µg/min = 7.5 Epinephrine 3 mg (12 µg/mL) Initially 1 µg/min 250 mL 4 µg/min = 20 3 µg/min = 15 Titrate to response D5W or PSS 2 µg/min = 10 1 µg/min = 5 Esmolol 5000 mg (10 mg/mL) LD = 500 µ/kg/min over 1 minute (Brevibloc) 500 mL 5000 µg/min = 30 MD = 50 µ/kg/min, titrate to 4000 µg/min = 24 response. D5W or PSS 3000 µg/min = 18 Increase by 50 µ/kg/min increments every 5 minutes (continued ) 20 441 TABLE 20–10 (Continued) (Final Concentration) Drug Dilution Flow Rate = mL/h Usual Dose Range Isoproterenol 2 mg (8 µg/mL) Initially: 1–4 µg/min (Isuprel) 500 mL 10 µg/min = 75 6 µg/min = 45 Titrate up to 20 µg/min D5W or PSS 4 µg/min = 30 2 µg/min = 15 1 µg/min = 7.5 Labetalol 200 mg (1 mg/mL) Bolus = 20 mg over 2 min (Trandate) 200 mL Additional 20–80 mg may be given (160 mL diluent every 10 min until response or +40 mL drug) 2 mg/min = 120 maximum of 300 mg or Initially 2 mg/min D5W or PSS Titrate to response Lidocaine 2 g (8 mg/mL) LD = 1–1.5 mg/kg over 2 min (Xylocaine) 250 mL 4 mg/min = 30 MD = 1–4 mg/min 3 mg/min = 22.5 Maximum 4 mg/min D5W or PSS 2 mg/min = 15 1 mg/min = 7.5 Nicardipine 25 mg (0.1 mg/mL) Initially: 5 mg/h (Cardene) 250 mL 5 mg/h = 50 Titrate to BP: increase rate by 2.5 mg/h 7.5 mg/h = 75 every 5–15 min (continued ) 20 442 TABLE 20–10 (Continued) (Final Concentration) Drug Dilution Flow Rate = mL/h Usual Dose Range Nicardipine D5W or PSS 10 mg/h = 100 Maximum: 15 mg/h (continued) 12.5 mg/h = 125 MD 3 mg/h 15 mg/h = 150 Nitroglycerin 100 mg (400 µg/mL) Initially 5–10 µg/min (Tridil) 250 mL 80 µg/min = 12 Titrate up by 10–20 µg/min every 5 min D5W or PSS 60 µg/min = 9 based on current dose and patient (glass bottle) 40 µg/min = 6 condition 20 µg/min = 3 10 µg/min = 1.5 Nitroprusside 100 mg (400 µg/mL) Initially: 0.3–0.5 µg/kg/min (Nipride) 250 mL 300 µg/min = 45 200 µg/min = 30 Titrate to response every few minutes D5W 150 µg/min = 22.5 Maximum: 10 µg/kg/min 100 µg/min = 15 70 µg/min = 10.5 50 µg/min = 7.5 Norepinephrine 4 mg (16 µg/mL) Initially: 8–12 µg/min (Levophed) 250 mL 12 µg/min = 45 8 µg/min = 30 Titrate to response D5W or PSS 6 µg/min = 22.5 4 µg/min = 15 2 µg/min = 7.5 (continued ) 20 443 TABLE 20–10 (Continued) (Final Concentration) Drug Dilution Flow Rate = mL/h Usual Dose Range Phenylephrine 50 mg (200 µg/mL) Initially: 10–50 µg/min (Neo-Synephrine) 250 mL 100 µg/min = 30 80 µg/min = 24 D5W or PSS 60 µg/min = 18 Titrate to response 50 µg/min = 15 Procainamide 2 g (8 mg/mL) LD = 17 mg/kg over 1 h, or 100 mg (Procan) 250 mL 4 mg/min = 30 every 5 min up to 1 g 3 mg/min = 22.5 MD = 1–4 mg/min D5W or PSS 2 mg/min = 15 1 mg/min = 7.5 Vasopressin 100 units (0.4 units/mL) 0.1–0.4 units/min (Pitressin) 250 mL 0.4 units/min = 60 0.3 units/min = 45 Maximum 0.9 units/min D5W or PSS 0.2 units/min = 30 0.1 units/min = 15 Abbreviation: LD = loading dose; MD = maintenance dose; BP = blood pressure; PSS = physiologic saline solution; D5W = dextrose 5% in water *These agents must be administered in the appropriately monitored clinical setting. Source: Reprinted, with permission, from Thomas Jefferson University Pharmacy and Therapeutic Committee, Philadelphia, PA. This page intentionally left blank. 21 EMERGENCIES Cardiopulmonary Resuscitation Electrical Defibrillation Advanced Cardiac Life Support and Cardioversion and Emergency Cardiac Care* Other Common Emergencies Advanced Cardiac Life Support Drugs CARDIOPULMONARY RESUSCITATION Emergency cardiac care guidelines from the American Heart Association now recommend that health care providers have the following items readily available: gloves, a barrier device or bag mask, and an automated defibrillator to handle cardiac emergencies. In cardiopul- monary resuscitation, remember there are now two sets of ABCDs: Primary Survey • Airway: Assess and manage noninvasively. • Breathing: Use positive pressure ventilations. • Circulation: Perform chest compressions as needed. • Defibrillation: Assess for VT/VF and defibrillate using an AED. These are also called PADs and are becoming widely available in public areas such as airports, sta- diums, health clubs, and shopping malls. Secondary Survey: Uses advanced medical techniques • Airway: Assess and manage with airway device (eg, endotracheal intubation, etc). • Breathing: Verify tube function and placement, use positive pressure ventilation sys- tem through tube. • Circulation: Start IV, attach ECG, use rhythm-based ACLS medications. • Differential Diagnosis: Search for, find, and treat problems according to AHA algo- rithms presented in this chapter. Adult CPR (Victim’s age ≥8 y) One Rescuer 1. Determine unresponsiveness (shake and shout). If the patient is unresponsive, call for help (activate EMS system, eg, call “code,” dial 911). In trauma situation do not move * The section on basis CPR and ACLS are based on guidelines from the American Heart Association and 21 the International Liaison Committee on Resuscitation [Circulation 2000;102 (Sup 1)] and the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care by the American Heart Assocation in Collaboration with the International Liaison Committee on Resuscitation (ILCOR). 445 Copyright 2002 The McGraw-Hill Companies, Inc. Click Here for Terms of Use 446 Clinician’s Pocket Reference, 9th Edition the victim unless in immediate danger. Roll victim on to back as a unit if lying face down. Protect the neck. 2. Kneel at the level of the victim’s shoulder. Open the airway (head-tilt, chin-lift,), deter- mine breathlessness (“look [chest movement], listen [for air escaping], feel [for air movement]”) for no more than 10 s. In the unresponsive victim with spontaneous respi- ration, place the victim in the recovery position. Jaw thrust maneuver recommended as alternative for health care providers especially if neck injury is suspected. If the victim is breathing, place in the RECOVERY POSITION (see page 449). 3. If not breathing, give patient two slow ventilations (2 s/inspiration) while maintaining airway. Use pocket mask or bag mask. Volume should be between 0.8–1.2 L. A barrier device (face shield or mask with one-way valve) is recommended if mouth-to-mouth or mouth-to-nose contact is necessary. Ventilate 10–12 breaths/min. If unable to ventilate, reposition head and try again. If unsuccessful, perform the FOREIGN BODY OB- STRUCTION AIRWAY SEQUENCE (see page 448). 4. Check for circulation (breathing, coughing, movement). Palpate the carotid artery no more than 10 s to determine lack of a pulse. If pulse is present, perform rescue breath- ing: 1 ventilation every 5 s (10–12 ventilation/min). 5. If no pulse, use four cycles of 15 compressions and two ventilations (compression rate 100/min, two ventilations 1.5–2 s each). Depth of compression 1.5–2 in. or slightly greater to generate carotid pulse. Apply compressions to lower half of sternum using the heels of both hands placed on top of each other. 6. After the four cycles (approximately 1 min of CPR), pause and check for return pulse and spontaneous respirations. 7. If no pulse or respiration, resume cycles with two ventilations, then compressions, as noted earlier. 8. Incorporate appropriate ACLS management guidelines. Two-Rescuer Adult CPR For laypersons 1. Second rescuer identifies him or herself. Verify that EMS has been notified. If so, sec- ond rescuer gets into position opposite first rescuer. If EMS not notified, the second rescuer does so before assisting first rescuer. 2. First rescuer continues CPR. 3. If and when first rescuer tires, second rescuer takes over one-person CPR as described in the preceding section. For health care professionals 1. Sequence to continue from one-rescuer CPR as mentioned in previous section. Second rescuer identifies him or herself and gets into position for compressions. 2. First rescuer completes compression and ventilation cycle (15 compression and two ventilations). 3. First rescuer then checks for spontaneous pulse and breathing, states: “No pulse.con- tinue CPR,” then ventilate once (1.5–2 s). 4. Second rescuer resumes compressions at same rate of 80–100/min.(“1 & 2 & 3 & 4 & 5 & pause,” ventilate) Ratio of five compressions to one breath. If airway is protected, do not pause for ventilations. 5. When ready to switch, rescuer doing compressions says “switch & 2 & 3 & 4 & 5 &.” 21 6. Both rescuers change position simultaneously immediately after ventilation. 7. Rescuer who will perform ventilations opens airway and performs a 5-s pulse check. 8. If no pulse, give ventilation. Rescuer states “No pulse.continue CPR.” 21 Emergencies 447 9. In patient with unprotected airway, cricoid pressure may be applied (Sellick’s maneu- ver) by a third rescuer (if health care professional) to help limit gastric distention. Child CPR (Victim’s age 1–8 y) 1. Determine unresponsiveness, and shout for help. Activate EMS system (call code or 911). 2. Open airway (head-tilt, chin-lift; jaw thrust if neck trauma is suspected), determine breathlessness (follow “look, listen, feel” rubric as for adult). If victim is breathing, place in RECOVERY POSITION (see page 449). 3. If victim not breathing, give two ventilations (1–1.5 s). If unable to ventilate, perform the FOREIGN BODY OBSTRUCTED AIRWAY SEQUENCE (see page 448). 4. Check for circulation (breathing, coughing, movement). Palpate the carotid artery for no more than 10 s to determine presence of a pulse. If pulse is present, perform rescue breathing using pocket mask or bag-mask device (20 breaths/min). 5. If no pulse, or if pulse is <60 bpm and perfusion is poor, begin cardiac compressions at five compressions to one ventilation at rate of 100/min. Depth of compressions less than for an adult (1–1.5 in. or one third to one half the depth of chest).Use the heel of one hand at the lower half of the sternum. Pause compressions for ventilations until pa- tient is intubated. 6. Check for return of pulse and spontaneous breathing after 20 cycles (approximately 1 min). 7. Resume cycles with one ventilation (1–1.5 s each), then resume compressions. Infant CPR (Victim’s age, ≤1 y) 1. Determine unresponsiveness, and shout for help. Activate EMS system (call code or 911). 2. Open airway (head-tilt, chin-lift). Do not hyperextend head; however, create adequate head-tilt to accomplish chest rise with breath. If neck trauma suspected, use jaw thrust. If victim is breathing, place in the RECOVERY POSITION (see page 449). 3. If patient is not breathing, give two ventilations (1–1.5 s) using pocket mask or bag- mask device. If unable to ventilate, perform the FOREIGN BODY OBSTRUCTED AIRWAY SEQUENCE using back

blows and chest thrusts as noted on page 448. 4. Check for circulation (breathing, coughing, movement). Palpate the femoral or brachial artery for no more than 10 s to determine presence of a pulse. If pulse is present, con- tinue rescue breathing (20 breaths/min). 5. If no pulse or if pulse is <60 bpm and perfusion is poor, begin cardiac compressions. Draw an imaginary line between the nipples and identify where this line crosses the sternum (intermammary line). The site of compression is one finger breadth below this intersection. Use a compression depth of ¹₂–1 in., using the middle and ring fingers. Use five compressions to one ventilation (rate of compression is 100/min or 120 min for newborns). 6. Use the mnemonic: (“1 & 2 & 3 & 4 & 5 & pause, head-tilt, chin-lift, ventilate− continue compressions”). When patient is intubated, no need to pause. 7. Check for return of pulse and spontaneous breathing after 20 cycles (1 min). Neonatal CPR 1. The newborn should be dried, placed head down, gently suctioned and stimulated. 21 2. Supplemental oxygen is useful. If baby is not breathing, ventilate 40–60 breaths/min with gentle puff of air or with bag mask. 448 Clinician’s Pocket Reference, 9th Edition 3. Check apical pulse. If absent or if <60 bpm and perfusion is poor, compress at a rate of 120/min. Wrap your hands around infant’s chest and compress ¹₂–³₄ in. with thumbs side by side at the midsternum. 4. The compression/ventilation ratio is 3:1 for intubated newborn with two rescuers. Dis- continue compressions when rate reaches 80 bpm or greater. Foreign Body Obstructed Airway Sequence Adult (≥8) and Child (1–8 y) A. Conscious victim can cough, speak, breath. Do not interfere and reassure patient. Stand by and allow patient to clear partial obstruction. B. Conscious victim cannot cough, speak, breath. 1. Ask “Are you choking” or “Can you speak?” Observe for “universal distress sig- nal” for choking (hands clutched at neck). 2. Give abdominal thrusts/Heimlich maneuver. Stand behind victim. Using arms wrapped around victim, place thumb side of fist above umbilicus but below xiphoid. Give up to five subdiaphragmatic thrusts (Heimlich maneuver). 3. Reassess victim’s status, repeat Heimlich maneuvers as needed. If not improved by 1 min, activate EMS. C. Victim becomes unconscious. 1. Place in supine (face up) position. Activate EMS or if second rescuer becomes available have that person activate EMS. 2. Open airway with tongue-jaw lift; finger sweep to clear airway, open airway (head-tilt, chin-lift). 3. Give five abdominal thrusts/Heimlich maneuver astride victim. D. Victim found unconscious: Cause unknown 1. Determine unresponsiveness, call for help (activate EMS). 2. Open airway (head-tilt, chin-lift), determine breathlessness (look, listen, feel). 3. Attempt to ventilate. If unsuccessful, reposition head and reattempt. 4. If unsuccessful: a. Perform up to five Heimlich maneuvers astride victim. b. Open mouth (tongue-jaw lift); finger sweep; open airway (head-tilt, chin-lift) 5. Attempt to ventilate, if unsuccessful, repeat sequence until ventilations are effec- tive. Infant (Victim’s age, <1 y) Victim conscious 1. Verify airway obstruction (ineffective cough, no strong cry). 2. Hold child with head lower than body, give five back blows or five gentle abdominal thrusts. Repeat until victim becomes responsive. Victim becomes unconscious 1. If second rescuer is available, have that person activate EMS. 2. Open airway with tongue-jaw lift, remove foreign body if visualized. Attempt to venti- late. 21 3. If still obstructed, reposition head and attempt to ventilate. Give five back blows and five abdominal thrusts. Repeat step 2 until ventilation is effective. 4. If obstruction still not relieved after 1 min, activate EMS system. 21 Emergencies 449 Recovery Position Place an unconscious person who is still breathing and who has not suffered a traumatic neck injury in this position. 1. Kneel alongside the victim and straighten the legs. 2. Place victim’s arm that is closest to you in the “waving goodbye” position and place the other arm across the victim’s chest. 3. Grasp the far side leg above the knee and pull the thigh up toward the body. With the other hand, grasp the shoulder on the same side as the thigh. 4. Gently roll the patient toward you. Adjust the leg you are holding until both the thigh and knee are at right angles to the body. Tilt the patient’s head back and use the pa- tient’s uppermost hand to support the head and maintain a head-tilt position. 5. Continue to monitor for breathing, and call for EMS. 6. If patient stops breathing, roll on back and follow basic CPR guidelines. ADVANCED CARDIAC LIFE SUPPORT AND EMERGENCY CARDIAC CARE ACLS includes the use of advanced airway management (See Endotracheal Intubation, Chapter 13, page 268), defibrillation, and drugs along with basic CPR. Most cardiac arrests are due to VF and are unwitnessed outside the hospital setting. ACLS protocols incorporat- ing all these emergency cardiac care techniques are reviewed in the following algorithms for adults: • Universal/International ACLS algorithm (Figure 21–1) • Comprehensive emergency cardiac care algorithm (Figure 21–2) • Ventricular fibrillation and pulseless VT algorithm (Figure 21–3) • Pulseless electrical activity algorithm (Figure 21–4) • Asystole: The silent heart algorithm (Figure 21–5) • Bradycardia algorithm (Figure 21–6) • Tachycardia overview algorithm (Figure 21–7) • Narrow complex SVT algorithm (Figure 21–8) • Stable VT algorithm (Figure 21–9) • Acute coronary syndromes algorithm (Figure 21–10) • Acute pulmonary edema, hypotension, and shock (Figure 21–11) Advanced Cardiac Life Support Drugs The most commonly used agents are listed on the inside covers for quick reference. ACE Inhibitors INDICATIONS: These agents improve the outcome in post-MI patients. • Enalapril (Enalaprilat IV) SUPPLIED: Tabs 2.5, 5, 10, 20 mg; IV 1.25 mg/mL (1- and 2-mL vial) DOSAGE: .2.5 mg PO single dose, increase to 20 mg PO bid; 1.25 mg IV over 5 min, then 1.25–5.0 mg IV q6h • Captopril SUPPLIED: Caps 12.5, 25, 50, 100 mg 21 DOSAGE: 6.25 mg PO, increase to 25 mg tid and the 50 mg PO tid as tolerated (continued on page 461) 450 Clinician’s Pocket Reference, 9th Edition Adult Cardiac Arrest BLS algorithm 1 if appropriate Precordial thump if appropriate 2 Attach defibrillator/monitor Assess rhythm Check pulse +/ 3 5,6 VF/VT During CPR 4 • Check electrode/paddle positions and contact Non-VF/VT • Attempt to place, confirm, secure airway • Attempt and verify IV access Attempt • Patients with VF/VT refractory to initial shocks: defibrillation 3 — Epinephrine 1 mg IV, every 3 to 5 minutes as necessary or — Vasopressin 40 U IV, single dose, 1 time only • Patients with non-VF/VT rhythms: — Epinephrine 1 mg IV, every 3 to 5 minutes • Consider: buffers, antiarrhythmics, pacing CPR • Search for and correct reversible causes CPR 1 minute up to 3 minutes Consider causes that are potentially reversible 7 • Hypovolemia • “Tablets” (drug OD, accidents) • Hypoxia • Tamponade, cardiac • Hydrogen ion — acidosis • Tension pneumothorax • Hyper-/hypokalemia, other metabolic • Thrombosis, coronary (ACS) • Hypothermia • Thrombosis, pulmonary (embolism) FIGURE 21–1 Universal/international advanced cardiac life support algorithm. Abbreviations: VF = ventricular fibrillation; VT = ventricular tachycardia; BLS = 21 basic life support. (Reproduced, with permission, from: Circulation 2000;102 supplement 1, part 6.) 21 Emergencies 451 • Person collapses • Possible cardiac arrest • Assess responsiveness Unresponsive Begin Primary ABCD Survey 1 (Begin BLS Algorithm) • Activate emergency response system • Call for defibrillator • A Assess breathing (open airway, look, listen, and feel ) Not Breathing • B Give 2 slow breaths 1 • C Assess pulse, if no pulse • C Start chest compressions • D Attach monitor/defibrillator when available No Pulse • CPR continues • Assess rhythm VF/VT Non-VF/VT 2 3 Attempt defibrillation Non-VF/VT (up to 3 shocks if VF persists) (asystole or PEA) Secondary ABCD Survey 4,5 • Airway: attempt to place airway device • Breathing: confirm and secure airway device, ventilation, oxygenation • Circulation: gain intravenous access; give adrenergic agent; consider antiarrhythmics, buffer agents, pacing Non-VF/VT patients: — Epinephrine 1 mg IV, repeat every 3 to 5 minutes CPR for VF/VT patients: CPR up to 1 minute — Vasopressin 40 U IV, single dose, 1 time only 3 minutes or — Epinephrine 1 mg IV, repeat every 3 to 5 minutes (if no response after single dose of vasopressin, may resume epinephrine 1 mg IV push; repeat every 3 to 5 minutes) • Differential Diagnosis: search for and treat reversible causes FIGURE 21–2 Comprehensive emergency cardiac care (ECC) algorithm. Abbrevi- ations: VF = ventricular fibrillation; VT = ventricular tachycardia; BLS = basic life sup- 21 port; PEA = pulseless electrical activity. (Reproduced, with permission, from: Circulation 2000;102 supplement 1, part 6.) 452 Clinician’s Pocket Reference, 9th Edition Primary ABCD Survey 1 Focus: basic CPR and defibrillation • Check responsiveness • Activate emergency response system • Call for defibrillator A Airway: open the airway B Breathing: provide positive-pressure ventilations C Circulation: give chest compressions D Defibrillation: assess for and shock VF/pulseless VT, up to 3 times (200 J, 200 to 300 J, 360 J, or equivalent biphasic) if necessary Rhythm after first 3 shocks? Persistent or recurrent VF/VT 2 Secondary ABCD Survey Focus: more advanced assessments and treatments A Airway: place airway device as soon as possible B Breathing: confirm airway device placement by exam plus confirmation device B Breathing: secure airway device; purpose-made tube holders preferred B Breathing: confirm effective oxygenation and ventilation C Circulation: establish IV access C Circulation: identify rhythm monitor C Circulation: administer drug appropriate for rhythm and condition D Differential Diagnosis: search for and treat identified reversible causes • Epinephrine 1 mg IV push, repeat every 3 to 5 minutes 3 or • Vasopressin 40 U IV, single dose, 1 time only Resume attempts to defibrillate 1 360 J (or equivalent biphasic) within 30 to 60 seconds Consider antiarrhythmics: 4 amiodarone (llb), lidocaine (Indeterminate), magnesium (llb if hypomagnesemic state), procainamide (llb for intermittent/recurrent VF/VT). Consider buffers. Resume attempts to defibrillate 5 21 FIGURE 21–3 Ventricular fibrillation and pulseless ventricular tachycardia algo- rithm. Abbreviations: VF = ventricular fibrillation; VT = ventricular tachycardia. (Reproduced, with permission, from: Circulation 2000;102 supplement 1, part 6.) 21 Emergencies 453 Pulseless Electrical Activity (PEA = rhythm on monitor, without detectable pulse) Primary ABCD Survey Focus: basic CPR and defibrillation • Check responsiveness • Activate emergency response system • Call for defibrillator A Airway: open the airway B Breathing: provide positive-pressure ventilations C Circulation: give chest compressions D Defibrillation: assess for and shock VF/pulseless VT Secondary ABCD Survey Focus: more advanced assessments and treatments A Airway: place airway device as soon as possible B Breathing: confirm airway device placement by exam plus confirmation device B Breathing: secure airway device; purpose-made tube holders preferred B Breathing: confirm effective oxygenation and ventilation C Circulation: establish IV access C Circulation: identify rhythm monitor C Circulation: administer drugs appropriate for rhythm and condition C Circulation: assess for occult blood flow (“pseudo-EMT”) D Differential Diagnosis: search for and treat identified reversible causes Review for most frequent causes 1 • Hypovolemia • “Tablets” (drug OD, accidents) • Hypoxia • Tamponade, cardiac • Hydrogen ion — acidosis • Tension pneumothorax • Hyper-/hypokalemia • Thrombosis, coronary (ACS) • Hypothermia • Thrombosis, pulmonary (embolism) 2 Epinephrine 1 mg IV push, repeat every 3 to 5 minutes Atropine 1 mg IV (if PEA rate is slow), 3 repeat every 3 to 5 minutes as needed, to a total dose of 0.04 mg/kg FIGURE 21–4 Pulseless electrical activity algorithm. Abbreviations: VF = ventricu- lar fibrillation; VT = ventricular tachycardia; EMT = emergency medical treatment; 21 ACS = acute coronary syndrome; PEA = pulseless electrical activity. (Reproduced, with permission, from: Circulation 2000;102 supplement 1, part 6.) 454 Clinician’s Pocket Reference, 9th Edition Asystole Primary ABCD Survey 1 Focus: basic CPR and defibrillation • Check responsiveness • Activate emergency response system • Call for defibrillator A Airway: open the airway B Breathing: provide positive-pressure ventilations C Circulation: give chest compressions C Confirm true asystole D Defibrillation: assess for VF/pulseless VT; shock if indicated Rapid scene survey: any evidence personnel should not attempt resuscitation? 2,3 Secondary ABCD Survey Focus: more advanced assessments and treatments A Airway: place airway device as soon as possible B Breathing: confirm airway device placement by exam plus confirmation device B Breathing: secure airway device; purpose-made tube holders preferred B Breathing: confirm effective oxygenation and ventilation C Circulation: confirm

true asystole C Circulation: establish IV access C Circulation: identify rhythm monitor C Circulation: give medications appropriate for rhythm and condition D Differential Diagnosis: search for and treat identified reversible causes Transcutaneous pacing 4 If considered, perform immediately 5 Epinephrine 1 mg IV push, repeat every 3 to 5 minutes Atropine 1 mg IV, 6 repeat every 3 to 5 minutes up to a total of 0.04 mg/kg 7,8,9 Asystole persists Withhold or cease resuscitation efforts? • Consider quality of resuscitation? • Atypical clinical features present? • Support for cease-efforts protocols in place? 21 FIGURE 21–5 Asystole: the silent heart algorithm. Abbreviations: VF = ventricular fibrillation; VT = ventricular tachycardia. (Reproduced with permission from Circula- tion 2000;102 supplement 1, part 6) 21 Emergencies 455 Bradycardia • Slow (absolute bradycardia = rate <60 bpm) or • Relatively slow (rate less than expected relative to underlying condition or cause) Primary ABCD Survey • Assess ABCs • Secure airway noninvasively • Ensure monitor/defibrillator is available Secondary ABCD Survey • Assess secondary ABCs (invasive airway management needed?) • Oxygen–IV access–monitor–fluids • Vital signs, pulse oximeter, monitor BP • Obtain and review 12-lead ECG • Obtain and review portable chest x-ray • Problem-focused history • Problem-focused physical examination • Consider causes (differential diagnoses) 1,2 Serious signs or symptoms? Due to the bradycardia? No Yes Type II second-degree AV block 6 Intervention sequence 3,4,5 or • Atropine 0.5 to 1.0 mg Third-degree AV block? • Transcutaneous pacing if available • Dopamine 5 to 20 g/kg per minute • Epinephrine 2 to 10 g/min No Yes • Prepare for transvenous pacer 7 • If symptoms develop, use Observe transcutaneous pacemaker until transvenous pacer placed FIGURE 21–6 Bradycardia algorithm. Abbreviations: BP = blood pressure; ECG = electrocardiogram; AV = atrioventricular. (Reproduced, with permission, from: Circu- lation 2000;102 supplement 1, part 6.) 21 456 Clinician’s Pocket Reference, 9th Edition Evaluate patient • Is patient stable or unstable? • Art there serious signs or symptoms? • Are signs and symptoms due to tachycardia? Stable Unstable Stable patient: no serious signs or symptoms Unstable patient: serious signs or symptoms • Initial assessment identifies 1 of 4 types of • Establish rapid heart rate as cause of signs and tachycardias symptoms • Rate related signs and symptoms occur at many rates, seldom <150 bpm • Prepare for immediate cardioversion (see page 468) 1. Atrial fibrillation 2. Narrow-complex 3. Stable wide-complex 4. Stable monomorphic VT Atrial flutter tachycardias tachycardia: unknown type and/or polymorphic VT Evaluation focus, 4 clinical Attempt to establish a Attempt to establish a features: specific diagnosis specific diagnosis 1. Patient clinically unstable? • 12-lead ECG • 12-lead ECG 2. Cardiac function impaired? • Clinical information • Esophageal lead 3. WPW present? • Vagal maneuvers • Clinical information 4. Duration <48 or >48 hours? • Adenosine Treatment focus: clinical Diagnostic efforts yield evaluation • Ectopic atrial tachycardia 1. Treat unstable patients • Multifocal atrial tachycardia urgently • Paroxysmal supraventricular 2. Control the rate tachycardia (PSVT) 3. Convert the rhythm 4. Provide anticoagulation Treatment of Treatment of SVT Confirmed Wide-complex Confirmed Treatment of stable atrial (See narrow-complex SVT tachycardia of stable VT monomorphic fibrillation/ tachycardia algorithm) unknown type and atrial flutter polymorphic VT (See following (See stable VT: table) Preserved Ejection fraction monomorphic cardiac function <40% Clinical CHF and polymorphic algorithm) DC cardioversion DC cardioversion or or Procainamide Amiodarone or Amiodarone FIGURE 21–7 Tachycardia overview algorithm. Abbreviations: VF = ventricular 21 fibrillation; ECG = electrocardiogram; PSVT = paroxysmal supraventricular tachycar- dia; SVT = supraventricular tachycardia. (Reproduced, with permission, from: Circu- lation 2000;102 supplement 1, part 6.) 21 Emergencies 457 Narrow-Complex Supraventricular Tachycardia, Stable Attempt therapeutic diagnostic maneuver • Vagal stimulation • Adenosine • No DC cardioversion! Preserved • Amiodarone • b-Blocker • Ca 2+ channel blocker Junctional tachycardia • No DC cardioversion! EF <40%, CHF • Amiodarone Priority order: • Ca 2+ channel blocker Preserved • b-Blocker • Digoxin • DC cardioversion • Consider procainamide, amiodarone, sotalol Paroxysmal supraventricular tachycardia Priority order: EF <40%, CHF • No DC cardioversion! • Digoxin • Amiodarone • Diltiazem • No DC cardioversion! Preserved • Ca 2+ channel blocker • b-Blocker • Amiodarone Ectopic or multifocal atrial tachycardia • No DC cardioversion! EF <40%, CHF • Amiodarone • Diltiazem FIGURE 21–8 Narrow complex SVT algorithm. Abbreviations: EF = ejection frac- tion; CHF = congestive heart failure. (Reproduced, with permission, from: Circulation 2000;102 supplement 1, part 6.) 21 458 Clinician’s Pocket Reference, 9th Edition Stable Ventricular Tachycardia Monomorphic or Polymorphic? Note! Monomorphic VT Polymorphic VT May go directly to • Is cardiac function impaired? • Is QT baseline interval prolonged? cardioversion Prolonged baseline Normal baseline QT interval Normal function Poor ejection fraction QT interval (suggests torsades) Medications: any one 1 Normal baseline QT interval Long baseline QT interval 5 • Procainamide • Treat ischemia • Correct abnormal electrolytes • Sotalol • Correct electrolytes Medications: any one Others acceptable Medications: any one • Magnesium • Amiodarone • b-Blockers or • Overdrive pacing • Lidocaine • Lidocaine or • Isoproterenol • Amiodarone or • Phenytoin • Procainamide or • Lidocaine • Sotalol Cardiac function Impaired2 Amiodarone 3,4 • 150 mg IV bolus over 10 minutes or Lidocaine • 0.5 to 0.75 mg/kg IV push Then use • Synchronized cardioversion FIGURE 21–9 Stable supraventricular tachycardia algorithm. Abbreviations: VT = ventricular tachycardia. (Reproduced, with permission, from: Circulation 2000;102 supplement 1, part 6.) 21 21 Emergencies 459 Assess the initial ECG The 12-lead ECG is central to triage of ACS in the Emergency Department. Classify patients as being in 1 of 3 syndromes within 10 minutes of arrival. 1 2 3 ST-segment depression/ ST-segment elevation Nondiagnostic dynamic T-wave inversion: or new LBBB or normal ECG strongly suspicious for ischemia • ST elevation ≥1 mm in 2 or • ST depression >1 mm • ST depression 0.5 to 1.0 mm more contiguous leads • Marked symmetrical T-wave • T-wave inversion or flattening in • New or presumably new inversion in multiple precordial leads with dominant R waves LBBB (BBB obscuring leads • Normal ECG ST-segment analysis) • Dynamic ST-T changes with pain • >90% of patients with ischemic- High-risk subgroup with Heterogeneous group: rapid type chest pain and ST-segment increased mortality: assessment needed by elevation will develop new • Persistent symptoms, • Serial ECGs Q waves or positive serum recurrent ischemia • ST-segment monitoring markers for AMI. • Diffuse or widespread ECG • Serum cardiac markers • Patients with hyperacute abnormalities Future risk assessment T waves benefit when AMI • Depressed LV function helpful diagnosis is certain. Repeat • Congestive heart failure • Perfusion radionuclide imaging ECG may be helpful. • Serum marker release: • Stress echocardiography • Patients with ST depression in positive troponin or CK-MB+ early precordial leads who have posterior MI benefit when AMI diagnosis is certain. • Reperfusion therapy • Antithrombin therapy with • Aspirin • Aspirin heparin • Other therapy as appropriate • Heparin • Antiplatelet therapy with • Patients with positive serum (if using fibrin-specific lytics) aspirin markers, ECG changes, or •
-Blockers • Glycoprotein llb/llla inhibitors functional study: manage as • Nitrates as indicated •
-Blockers high risk • Nitrates FIGURE 21–10 Acute coronary syndromes algorithm. Abbreviations: ECG = elec- trocardiogram; LBBB = left bundle branch block; BBB = bundle branch block; AMI = acute myocardial infarction; MI = myocardial infarction; LV = left ventricle; CK-MB+ = positive for myocardial muscle creatine kinase isoenzyme. (Reproduced, with per- mission, from: Circulation 2000;102 supplement 1, part 6.) 21 460 Clinician’s Pocket Reference, 9th Edition Clinical signs: Shock, hypoperfusion, congestive heart failure, acute pulmonary edema Most likely problem? Acute pulmonary edema Volume problem Pump problem Rate problem Bradycardia Tachycardia See algorithm See algorithm 1st — Acute pulmonary edema Administer • Furosemide IV 0.5 to 1.0 mg/kg • Fluids • Morphine IV 2 to 4 mg • Blood transfusions • Nitroglycerin SL • Cause-specific interventions Blood • Oxygen/intubation as needed Consider vasopressors pressure? Systolic BP Systolic BP Systolic BP Systolic BP Systolic BP BP defines 2nd <70 mm Hg 70 to 100 mm Hg 70 to 100 mm Hg >100 mm Hg line of action Signs/symptoms Signs/symptoms No signs/symptoms (See below) of shock of shock of shock • Norepinephrine • Dopamine • Dobutamine • Nitroglycerin 0.5 to 30 µg/min IV 5 to 15 µg/kg per 2 to 20 µg/kg per 10 to 20 µg/min IV minute IV minute IV Consider • Nitroprusside 0.1 to 5.0 µg/kg per minute IV 2nd — Acute pulmonary edema • Nitroglycerin/nitroprusside if BP >100 mm Hg • Dopamine if BP > 70 to 100 mm Hg, signs/symptoms of shock • Dobutamine if BP >100 mm Hg, no signs/symptoms of shock Further diagnostic/therapeutic considerations • Pulmonary artery catheter • Intra-aortic balloon pump • Angiography for AMI/ischemia • Additional diagnostic studies FIGURE 21–11 Acute pulmonary edema, hypotension and shock. Abbreviations: BP = blood pressure; AMI = acute myocardial infarction. (Reproduced, with permis- sion, from: Circulation 2000;102 supplement 1, part 7) 21 21 Emergencies 461 • Lisinopril SUPPLIED: Caps 2.5, 5, 10, 20, 30, 40 mg DOSAGE: 5 mg PO within 24 h of symptoms, 5 mg after 24 h, then 10 mg over 48 h, then 10 mg PO daily for 6 wk • Ramipril SUPPLIED: Caps 1.25, 2.5, 5, 10 mg DOSAGE: 2.5 mg PO single dose, increase to 5 mg PO bid Adenosine (Adenocard) INDICATIONS: First drug for narrow-complex PSVT (not for AF or VT) SUPPLIED: 2 mg/mL in 2-mL vial DOSAGE: Adults. Put patient in reverse Trendelenburg position before administering dose; initial 6 mg over 1–3 s followed by NS bolus of 20 mL, then elevate extremity. Repeat 12 mg in 1–2 min PRN. A third dose of 12 mg in 1–2 min PRN. Peds. 0.1 mg/kg rapid IV push with continuous ECG monitoring. Follow with >5 mL NS flush. May double (0.2 mg/kg for second dose). Max: first dose: 6 mg; second dose:12 mg; single dose:12 mg Amiodarone INDICATIONS: Atrial and ventricular tachyarrhythmias and for rate control of rapid atrial arrhyth- mias in patients with impaired LV function when digoxin is ineffective SUPPLIED: 50 mg/mL in 3-mL vial DOSAGE: Adults. Max cumulative dose: 2.2 g IV/24 h. Cardiac arrest. 300 mg IV push. Consider repeating 150 mg IV push in 3–5 min. Wide-complex tachycardia (stable): Rapid inf: 150 mg IV over 10 min (15 mg/min), every 15 min PRN. Slow inf: 360 mg IV over 6 h (1 mg/min). Mainte- nance inf: 540 mg IV over 18 h (0.5 mg/min). Peds. Refractory pulseless VT, VF: 5 mg/kg rapid IV bolus. Perfusing supraventricular and ventricular arrhythmias: Loading dose: 5 mg/kg IV/IO over 20–60 min (repeat, max 15 mg/kg/day). Amrinone INDICATIONS: CHF refractory to conventional agents SUPPLIED: 0.5 mg/mL in 20-mL vial DOSAGE: Adults. 0.75 mg/kg, over 10–15 min (Do NOT mix with dextrose.). Then 5–15 µg/kg/min titrated to effect. Hemodynamic monitoring preferred. Peds. Loading dose: 0.75–1.0 mg/kg IV over 5 min; may repeat twice (Max: 3 mg/kg). Cont inf: 5–10 µg/kg/min IV Aspirin INDICATIONS: In the acute setting, administer to all patients with acute coronary syndrome (ACS) SUPPLIED: Tabs 160, 325 mg DOSAGE: 160–325 mg PO (chewing preferred ASAP onset of ACS) Atropine Sulfate INDICATIONS: First drug for symptomatic bradycardia (but not Mobitz II). Second drug (after epi- nephrine or vasopressin) for asystole or bradycardic PEA SUPPLIED: 0.1 mg/mL in 10-mL syringe (total = 1 mg). DOSAGE: Adults. Asystole or PEA: 1 mg IV push. Repeat every 3–5 min (if asystole persists) to 0.03–0.04 mg/kg max. Bradycardia: 0.5–1.0 mg IV every 3–5 min as needed; max 0.03– 0.04 mg/kg. Endotracheal administration: 2–3 mg in 10 mL NS. Peds. IV administration: 0.02 mg/kg. Min single dose: 0.1 mg, max: 0.5 mg. Max adolescent single dose: 1.0 mg. May double for second IV dose. Max child total dose: 1.0 mg. Max adolescent total dose: 2.0 mg. Endotracheal ad- ministration: 0.02 mg/kg (larger doses than IV may be required) 21 Beta Blockers INDICATIONS: All patients with suspected MI; may reduce chance of VF and reduce damage. Second line agents after adenosine, diltiazem, or digoxin to slow ventricular response in supraven- 462 Clinician’s Pocket Reference, 9th Edition tricular tachyarrhythmias. Antihypertensive for hemorrhagic and ischemic stroke. Do NOT admin- ister along with calcium channel blockers due to risk of hypotension. • Metoprolol (Lopressor) SUPPLIED: 1 mg/mL in 5-mL vial DOSAGE: Adults. 5 mg slow IV q 5

min, total 15 mg • Atenolol (Tenormin) SUPPLIED: 0.5 mg/mL in 10-mL amp DOSAGE: Adults. 5 mg slow IV (over 5 min). In 10 min, second dose 5 mg slow IV. In 10 min, if tolerated, start 50 mg PO, then 50 mg PO bid • Propanolol (Inderal) SUPPLIED: 1.0 mg/mL in 1 amp, 4 mg/mL in 5-mL DOSAGE: Adults. 0.1 mg/kg slow IV push, divided 3 equal doses 2–3 min intervals, max 1 mg/min. Repeat after 2 min, PRN • Esmolol (Brevibloc) SUPPLIED: 10 mg/mL in 10-mL amp DOSAGE: Adults. 0.5 mg/kg over 1 min, then 0.05 mg/kg/min • Labetalol SUPPLIED: 5 mg/mL (Amps 20, 40, 60 mL) DOSAGE: 10 mg IV push over 1–2 min. Repeat or double dose every 10 min (max: 150 mg); or initial bolus, then 2–8 µg/min Calcium Chloride INDICATIONS: Known/suspected hyperkalemia, hypocalcemia (eg, multiple transfusions), antidote for calcium channel blocker overdose, prophylactically before IV calcium channel blockers (pre- vent hypotension) SUPPLIED: 100 mg/mL in 10-mL vial (total = 1 g; 10% solution) DOSAGE: Adults. 8–16 mg/kg (usually 5–10 mL) IV slow push for hyperkalemia and calcium channel blocker overdose. 2–4 mg/kg (usually 2 mL) IV before IV calcium blockers. Peds. 20 mg/kg (0.2–0.25 mL/kg) slow push. Repeat PRN Calcium Gluconate SUPPLIED: 10% = 100 mg/10 mL = 9 mg/mL Ca DOSAGE: Peds. 60–100 mg/kg (0.6–1.0 mL/kg) IV slow push. Repeat for documented conditions Digibind Digoxin-specific antibody therapy INDICATIONS: Digoxin toxicity with uncontrolled life-threatening arrhythmias, shock, CHF; hyper- kalemia >5 mEq/L with serum dig levels above 10–15 ng/mL SUPPLIED: 40-mg vial (each vial binds about 0.6 mg digoxin) DOSAGE: Adults. Chronic intoxication: 3–5 vials may be effective. Acute overdose: See Chapter 22; based on dose ingested (average dose is 10 vials (400 mg), but may require up to 20 vials (800 mg). Digoxin 21 SUPPLIED: 0.15 mg/mL or 0.1 mg/mL in 1- or 2-mL amp INDICATIONS: Slow ventricular response in AF or atrial flutter. Second-line for PSVT DOSAGE: Adults. Loading 10–15 µg/kg. Maintenance dose see Chapter 22. 21 Emergencies 463 Diltiazem (Cardizem) INDICATIONS: Control ventricular rate in AF and atrial flutter. Use after adenosine to treat refrac- tory PSVT in patients with narrow QRS complex and adequate BP. SUPPLIED: 5 mg/mL in 5- or 10-mL vial (total = 25 or 50 mg) DOSAGE: Adults. Acute rate control: 15–20 mg (0.25 mg/kg) IV over 2 min. Repeat in 15 min at 20–25 mg (0.35 mg/kg) over 2 min. Maintenance: 5–15 mg/h, titrated to heart rate Dobutamine (Dobutrex) INDICATIONS: Pump problems with BP 70–100 mm Hg and no signs of shock SUPPLIED: 12.5 mg/mL in 20-mL vial (total = 250 mg). IV inf: Dilute 250 mg (20 mL) in 250 mL NS or D5W DOSAGE: Adults. 2–20 µg/kg/min; titrate heart rate not >10% of baseline. Hemodynamic monitor- ing recommended. Peds. Cont IV inf: Titrate to effect (initial dose 5–10 µg/kg/min). Typical inf dose: 2–20 µg/kg/min Dopamine (Intropin) INDICATIONS: Second line for symptomatic bradycardia. Hypotension (BP <70–100 mm Hg) with signs of symptoms of shock SUPPLIED: 40 mg/mL or 160 mg/mL. IV inf: Mix 400–800 mg in 250 mL NS or D5W. DOSAGE: Adults. Titrate to response. Low: 1–5 µg/kg/min (“renal doses”). Moderate: 5– 10 µg/kg/min (“cardiac doses”). High: 10–20 µg/kg/min (“vasopressor doses”). Peds. Titrate to ef- fect. Initial, 5–10 µg/kg/min; typical: 2–20 µg/kg/min Note: If >20 µg/kg/min is required, consider use of alternative adrenergic agent (eg, epinephrine) Epinephrine INDICATIONS: Cardiac arrest: VF, pulseless VT, asystole, PEA. Symptomatic bradycardia: After atropine and transcutaneous pacing. Anaphylaxis, severe allergic reactions: Combine with large fluid volumes, corticosteroids, antihistamines. SUPPLIED: 1.0 mg/10 mL in preloaded 10-mL syringe (total = 1 mg), 1 mg/mL in glass 1-mL amp (total = 1 mg) DOSAGE: Adults. Cardiac arrest: IV dose: 1.0 mg IV push, repeat every 3–5 min; doses up to (0.2 mg/kg) if 1 mg dose fails. Inf: 30 mg epinephrine (30 mL of 1:1000 solution) to 250 mL NS or D5W, run at 100 mL/h, titrate. Endotracheal: 2.0–2.5 mg in 20 mL NS. Profound bradycardia/hy- potension: 2–10 µg/min (1 mg of 1:1000 in 500 mL NS, infuse 1–5 mL/min). Peds. Asystole, pulseless arrest: First dose: 0.1 mg/kg IV (0.1 mL/kg of 1:10,000 “standard concentration”). Sec- ond and subsequent doses: 0.1 mg/kg IV (0.1 mL/kg of 1:1000 “High” concentration. Administer every 3–5 min during arrest; up to 0.2 mg/kg may be effective. Endotracheal: 0.1 mg/kg (0.1 mL/kg of 1:1000 [“high”] concentration) continue q3–5 min of arrest until IV access is achieved; then begin with first IV dose. Symptomatic bradycardia: 0.01 mg/kg IV (0.1 mL/kg of 1:10,000 [“stan- dard”] concentration). Endotracheal doses: 0.1 mg/kg (0.1 mL/kg of 1:1000 [“high”] concentra- tion). Cont IV inf: Begin with rapid infusion; then titrate to response. Typical inf: 0.1– 1.0 µg/kg/min (Higher doses may be effective) Flumazenil (Romazicon) INDICATIONS: Reverse benzodiazepine toxicity (do NOT use in tricyclic overdose or in unknown poisoning) SUPPLIED: 0.1 mg/mL in 5- and 10-mL vials DOSAGE: Adults. 0.2 mg IV over 15 s then 0.3 mg IV over 30 s, if no response, give third dose. Third dose: 0.5 mg IV given over 30 s, repeat once per min until response, or total of 3 mg. Furosemide (Lasix) INDICATIONS: Acute pulmonary edema in BP >90–100. Hypertensive emergencies or increased in- 21 tracranial pressure SUPPLIED: 10 mg/mL in 2-, 4-, and 10-mL amp or vials 464 Clinician’s Pocket Reference, 9th Edition DOSAGE: Adults. 0.5–1.0 mg/kg over 1–2 min. If no response, double the dose to 2.0 mg/kg over 1–2 min Glucagon INDICATIONS: Reverse effects of calcium channel blocker or beta-blocker SUPPLIED: 1- and 10-mg vials DOSAGE: Adults. 1–5 mg over 2–5 min Glucoprotein IIb/IIIa inhibitors INDICATIONS: Acute coronary syndromes without ST elevation. Do NOT use with history of active bleeding or surgery within 30 d or if platelets <150,000/mm3. Note that optimum dosing and dura- tion not established; check package insert. • Abciximab (ReoPro) SUPPLIED: 2 mg/mL in 5-mL vial DOSAGE: ACS with planned PCI within 24 h: 0.25 mg/kg IV bolus up to 1 h before proce- dure, then 0.125 µg/kg/IV; must use with heparin. Platelet recovery within 48 h; redosing may cause hypersensitivity reaction. • Eptifibatide (Integrilin) SUPPLIED: 0.75 and 2 mg/mL in 10-mL vial DOSAGE: ACS: 180 µg/kg IV bolus then 2 µg/kg/min infusion PCI: 135 µg/kg IV bolus then 0.5 µg/kg/min infusion; repeat bolus in 10 min. • Tirofiban (Aggrastat) SUPPLIED: 250 µg/mL in 50 mL or premixed 50 µg/mL DOSAGE: ACS or PCI: 0.4 µg/kg/min IV for 30 min, then 0.1 µg/kg/min inf Heparin (Unfractionated) INDICATIONS: Adjuvant therapy in AMI. Begin heparin with fibrinolytics. SUPPLIED: 0.5–1.0 mL amp, vials, and prefilled syringes. Multidose vials 1, 2, 5 and 30 mL. Con- centrations range from 1000 to 40,000 IU/mL. DOSAGE: Adults. Bolus 60 IU/kg (max bolus: 4000 IU). Continue 12 IU/kg/h (max 1000 IU/h for patients >70 kg) round to the nearest 50 IU. Adjust to maintain PTT 1.5–2.0 × control values for 48 h or until angiography. Heparin (Low Molecular Weight) (Fragmin, Lovenox) INDICATIONS: ACS with non-Q wave or unstable angina SUPPLIED: Dalteparin (Fragmin), Enoxaparin (Lovenox) DOSAGE: 1 mg/kg bid SQ for 2–8 d with aspirin Ibutilide INDICATIONS: Supraventricular arrhythmias (AFiB, A flutter); short-acting SUPPLIED: 1 mg/10 mL DOSAGE: 1 mg IV over 10 min (if <60 kg 0.01 mg/kg) Isoproterenol (Isuprel) 21 INDICATIONS: Torsades de pointes unresponsive to magnesium sulfate. Temporary control of bradycardia in heart transplant patients. Class IIb at low doses for symptomatic bradycardias SUPPLIED: 0.1 mg/mL in 1-mL vial. IV inf: Mix 1 mg in 250 mL NS or D5W. DOSAGE: Adults. 2–10 µg/min. Titrate to effect. 21 Emergencies 465 Lidocaine INDICATIONS: Cardiac arrest from VF/VT. Stable VT, wide-complex tachycardias of uncertain type, wide-complex PSVT SUPPLIED: 20 mg/mL in preloaded 5-mL syringe, 10 mg/mL in 5-mL vial. Can be given via endo- tracheal tube. DOSAGE: Adults. Cardiac arrest from VF/VT: Initial dose: 1.0–1.5 mg/kg IV. For refractory VF may give additional 0.5–0.75 mg/kg IV push, repeat in 5–10 min, max total dose is 3 mg/kg. A single dose of 1.5 mg/kg IV in cardiac arrest is acceptable. Endotracheal administration: 2– 4 mg/kg. Perfusing arrhythmia: For stable VT, wide-complex tachycardia or uncertain type, signifi- cant ectopy, use as follows: 1.0–1.5 mg/kg IV push. Repeat 0.5–0.75 mg/kg every 5–10 min; max total dose, 3 mg/kg. Maintenance inf: 1–4 mg/min (30–50 µg/min) Magnesium Sulfate INDICATIONS: Cardiac arrest associated with torsades de pointes or suspected hypomagnesemic state, refractory VF, life-threatening ventricular arrhythmias due to digitalis toxicity, tricyclic over- dose. Consider prophylactic administration in hospitalized patients with AMI. SUPPLIED: Amps 2 and 10 mL of 50% MgSO4 (total = 1 g and 5 g). 10 mL in preloaded syringe (total = 5 g/10 mL) DOSAGE: Adults. Cardiac arrest: 1–2 g IV push (2–4 mL of a 50% solution) diluted in 10 mL of D5W. AMI: Loading dose of 1–2 g, mixed in 50–100 mL of D5W, over 5–60 min IV. Follow with 0.5–1.0 g/h IV for up to 24 h. Torsades de pointes: Loading dose of 1–2 g mixed in 50–100 mL of D5W, over 5–60 min IV. Follow with 1–4 g/h IV (titrate dose to control the torsades). Mannitol INDICATIONS: Increased intracranial pressure in management of neurologic emergencies SUPPLIED: 150-, 250-, and 1000-mL IV containers (strengths: 5%, 10%, 15%, 20%, and 25%). DOSAGE: Adults. Administer 0.5–1.0 g/kg over 5–10 min. Additional doses of 0.25–2g/kg can be given every 4–6 h as needed. Use in conjugation with oxygenation and ventilation. Morphine Sulfate INDICATIONS: Chest pain and anxiety associated with AMI or cardiac ischemia, acute cardiogenic pulmonary edema (if blood pressure is adequate) SUPPLIED: 2–10 mg/mL in a 1-mL syringe DOSAGE: Adults. 2–4 mg IV (over 1–5 min) every 5–30 min Naloxone (Narcan) INDICATIONS: To reverse effects of narcotic toxicity, including respiratory depression, hypotension, and hypoperfusion DOSAGE: Adults. 0.4–2.0 mg IV every 2 min; up to 10 mg over <30 min. Peds. Bolus IV dose: For total reversal of narcotic effects (smaller doses may be used if total reversal not required), as fol- lows: Birth–5 y (≤ 10 kg): 0.1 mg/kg. ≥5 y (>20 kg): 2.0 mg. May be necessary to repeat doses fre- quently. Cont inf: 0.04–0.16 mg/kg/h Nitroglycerin INDICATIONS: Chest pain of suspected cardiac origin; unstable angina; complications of AMI, in- cluding CHF, left ventricular failure; HTN crisis or urgency with chest pain SUPPLIED: Parenteral: Amps: 5 mg in 10 mL, 8 mg in 10 mL, 10 mg in 10 mL, vials: 25 mg in 5 mL, 50 mg in 10 mL, 100 mg in 10 mL. SL tabs: 0.3 and 0.4 mg. Aerosol spray: 0.4 mg/dose DOSAGE: Adults. IV bolus: 12.5–25 µg. Infuse at 10–20 µg/min. Route of choice for emergencies. Use IV sets provided by manufacturer. SL route: 0.3–0.4 mg, repeat every 5 min. Aerosol spray: Spray for 0.5–1.0 s at 5-min intervals. 21 Nitroprusside (Sodium Nitroprusside, Nipride) INDICATIONS: HTN crisis, reduce afterload in CHF and acute PE 466 Clinician’s Pocket Reference, 9th Edition SUPPLIED: 50-mg amp, mix in 250 mL D5W only (keep covered with opaque material) DOSAGE: 0.10 µg/kg/min, titrate up to 5.0 µg/kg/min. Use infusion pump; hemodynamic monitor- ing for optimal safety Norepinephrine INDICATIONS: Severe cardiogenic shock and significant hypotension. Last resort for ischemic heart disease and shock SUPPLIED: 1 mg/mL in 4-mL amp. Mix 4 mg in 250 mL of D5W or D5NS DOSAGE: Adults. 0.5–1.0 µg/min titrated to 30 µg/min. Peds. IV inf: Initial 0.1–2 µg/kg/min to ef- fect. Do NOT administer with alkaline solutions. Procainamide (Pronestyl) INDICATIONS: Recurrent VT not controlled by lidocaine, refractory PSVT, refractory VF/pulseless VT, stable wide-complex tachycardia of unknown origin, AF with rapid rate in WPW SUPPLIED: 100 mg/mL in 10-mL vial, 500 mg/mL in 2-mL vial DOSAGE: Adults. Recurrent VF/VT: 20 mg/min IV (max total 17 mg/kg). In urgent situations up to 50 mg/min to a total dose of 17 mg/kg. Other indications: 20 mg/min IV until one of the following occurs: arrhythmia suppression, hypotension, QRS widens by more than 50%, total dose of 17 mg/kg is given. Maintenance: 1–4 mg/min Sodium Bicarbonate INDICATIONS: Specific indications for bicarbonate use are as follows: Class I (usually indicated) if known preexisting hyperkalemia. Class IIa (accepted, possibly controversial) if known preexisting bicarbonate-responsive acidosis (eg, DKA); tricyclic antidepressant overdose; alkalinize urine in aspirin overdose. Class IIb (accepted, but may not help, probably not harmful) if prolonged resusci- tation with effective ventilation; on return of spontaneous circulation after long

arrest interval. Class III (harmful) in hypoxic lactic acidosis (eg, cardiac arrest and CPR without intubation) SUPPLIED: 50-mL syringe (8.4% sodium bicarbonate provides 50 mEq/50 mL) DOSAGE: Adults. IV inf: 1 mEq/kg IV bolus. Repeat half this dose every 10 min thereafter. If rapidly available, use ABG analysis to guide therapy. Sodium Bicarbonate (Pediatric) INDICATIONS: Severe metabolic acidosis (documented or following prolonged arrest) unresponsive to oxygenation and hyperventilation, hyperkalemia, tricyclic antidepressant toxicity DOSAGE: Adults. 8.4% 1 mEq/mL in 10- or 50-mL syringe, 4.2% 0.5 mEq/mL in 10-mL syringe. Peds. 1 mEq/kg. Dose may be calculated to correct ¹₄–¹₂ of base deficit. Thrombolytic Agents (Fibrinolytic Agents) INDICATIONS: AMI in adults: ST-segment elevation of 1 mm or more in at least two contiguous leads in the setting of AMI. Adjuvant therapy: 60–325 mg aspirin chewed as soon as possible. Begin heparin immediately and continue for 48 h if alteplase is used. • Alteplase, Recombinant SUPPLIED: Vials 20, 50, and 100 mg, reconstituted with sterile water to 1 mg/mL DOSAGE: Adults. Recommended dose based on patient’s weight, not to exceed 100 mg. AMI: Accelerated inf: Give 15 mg bolus. Then 0.75 mg/kg over next 30 min (not to exceed 50 mg). Then 0.50 mg/kg over next 60 min (not to exceed 35 mg). 3-h inf: 60 mg in first hour (initial 6–10 mg as a bolus). Then 20 mg/h for 2 additional hours. Acute ischemic stroke: 0.9 mg/kg (max 90 mg) infused over 60 min. 10% of total dose as initial IV bolus over 1 min. Give the remaining 90% over the next 60 min. 21 • Streptokinase SUPPLIED: Reconstitute to 1 mg/mL DOSAGE: Adults. 1.5 million IU in a 1-h infusion 21 Emergencies 467 • Anistreplase APSAC SUPPLIED: Reconstitute 30 U in 50 mL water or D5W. Use two peripheral IV lines, one ex- clusively for thrombolytic administration. DOSAGE: Adults. 30 IU IV over 2–5 min • Reteplase, recombinant (Retavase) SUPPLIED: 10-U vials reconstituted with sterile water to 1 U/mL DOSAGE: Adults. 10 U IV bolus over 2 min. 30 min later, give second 10 U IV bolus over 2 min. NS flush before and after each bolus Verapamil (Colan, Isoptin) INDICATIONS: Second line for PSVT with narrow QRS complex and adequate BP SUPPLIED: 2.5 mg/mL in 2-, 4-, and 5-mL vials (totals = 5, 10, and 12.5 mg) DOSAGE: Adults. 2.5–5.0 mg IV over 1–2 min. Repeat 5–10 mg, if needed, in 15–30 min (30 mg max). Alternative: 5 mg bolus every 15 min to total dose of 30 mg Electrical Defibrillation and Cardioversion Although the defibrillator is the basic piece of equipment for both defibrillation and car- dioversion, they are two distinctly different procedures. New devices include shock advisory defibrillators (automated external defibrillators). The energy level is the watt-second or joule. Standard Defibrillation Procedure (conventional device) 1. This is the primary therapy for VF or pulseless VT. Asystole is not now routinely defib- rillated. 2. Use paste or pads on skin (see step 3 for location). 3. Shout “Charging defibrillator-stand clear,” synchronization switch off (if on, the de- fibrillator may not fire). In adults, energy levels begin at 200 J. In children, use 2 J/kg advance to 6 J/kg max. 4. Place paddles as directed on the handles: one at the right upper sternum and one at the left anterior axillary line (apex). 5. Apply paddles with firm pressure (approximately 25 lb). 6. Shout “I am going to shock on three. Stand clear!” and make sure no one is touching the patient or bed including yourself. 7. Shout “Clear,” and visually check for other team members. 8. Shout three times “Everybody clear,” and press both paddle buttons simultaneously to fire the unit, and observe for any change in the dysrhythmia. 9. Defibrillate up to three times with increasing joules (200, >200–300, >360). If these fail to convert, continue full output (360 J) for all future shocks. If VT recurs, shock again at last energy level. 10. If a patient is HYPOTHERMIC (Core temperature < 30 °C) shock only three times as in step 8. Resume shocks only after temperature rises above 30 °C. 11. If patient has automated implantable defibrillator and device is delivering shocks, wait 60 s for cycle to complete. If defibrillation attempted, place paddles several inches from the implanted pacer unit. Automated External Defibrillator (AED) 21 1. Familiarize yourself with the features of the unit well in advance of using it. These computerized devices “analyze” the rhythm and indicate if a shock is appropriate. 468 Clinician’s Pocket Reference, 9th Edition 2. Place the pads on the patient (upper right sternum and cardiac apex). Press the “ana- lyze” button. 3. If appropriate (VT or VF), the unit charges and the “shock” sign is given. 4. Announce “Shock is indicated . . . Stand clear,” and verify that no one is touching pa- tient. Depress “shock” button to administer shock. 5. Repeat until arrhythmia is cleared (“no shock indicated” signal will flash). In gen- eral, shock in sets of three without interposing CPR. After three shocks, do 1 min of CPR. Cardioversion Used for VT with a pulse, atrial arrhythmias with rapid ventricular response (PAT, AF, or atrial flutter); an attempt to slow the heart or convert rhythm. Procedure is like that for de- fibrillation, except: 1. Consider sedation because most of these patients are conscious. Agents can include diazepam, midazolam with or without a narcotic such as morphine, or fentanyl. Anes- thesia support is helpful if readily available. 2. Start with lower energy levels than for defibrillation. Start at 100 J and increase to 200, 300, and finally 360. 3. Keep the synchronizer switch on (prevents shocking during vulnerable part of QRS complex when shock may cause VF, so-called R-on-T phenomenon). Observe for the markers on the R waves indicating that the synch mode is engaged. 4. Place paddles, apply pressure, and verify area is cleared as for the defibrillation steps. 5. Most defibrillators default back to the unsynchronized mode to allow rapid shock in case of VF. Reset synch mode if multiple cardioversions needed. Transcutaneous Pacing Primarily used for hemodynamically unstable bradycardia. External pacemakers can be set in the asynchronous (nondemand or fixed mode) or demand mode in the range of 30–180 bpm with current outputs from 0–200 mA. 1. Place electrode pads on chest as per unit’s instructions. 2. Turn unit on and set pacer to 80 bpm initially. 3. Adjust current upward until capture is achieved (ie, wide QRS after each pacer spike on ECG for bradycardia. 4. For asystole (not routinely used) begin at full output. If capture occurs, decrease to threshold and increase by 2 mA. OTHER COMMON EMERGENCIES The following material gives the treatment for other common emergencies. Dosages are for adults unless stated otherwise. Anaphylaxis Systolic BP <90 mm Hg 21 Epinephrine DOSAGE: Adults. IV bolus: 100 µg of 1:10,000 over 5–10 min. IV inf: 1–4 µg/min. Peds. IV inf: 0.1–0.3 µg/kg/min, max 1.5 µg/kg/min 21 Emergencies 469 Systolic BP >90 mm Hg • Epinephrine DOSAGE: 1:1000 soln SQ. Adults. 0.3–0.5 mL. Peds. 0.01 mL/kg, max 0.5 mL Supplemental drugs for anaphylaxis include: • Diphenhydramine DOSAGE: Adults. IV/IM/PO 50 mg. Peds. IV/IM/PO 1 mg/kg • Methylprednisolone DOSAGE: 1–2 mg/kg IV • Ranitidine (Zantac) DOSAGE: Adults. IV 50 mg over 5 min. Peds. IV 0.5mg/kg over 5 min • Albuterol DOSAGE: Adults. 2.5 mg nebulized. Peds. 1.25 mg nebulized Asthmatic Attack Mild Albuterol (Nebulized) DOSAGE: Adults. 2.5–5.0 mg at 20 min for 3 doses. Peds. 1.25–2.5 mg at 20 min for 3 doses Moderate to Severe Ipratropium Bromide (nebulized) DOSAGE: Adults. 0.5 mg with first albuterol treatment. Peds. 250 µg with first albuterol treatment. Methylprednisolone DOSAGE: Adults. 1 mg/kg IV. Peds. 2 mg/kg IV Severe Epinephrine NOTE: Administer SQ or aerosolized beta agonists as for mild to moderate cases Aminophylline NOTE: Administer as for mild to moderate cases. Give early consideration to Hydrocortisone sodium DOSAGE: 4 mg/kg IV q2–4h or Methylprednisolone DOSAGE: 2–4 mg/kg IV q4h Anticholinergic Crisis 21 Usually related to drug overdose. Patients present “red as a beet, mad as a hatter, hot as a furnace, dry as a bone, blind as a bat.” 470 Clinician’s Pocket Reference, 9th Edition Physostigmine DOSAGE: 0.5–2.0 mg IV NOTE: Administer S-L-O-W-L-Y (may cause seizures if given rapidly). Have cardiac monitor at- tached and resuscitation equipment at the bedside. Coma 1. Establish/secure airway. 2. Protect cervical spine. 3. Assess for respiratory failure and shock (ACLS). 4. Supply oxygen, IV access, cardiac monitor, and pulse oximetry. 5. Administer 1 amp (50 mL) of D50 IV manually; some recommend checking a stat glu- cose first 6. Administer 100 mg thiamine IV. 7. Give naloxone (Narcan) (see following section on Narcotics Overdose). 8. Obtain fingerstick glucose, SMA, CBC, urinalysis, and ABG. Dental Emergencies Not including facial fractures, there are generally two major categories of dental emergen- cies: toothaches with associated abscesses and avulsed (knocked-out) teeth. Most toothaches may be managed with antibiotics (usually penicillin-V 500 mg, q6h) and anal- gesics until proper dental attention can be obtained. Fluctuant abscesses may be drained if convenient. The exception to this rule is submandibular or infraorbital swelling. With sub- mandibular infections, Ludwig’s angina may develop, a life-threatening occurrence. These patients should be held for observation with special attention to maintaining the airway until a dental consult can be obtained. Infraorbital infections can lead to a cavernous sinus throm- bosis if allowed to progress. Avulsed teeth may or may not have an associated dentoalveolar fracture. The best treat- ment is to reposition the displaced tooth back in the socket within 30 min or as soon as pos- sible. If the tooth root is dirty, wash it gently with sterile saline. Do not scrub or scrape the root. Get a dental consult to arrange to have the tooth splinted back in the socket. Hypercalcemia See Chapter 9, page 188 Hyperkalemia See Chapter 9, page 186 Hypertensive Crisis 1. Treat only if signs of end organ damage. 2. MAP should not be reduced more than 20–25% over 30–60 min. MAP = 1 [ (SBP − DBP) + DBP] 3 • Labetalol 21 DOSAGE: 20 mg IV bolus then 2 mg/min IV to target BP or • Sodium Nitroprusside DOSAGE: 0.5 µg /kg/min ↑ to max (10 µg/kg) min 21 Emergencies 471 Hypoglycemia 1. Draw a STAT serum glucose. Do not wait for result before treating if hypoglycemia is strongly suspected. A finger Dextro stick can usually be quickly checked. 2. Give orange juice with sugar if the patient is awake and alert; if not, give 1 amp of D50 IV (Peds. 1 mL/kg). 3. If IV access is not possible, give glucagon 1 mg IM or SC. Narcotics Overdose Naloxone (Narcan) DOSAGE: Adults. 0.4–0.8 mg IV or IM, repeat as needed. (Note: if you suspect the patient is a nar- cotic addict give 0.4 mg instead and repeat as needed to avoid precipitating severe withdrawal. Peds. 0.01–0.02 mg/kg IV or IM, repeat as needed. Observe patient for at least 6 h after treatment. Poisoning 1. Support airway, respiration, and circulation, as needed. 2. Determine ingested substance; give specific antidote, if available. The following is a list of some common poisons with their antidotes (Dosages for adults, unless otherwise specified): Acetaminophen N-acetylcysteine, 140 mg/kg Anticholinesterases Atropine 0.5–2 mg IV; may need up to (organophosphates, physostigmine) 5 mg IV q 15 min if severe, then 70 mg/kg × 17 more doses; 0.05 mg/kg IV in children Benzodiazepines Flumazenil (see page 463) Beta-blockers Glucagon 0.05 mg/kg IV bolus for BP <90, then infusion of 75–150 mg/kg/h Carbon monoxide High-flow oxygen Calcium channel blockers Calcium chloride 10–20 mL/kg of 1% solution then 20 mg/kg/h Cyanide Amyl nitrate pearls inhale every 2 min then sodium nitrite 10 mL 3% IV over 3 min (0.33 mL/kg of 3% solution in children) or sodium thiosulfate 50 mL of 25% solution over 10 min or 1.65 mL/kg in children Cyclic antidepressants NaHCO3 3 amps (50 mg/50 mL) in 1 L D5W @ 2–3 mL/kg/h Digoxin Digoxin-specific Fab Number of vials = Patient' s weight (kg) Seru m digoxin level × 100 Methanol, ethylene glycol Loading dose 1 g/kg of a 10% solution slowly IV, followed by an infusion of 130 mg/kg/h. If patient is on dialysis give 250–300 mg/kg/h to maintain levels. 21 Opiates, narcotics Naloxone see page 465.

3. Prevent further absorption as described if conscious/unconscious 472 Clinician’s Pocket Reference, 9th Edition Unconscious Patient • Protect airway with an endotracheal tube. • Lavage with an Ewald tube or 28 French or larger NG tube, if ingestion occurred, 1 h. • Use 300 mL NS boluses at a time through the NG or Ewald tube for adults and 20 mL/kg in children. • Activated charcoal can be added, unless an oral antidote is to be given. • Cathartics (sorbitol or magnesium citrate) promote GI elimination. Conscious Patient • Activated charcoal 1 g/kg, Contraindicated for iron, lithium, lead, alkali, acid. Also give 70% sorbitol solution (2 mL/kg body weight). Anyone given sorbitol should be monitored for hypokalemia and hypomagnesemia. • Attempt to promote excretion through IV hydration. • Alkalinization (0.5–1 mEq/kg/L in IV fluids) for salicylates, barbiturates, tricyclics Shock See also Chapter 20, page 431, and this chapter, page 460. Hypovolemic: Initially, use isotonic fluids such as NS or lactated Ringer’s, blood, albu- min, Plasmanate, or hetastarch. Seizures/Status Epilepticus Status epilepticus refers to >1 min of continuous seizure activity or back-to-back seizures without recovery in between. Initial Supportive Care • Maintain airway with C-spine precautions. • Deliver oxygen by nasal cannula. • Monitor ECG and blood pressure. • Maintain normal temperature. Pharmacologic Therapy See Table 21–1. • Establish IV. • Administer thiamine 100 mg IV. • Administer 1 amp of D50 IV in an adult (2 mL/kg D25 in children) unless obviously hyperglycemic. • Administer lorazepam or diazepam initially (see Table 21–1) (midazolam 0.2 mg/kg) can be given IM in children if no IV. • If seizures persist, give fosphenytoin or phenytoin (see Table 21–1). • If seizures persist, administer phenobarbital, paraldehyde. • If still no response, obtain emergency neurosurgical and anesthesiology consultation. 21 21 Emergencies 473 TABLE 21–1 Drugs for the Emergency Treatment of Seizures Pediatric Maximum Dose Adult Rate Drug (mg/kg) Dose (mg/min) Diazepam (Valium) 0.10–0.20 IV 5–10 mg IV 3–5 (up to 30 mg) Fosphenytoin N/A 20 mg/kg IV 150 Paraldehyde 0.15–0.3 30 mL PR* NA mL/kg PR* Phenytoin (Dilantin)† 15 IV Same as for child 50 Phenobarbital‡ 10 IV or IM 120–140 mg IV 100 *When given rectally, mix 2:1 with cottonseed or olive oil. †When given IV, use a maximum dose of 50 mg/min and monitor ECG and vital signs closely. Can cause severe hypotension and bradycardia. Mix with NS to prevent precipi- tation. ‡Indicated when the patient is allergic to phenytoin. Patients may require intubation. 21 This page intentionally left blank. 22 COMMONLY USED MEDICATIONS Introduction Hematologic Agents Classification Immune System Agents Allergy Treatments Musculoskeletal Agents Antidotes OB/GYN Agents Antimicrobial Agents Pain Relievers Antineoplastic Agents Respiratory Agents Cardiovascular Agents Urinary/Genitourinary Agents Central Nervous System Agents Wound Care Dermatologic Agents Miscellaneous Agents Dietary Supplements Generic Drug Listing and Data Ear (Otic) Agents Aminoglycoside Dosing Endocrine System Immunization Schedule Eye (Ophthalmic) Agents Gastrointestinal Agents INTRODUCTION This section is a quick reference of commonly used medications with selected key data listed for each drug. Be familiar with all the indications, contraindications, adverse effects, and drug interactions of any medication you prescribe. Such detailed information is beyond the scope of this manual but can be found in the package insert, the Physicians’ Desk Refer- ence (PDR), or from the American Hospital Formulary Service. Medications are listed by class, and then the individual medications are listed in alpha- betical order by generic name. Some of the more common trade names are listed (in paren- theses after the generic name) for each medication. Because many medications are used to treat various conditions based on the medical literature and not listed in their package insert, we list common uses of the medication rather than the official “labeled indications” (FDA approved). If no pediatric dosage is provided, we assume the agent is not well established for this age group. Medications under the control of the U.S. Drug Enforcement Agency (Schedule I–V controlled substances) are indicated by the symbol [C]. The following is a general descrip- tion for the schedules of controlled substances: • Schedule I: All nonresearch use forbidden (eg, heroin, LSD, mescaline, etc) • Schedule II: High addictive potential; medical use accepted. No telephone call-in prescriptions; no refills. Some states require special prescription form (eg, cocaine, morphine, methadone) • Schedule III: Low to moderate risk of physical dependence, high risk of psycholog- ical dependence; prescription must be rewritten after 6 months or five refills (eg, ac- etaminophen plus codeine) 22 475 Copyright 2002 The McGraw-Hill Companies, Inc. Click Here for Terms of Use 476 Clinician’s Pocket Reference, 9th Edition • Schedule IV: Limited potential for dependence; prescription rules same as for Schedule III (eg, benzodiazepines) • Schedule V: Very limited abuse potential; prescribing regulations often same as for uncontrolled medications, some states have additional restrictions CLASSIFICATION Allergy Treatments Antihistamines Cetirizine Cyproheptadine Hydroxyzine Chlorpheniramine Diphenhydramine Loratadine Clemastine fumarate Fexofenadine Miscellanous Agents Budesonide Cromolyn Antidotes Acetylcysteine Digoxin immune FAB Naloxone Amifostine Flumazenil Physostigmine Charcoal Ipecac syrup Succimer Dexrazoxane Mesna Antimicrobial Agents Antibiotics Aminoglycosides Amikacin Neomycin Tobramycin Gentamicin Streptomycin Cephalosporins, First-Generation Cefadroxil Cephalexin Cephapirin Cefazolin Cephalothin Cephradine Cephalosporins, Second-Generation Cefaclor Cefotetan Cefuroxime Cefmetazole Cefoxitin Loracarbef Cefonicid Cefprozil Cephalosporins, Third-Generation Cefdinir Cefotaxime Ceftizoxime Cefixime Cefpodoxime Ceftriaxone Cefoperazone Ceftazidime Cephalosporins, Fourth-Generation Cefepime 22 22 Commonly Used Medications 477 Fluoroquinolones Ciprofloxacin Lomefloxacin Ofloxacin Gatifloxacin Moxifloxacin Levofloxacin Norfloxacin Macrolides Azithromycin Dirithromycin Erythromycin and sulfi- Clarithromycin Erythromycin soxazole Penicillins Amoxicillin Mezlocillin Penicillin V Amoxicillin-clavulanate Nafcillin Piperacillin Ampicillin Oxacillin Piperacillin-tazobactam Ampicillin-sulbactam Penicillin G aqueous Ticarcillin Cloxacillin Penicillin G benzathine Ticarcillin-clavulanate Dicloxacillin Penicillin G procaine Tetracyclines Doxycycline Tetracycline Miscellaneous agents Aztreonam Linezolid Trimethoprim-sulfamethoxa- Clindamycin Meropenem zole (co-trimoxazole) Fosfomycin Metronidazole Vancomycin Imipenem-cilastatin Quinupristin/dalfopristin Antifungals Amphotericin B Clotrimazole and betametha- Miconazole Amphotericin B cholesteryl sone Nystatin Amphotericin B lipid com- Econazole Terbinafine plex Fluconazole Triamcinolone and nystatin Amphotericin B liposomal Itraconazole Clotrimazole Ketoconazole Antimycobacterials Clofazimine Isoniazid Rifampin Dapsone Pyrazinamide Rifapentine Ethambutol Rifabutin Antiretrovirals Abacavir Indinavir Saquinavir Amprenavir Lamivudine Stavudine Delavirdine Nelfinavir Zalcitabine Didanosine Nevirapine Zidovudine Efavirenz Ritonavir Zidovudine and lamivudine 22 478 Clinician’s Pocket Reference, 9th Edition Antivirals Acyclovir Ganciclovir Ribavirin Amantadine Interferon Alfa-2b and rib- Rimantadine Cidofovir avirin combination Valacyclovir Famciclovir Oseltamivir Zanamivir Foscarnet Penciclovir Miscellaneous Agents Atovaquone Pentamidine Trimetrexate Permethrin Antineoplastic Agents Alkylating Agents Altretamine Carboplatin Procarbazine Busulfan Cisplatin Triethylene-triphosphoramide Nitrogen Mustards Chlorambucil Ifosfamide Melphalan Cyclophosphamide Mechlorethamine Nitrosoureas Carmustine Lomustine Streptozocin Antibiotics Bleomycin sulfate Doxorubicin Pentostatin Dactinomycin Idarubicin Plicamycin Daunorubicin Mitomycin Valrubicin Antimetabolites Cytarabine Fludarabine Mercaptopurine Cytarabine liposomal Fluorouracil (5-FU) Methotrexate Floxuridine Gemcitabine 6-Thioguanine Hormones Anastrozole Flutamide Nilutamide Bicalutamide Goserelin Tamoxifen acetate Estramustine phosphate Leuprolide acetate Fluoxymesterone Megestrol acetate Mitotic Inhibitors Etoposide Vinblastine Vinorelbine Teniposide Vincristine Miscellaneous Agents Aldesleukin BCG (bacillus Calmette- Docetaxel Altretamine Guérin) Hydroxyurea Aminoglutethimide Cladribine Interferon Alfa 22 L-Asparaginase Dacarbazine Irinotecan 22 Commonly Used Medications 479 Letrozole Mitoxantrone Procarbazine Levcovorin Paclitaxel Topotecan Levamisole Pentostatin Tretinoin (retinoic acid) Mitotane Cardiovascular Agents α1-(Alpha) Blockers Doxazosin Prazosin Terazosin Angiotensin-converting Enzyme Inhibitors Benazepril Lisinopril Ramipril Captopril Moexipril Trandolapril Enalapril and enalaprilat Perindopril Fosinopril Quinapril Angiotensin II Receptor Antagonist Candesartan Irbesartan Telmisartan Eprosartan Losartan Valsartan Antiarrhythmic Agents Adenosine Esmolol Moricizine Amiodarone Flecainide Procainamide Atropine Ibutilide Propafenone Bretylium Lidocaine Quinidine Digoxin Methoxamine Sotalol Disopyramide Mexiletine Tocainide β-(Beta) Blockers Acebutolol Carteolol Penbutolol Atenolol Carvedilol Pindolol Atenolol and chlorthalidone Labetalol Propranolol Betaxolol Metoprolol Timolol Bisoprolol Nadolol Calcium Channel Antagonists Amlodipine Isradipine Nisoldipine Bepridil Nicardipine Verapamil Diltiazem Nifedipine Felodipine Nimodipine Centrally Acting Antihypertensive Agents Clonidine Guanadrel Guanfacine Guanabenz Guanethidine Methyldopa Diuretics Acetazolamide Ethacrynic acid Hydrochlorothiazide and Amiloride Furosemide spironolactone Bumetanide Hydrochlorothiazide Hydrochlorothiazide and tri- Chlorothiazide Hydrochlorothiazide and amterene Chlorthalidone amiloride Indapamide 22 480 Clinician’s Pocket Reference, 9th Edition Mannitol Spironolactone Triamterene Metolazone Torsemide Inotropic/Pressor Agents Amrinone Epinephrine Norepinephrine Digoxin Isoproterenol Phenylephrine Dobutamine Methoxamine Dopamine Milrinone Lipid-Lowering Agents Atorvastatin Colestipol Lovastatin Cerivastatin Fenofibrate Niacin Cholestyramine Fluvastatin Pravastatin Colesevelam Gemfibrozil Simvastatin Vasodilators Alprostadil Isosorbide dinitrate Nitroprusside Epoprostenol Isosorbide mononitrate Tolazoline Fenoldopam Minoxidil Hydralazine Nitroglycerin Central Nervous System Agents Antianxiety Alprazolam Diazepam Meprobamate Buspirone Doxepin Oxazepam Chlordiazepoxide Hydroxyzine Prazepam Clorazepate Lorazepam Anticonvulsants Carbamazepine Lamotrigine Phenytoin Clonazepam Levetiracetam Tiagabine Diazepam Lorazepam Topiramate Ethosuximide Oxcarbazepine Valproic acid Fosphenytoin Pentobarbital Zonisamide Gabapentin Phenobarbital Antidepressants Amitriptyline Fluvoxamine Phenelzine Amoxapine Imipramine Sertraline Bupropion Maprotiline Trazodone Citalopram Mirtazapine Trimipramine Desipramine Nefazodone Venlafaxine Doxepin Nortriptyline Fluoxetine Paroxetine Antiparkinson Agents Amantadine Entacapone Selegiline Benztropine Pergolide Trihexyphenidyl Bromocriptine Pramipexole 22 Carbidopa/levodopa Procyclidine 22 Commonly Used Medications 481 Antipsychotics Chlorpromazine Mesoridazine Quetiapine Clozapine Molindone Risperidone Fluphenazine Olanzapine Thioridazine Haloperidol Perphenazine Thiothixene Lithium carbonate Prochlorperazine Trifluoperazine Sedative Hypnotics Chloral hydrate Midazolam Secobarbital Diphenhydramine Pentobarbital Temazepam Estazolam Phenobarbital Triazolam Flurazepam Propofol Zaleplon Hydroxyzine Quazepam Zolpidem Miscellaneous Agents Nimodipine Rivastigmine Tacrine Dermatologic Agents Acitretin Clotrimazole and betametha- Nystatin Acyclovir sone Nystatin and triamcinolone Amphotericin B Dibucaine Oxiconazole Anthralin Doxepin Penciclovir Bacitracin Econazole Permethrin Bacitracin, topical Erythromycin, topical Pramoxine Bacitracin, neomycin and Finasteride Pramoxine and hydrocorti- polymyxin B, topical Gentamicin, topical sone Bacitracin, neomycin, Haloprogin Podophyllin polymyxin B and hydro- Imiquimod Selenium sulfide cortisone, topical Isotretinoin (13-cis retinoic Silver sulfadiazine Bacitracin, neomycin, acid) Steroids, topical (Table 22–6, polymyxin B and lido- Ketoconazole pages 628–630) caine, topical Lactic acid and ammonium Tazarotene Bacitracin and polymyxin B, hydroxide Terbinafine topical Lindane Tolnaftate Calcipotriene Metronidazole Tretinoin, topical (retinoic Capsaicin Miconazole acid) Ciclopirox Minoxidil Witch hazel Ciprofloxacin Mupirocin Clindamycin, topical Naftifine Dietary Supplements Calcium acetate Ferric gluconate complex Phytonadione (vitamin K) Calcium glubionate Ferrous gluconate Potassium supplements Calcium gluceptate Ferrous sulfate (Table 22–4, page 626) Calcium salts (chloride and Folic acid Pyridoxine (vitamin B6) gluconate) Iron dextran Sodium bicarbonate (bicar- Cholecalciferol Magnesium oxide bonate) Cyanocobalamin (vitamin B12) Magnesium sulfate Thiamine (vitamin B1) 22 482 Clinician’s Pocket Reference, 9th Edition Ear (Otic) Agents Acetic acid and aluminum ac- Neomycin, colistin, hydro- Sulfacetamide and pred- etate cortisone, and thonzo- nisolone Benzocaine and antipyrine nium Triethanolamine Ciprofloxacin and hydrocorti- Neomycin, polymyxin, and sone hydrocortisone Neomycin, colistin, and hy- Polymyxin B and hydrocorti- drocortisone sone Endocrine System Antidiabetic Agents Acarbose Glyburide Pioglitazone Acetohexamide Insulins (Table 22–2, page Repaglinide Chlorpropamide 622) Rosiglitazone Glimepiride Metformin Tolazamide Glipizide Miglitol Tolbutamide Hormone and Synthetic Substitutes Calcitonin Fludrocortisone acetate Prednisolone Calcitriol Glucagon Prednisone Cortisone Hydrocortisone Vasopressin Desmopressin Methylprednisolone Dexamethasone Metyrapone Hypercalcemia Agents Etidronate Pamidronate Gallium nitrate Plicamycin Obesity Sibutramine Osteoporosis Agents Alendronate Raloxifene Risedronate Thyroid/Antithyroid Levothyroxine Methimazole Liothyronine Propylthiouracil Miscellanous Agents Demeclocycline Diazoxide Metyrosine Eye (Ophthalmic) Agents Glaucoma Agents Acetazolamide Brinzolamide Dorzolamide and timolol Apraclonidine Carteolol Echothiophate iodine 22 Betaxolol Dipivefrin Latanoprost Brimonidine Dorzolamide Levobunolol 22 Commonly Used Medications 483 Levocabastine Metipranolol Lodoxamide Timolol Ophthalmic Antibiotics Bacitracin Gentamicin Sulfacetamide Bacitracin, neomycin and Neomycin and dexametha- Sulfacetamide and pred- polymyxin B sone nisolone Bacitracin, neomycin, Neomycin, polymyxin B and Tobramycin polymyxin B and hydro- dexamethasone Tobramycin and dexametha- cortisone Neomycin, polymyxin B and sone Bacitracin and polymyxin B prednisolone Trifluridine Ciprofloxacin Ofloxacin Erythromycin Silver nitrate Other Agents Artificial tears Dexamethasone (ophthalmic) Naphazoline and pheniramine Cromolyn Ketorolac Cyclopentolate Naphazoline and antazoline Gastrointestinal Agents Antacids Alginic acid Aluminum hydroxide with Aluminum hydroxide with Aluminum carbonate magnesium hydroxide magnesium trisilicate Aluminum hydroxide Aluminum hydroxide with Calcium carbonate Aluminum hydroxide with magnesium hydroxide and Magaldrate magnesium carbonate simethicone Simethicone Antidiarrheal Bismuth subsalicylate Lactobacillus Paregoric Diphenoxylate with atropine Loperamide Kaolin/pectin Octreotide Antiemetic Buclizine Droperidol Prochlorperazine Chlorpromazine Granisetron Promethazine Dimenhydrinate Meclizine Scopolamine Dolasetron Metoclopramide Thiethylperazine Dronabinol Ondansetron Trimethobenzamide Antiulcer Cimetidine Nizatidine Rabeprazole Famotidine Omeprazole Ranitidine Lansoprazole Pantoprazole Sucralfate Cathartics/Laxatives Bisacodyl Lactulose Polyethylene glycol-elec- Docusate calcium Magnesium citrate trolyte (PEG) solution Docusate potassium Magnesium hydroxide Psyllium Docusate sodium Mineral oil Sorbitol Glycerin suppositories 22 484 Clinician’s Pocket Reference, 9th Edition Enzymes Pancreatin Pancrelipase Miscellaneous Agents Alosetron Infliximab Propantheline Dexpanthenol Mesalamine Sulfasalazine Dibucaine Metoclopramide Vasopressin Dicyclomine Misoprostol Hydrocortisone, rectal Olsalazine Hyoscyamine Pramoxine Hyoscyamine, atropine, Pramoxine with hydrocorti- scopolamine, and pheno- sone barbital Hematologic Agents Anticoagulants Ardeparin Enoxaparin Protamine Dalteparin Heparin Warfarin Antiplatelet Agents Abciximab Eptifibatide Ticlopidine Aspirin Dipyridamole Tirofiban Clopidogrel Reteplase Antithrombic Agents Alteplase, recombinant (TPA) Aprotinin Streptokinase Aminocaproic acid Dextran 40 Tenecteplase Anistreplase Reteplase Urokinase Hemopoietic Stimulants Epoetin alfa (erythropoietin) Oprelvekin Filgrastim (G-CSF) Sargramostim (GM-CSF) Volume Expanders Albumin Hetastarch Dextran 40 Plasma protein fraction Miscellaneous Agents Antihemophilic factor VIII Lepirudin Desmopressin Pentoxifylline Immune System Agents Immunomodulators Interferon alfa Interferon beta-1b 22 Interferon alfacon-1 Interferon gamma-1b 22 Commonly Used Medications 485 Immunosuppressive Agents Antithymocyte globulin Cyclosporine Sirolimus (ATG) Dacliximab Steroids, systemic (See Table Azathioprine Muromonab-CD3 22–5, page 627 Basiliximab Mycophenolate mofetil Tacrolimus Vaccine/Serums/Toxoids CMV Immune globulin Immune globulin Pneumococcal 7-valent con- Haemophilus B conjugate Influenza vaccine jugate Hepatitis A vaccine Lyme disease vaccine Tetanus immune globulin Hepatitis B immune globulin Pneumococcal vaccine, poly- Tetanus toxoid Hepatitis B vaccine valent Varicella virus vaccine Musculoskeletal Agents Antigout Agents Allopurinol Probenecid Colchicine Sulfinpyrazone Muscle Relaxants Baclofen Cyclobenzaprine

Metaxalone Carisoprodol Dantrolene Methocarbamol Chlorzoxazone Diazepam Orphenadrine Neuromuscular Blockers Atracurium Pancuronium Succinylcholine Mivacurium Pipecuronium Vecuronium Miscellaneous Agents Edrophonium Leflunomide Methotrexate OB/GYN Agents Contraceptives Levonorgestrel implants Oral contraceptives biphasic Oral contraceptives progestin Oral contraceptives (Table 22–3, pages 623–625) only (Table 22–3, pages monophasic (Table 22–3, Oral contraceptives triphasic 623–625) pages 623–625) (Table 22–3, pages 623–625) Norgestrel Estrogen Supplementation Esterified estrogens Estradiol transdermal Estrogen, conjugated with Esterified estrogens with Estrogen, conjugated methyltestosterone methyltestosterone Estrogen, conjugated with Ethinyl estradiol Estradiol methylprogesterone Vaginal Preparations Amino-Cerv pH 5.5 cream Nystatin Tioconazole Miconazole Terconazole 22 486 Clinician’s Pocket Reference, 9th Edition Miscellaneous Agents Gonadorelin Medroxyprogesterone Oxytocin Leuprolide Methylergonovine Terbutaline Magnesium sulfate Mifepristone (RU486) Pain Relievers Local Anesthetics Benzocaine and antipyrine Cocaine Lidocaine and prilocaine Bupivacaine Dibucaine Pramoxine Capsaicin Lidocaine Migraine Headache Agents Acetaminophen with butal- Naratriptan bital ±/– caffeine Rizatriptan Aspirin with butalbital and Sumatriptan caffeine Zolmitriptan Narcotics Acetaminophen with codeine Hydrocodone and aspirin Oxycodone and aspirin Alfentanil Hydrocodone and ibuprofen Oxymorphone Aspirin with codeine Hydromorphone Pentazocine Buprenorphine Levorphanol Propoxyphene Butorphanol Meperidine Propoxyphene and aceta- Codeine Methadone minophen Dezocine Morphine Propoxyphene and aspirin Fentanyl Nalbuphine Sufentanil Fentanyl transdermal Oxycodone Fentanyl transmucosal Oxycodone and aceta- Hydrocodone and aceta- minophen minophen Nonnarcotic Agents Acetaminophen Tramadol Nonsteroidal Antiinflammatory Agents Aspirin Ibuprofen Naproxen sodium Celecoxib Indomethacin Oxaprozin Diclofenac Ketoprofen Piroxicam Diflunisal Ketorolac Rofecoxib Etodolac Meloxicam Sulindac Fenoprofen Nabumetone Tolmetin Flurbiprofen Naproxen Miscellanous Agents 22 Amitriptyline Imipramine Tramadol 22 Commonly Used Medications 487 Respiratory Agents Antitussives and Decongestants Acetylcysteine Guaifenesin and dex- ephedrine Benzonatate tromethorphan Hydrocodone, chlorpheni- Codeine Hydrocodone and guaifenesin ramine, phenylephrine, ac- Dextromethorphan Hydrocodone and homat- etaminophen, and caffeine Guaifenesin ropine Pseudoephedrine Guaifenesin and codeine Hydrocodone and pseudo- Bronchodilators Albuterol Epinephrine Pirbuterol Albuterol and ipratropium Isoetharine Salmeterol Aminophylline Isoproterenol Terbutaline Bitolterol Levalbuterol Theophylline Ephedrine Metaproterenol Respiratory Inhalants Acetylcysteine Colfosceril palmitate Fluticasone, oral, nasal Beclomethasone Cromolyn sodium Ipratropium Beractant Dexamethasone, nasal Nedocromil Calfactant Flunisolide Triamcinolone Miscellanous Agents Alpha1 protease inhibitor Montelukast Zileuton Dornase alfa Zafirlukast Urinary/Genitourinary Agents Alprostadil intracavernosal Hyoscyamine Phenazopyridine Alprostadil urethral supposi- Methenamine Potassium citrate tory Nalidixic acid Potassium citrate and citric Ammonium aluminum sul- Neomycin–polymyxin blad- acid fate (alum) der irrigant Sildenafil Belladonna and opium supp Nitrofurantoin Sodium citrate Bethanechol Oxybutynin Trimethoprim Dimethyl sulfoxide (DMSO) Pentosan polysulfate Tolterodine Flavoxate Benign Prostatic Hyperplasia Doxazosin Tamsulosin Finasteride Terazosin Wound Care Silver nitrate Becaplermin Miscellaneous Agents Megestrol acetate Nicotine gum Potassium iodide Metaraminol Nicotine nasal spray Sodium polystyrene sulfonate Naltrexone Nicotine transdermal Triethanolamine 22 488 Clinician’s Pocket Reference, 9th Edition GENERIC DRUG LISTING AND DATA Abacavir (Ziagen) COMMON USES: HIV infection ACTIONS: Nucleoside reverse transcriptase inhibitor DOSAGE: Adults. 300 mg bid. Peds. 8 mg/kg bid SUPPLIED: Tabs 300 mg; soln 20 mg/mL NOTES: Fatal hypersensitivity reactions possibly manifested as respiratory symptoms. Discontinue immediately if hypersensitivity symptoms arise (fever, skin rash, fatigue, nausea, vomiting, diar- rhea or abdominal pain). Lactic acidosis and hepatomegaly with steatosis also possible Abciximab (ReoPro) COMMON USES: Prevent acute ischemic complications in PTCA ACTIONS: Inhibits platelet aggregation (GPII b/IIIa inhibitor) DOSAGE: 0.25 mg/kg bolus 10–60 min prior to PTCA, then 0.125 µg/kg/min (max = 10 µg/min) cont inf for 12 h SUPPLIED: Inj 2 mg/mL NOTES: Used with heparin; allergic reactions possible Acarbose (Precose) COMMON USES: Type 2 DM ACTIONS: α-Glucosidase inhibitor; delays digestion of carbohydrates, resulting in lower plasma glucose levels DOSAGE: 25–100 mg PO tid at the start of each main meal SUPPLIED: Tabs 25, 50, 100 mg NOTES: May be taken with sulfonylureas Acebutolol (Sectral) COMMON USES: HTN ACTIONS: Competitively blocks β-adrenergic receptors, β1 and ISA DOSAGE: 200–800 mg/d SUPPLIED: Caps 200, 400 mg Acetaminophen (Tylenol, others) COMMON USES: Mild pain, headache, and fever ACTIONS: Nonnarcotic analgesic; inhibits synthesis of prostaglandins in the CNS and inhibits hy- pothalamic heat-regulating center DOSAGE: Adults. 650 mg PO or PR q4–6h or 1000 mg PO q6h; do not exceed 4 g/24h. Peds <12 y. 10–15 mg/kg/dose PO or PR q4–6h; do not exceed 2.6 g/24h. See quick dosing information in Table 22–1 (page 621). SUPPLIED: Tabs 160, 325, 500, 650 mg; chewable tabs 80, 160 mg; liq 100 mg/mL, 120 mg/2.5 mL, 120 mg/5 mL, 160 mg/5 mL, 167 mg/5 mL, 325 mg/5 mL, 500 mg/5 mL; gtt 48 mg/mL, 60 mg/0.6 mL; supp 80, 120, 125, 300, 325, 650 mg NOTES: No antiinflammatory or platelet-inhibiting action; ↓ dose with alcohol use; overdose causes hepatotoxicity, which is treated with N-acetylcysteine; charcoal not usually recommended Acetaminophen + Butalbital +/– Caffeine (Fioricet, Medigesic, Repan, Sedapap-10, Two-Dyne, Triapin, Axocet, Phrenilin Forte, others) [C-III] COMMON USES: Mild pain; headache, especially associated with stress ACTIONS: Nonnarcotic analgesic with barbiturate DOSAGE: 1–2 tabs or caps PO q4–6h PRN SUPPLIED: Caps Medigesic, Repan, Two-Dyne: Butalbital 50 mg, caffeine 40 mg, + acetaminophen 325 mg. Caps Axocet, Phrenilin Forte: Butalbital 50 mg and acetaminophen 650 mg; Triaprin: 22 Butalbital 50 mg + acetaminophen 325 mg. Tabs Esgic, Fioricet, Repan: Butalbital 50 mg, caffeine 22 Commonly Used Medications 489 40 mg, + acetaminophen 325 mg; Phrenilin: Butalbital 50 mg and acetaminophen 325 mg; Seda- pap-10: Butalbital 50 mg + acetaminophen 650 mg NOTES: Butalbital habit-forming Acetaminophen + Codeine (Tylenol No. 1, No. 2, No. 3, No. 4) [C-II] COMMON USES: No. 1, No. 2, and No. 3 for mild to moderate pain; No. 4 for moderate to severe pain ACTIONS: Combined effects of acetaminophen and a narcotic analgesic DOSAGE: Adults. 1–2 tabs q3–4h PRN. (Max dose acetaminophen = 4 g/d). Peds. Acetaminophen 10–15 mg/kg/dose; codeine 0.5–1.0 mg/kg dose q4–6h (useful dosing guide: 3–6 y, 5 mL/dose; 7–12 y, 10 mL/dose) SUPPLIED: Tabs 300 mg of APAP + codeine; caps 325 mg of APAP + codeine; liq acetaminophen 120 mg + codeine 12 mg/5 mL NOTES: Codeine in No. 1 = 7.5 mg, No. 2 = 15 mg, No. 3 = 30 mg, No.4 = 60 mg Acetazolamide (Diamox) COMMON USES: Diuresis, glaucoma, acute mountain sickness, and refractory epilepsy ACTIONS: Carbonic anhydrase inhibitor; ↓ renal excretion of hydrogen ions, and ↑ renal excretion of sodium, potassium, bicarbonate, and water DOSAGE: Adults. Diuretic: 250–375 mg IV or PO q24h. Glaucoma: 250–1000 mg PO q24h in ÷ doses. Epilepsy: 8–30 mg/kg/d PO in ÷ doses. Altitude sickness: 250 mg PO q8–12h or SR 500 mg PO q12–24h. Peds. Epilepsy: 8–30 mg/kg/24h PO in ÷ doses; max 1 g/d. Diuretic: 5 mg/kg/24h PO or IV. Alkalinization of urine: 5 mg/kg/dose PO bid–tid. Glaucoma: 5–15 mg/kg/24h PO in ÷ doses; max 1 g/d SUPPLIED: Tabs 125, 250 mg; SR caps 500 mg; inj 500 mg/vial NOTES: Contra in renal and hepatic failure, sulfa hypersensitivity; follow Na+ and K+; watch for metabolic acidosis; SR dosage forms not recommended for use in epilepsy Acetic Acid And Aluminum Acetate (Otic Domeboro) COMMON USES: Otitis externa ACTIONS: Antiinfective DOSAGE: 4–6 gtt in ear(s) q2–3h SUPPLIED: Otic soln Acetohexamide (Dymelor) COMMON USES: Type 2 DM ACTION: Sulfonylurea. Stimulates release of insulin from pancreas; increases insulin sensitivity at peripheral sites; reduces glucose output from liver DOSAGE: 250–1500 mg/d SUPPLIED: Tabs 250, 500 mg Acetylcysteine (Mucomyst, Mucosil) COMMON USES: Mucolytic agent as adjuvant Rx for chronic bronchopulmonary diseases and CF; antidote to acetaminophen hepatotoxicity within 24 h of ingestion ACTIONS: Splits disulfide linkages between mucoprotein molecular complexes; protects the liver by restoring glutathione levels in acetaminophen overdose DOSAGE: Adults & Peds. Nebulizer: 3–5 mL of 20% soln diluted with an equal vol of water or NS tid–qid. Antidote: PO or NG: 140 mg/kg loading dose, then 70 mg/kg q4h for 17 doses. Dilute 1:3 in carbonated beverage or orange juice SUPPLIED: Soln 10%, 20% NOTES: Watch for bronchospasm when used by inhalation in asthmatics; activated charcoal adsorbs acetylcysteine when given PO for acute APAP ingestion Acitretin (Soriatane) COMMON USES: Severe psoriasis and other keratinization disorders (lichen planus, etc) 22 490 Clinician’s Pocket Reference, 9th Edition ACTIONS: Retinoid-like activity DOSAGE: 25–50 mg/d PO, with main meal; can ↑ if no response by 4 wk to 75 mg/d SUPPLIED: Caps 10, 25 mg NOTES: Teratogenic, contra in PRG; Use with caution in women of reproductive potential; check LFTs, can be hepatotoxic; response often takes 2–3 mo Acyclovir (Zovirax) COMMON USES: Herpes simplex and herpes zoster viral infections ACTIONS: Interferes with viral DNA synthesis DOSAGE: Adults. Oral: Initial genital herpes: 200 mg PO q4h while awake, total of 5 caps/d for 10 d or 400 mg PO tid for 7–10 d. Chronic suppression: 400 mg PO bid. Intermittent Rx: As for initial treatment, except treat for 5 d, or 800 mg PO bid, initiated at the earliest prodrome. Herpes zoster: 800 mg PO 5×/d for 7–10 d. IV. 5–10 mg/kg/dose IV q8h. Topical initial herpes genitalis: Apply q3h (6×/d) for 7 d. Peds. 5–10 mg/kg/dose IV or PO q8h or 750 mg/m2/24h ÷ q8h. Chickenpox: 20 mg/kg/dose PO qid SUPPLIED: Caps 200 mg; tabs 400, 800 mg; susp 200 mg/5 mL; inj 500 mg/vial; oint 5% NOTES: Adjust dose in renal insufficiency; oral better than topical for herpes genitalis Adenosine (Adenocard) Used for emergency cardiac care (see Chapter 21). COMMON USES: PSVT, including that associated with Wolff-Parkinson-White syndrome ACTIONS: Class IV antiarrhythmic; slows conduction time through the AV node DOSAGE: Adults. 6 mg rapid IV bolus; may be repeated in 1–2 min; max 12 mg IV. Peds. 0.05 mg/kg IV bolus; may repeat q 1–2 min to a max of 0.25 mg/kg SUPPLIED: Inj 6 mg/2 mL NOTES: Doses >12 mg not recommended; caffeine and theophylline antagonize effects of adeno- sine Albumin (Albuminar, Buminate, Albutein, others) COMMON USES: Plasma volume expansion for shock resulting from burns, surgery, hemorrhage, or other trauma ACTIONS: Maintenance of plasma colloid oncotic pressure DOSAGE: Adults. Initially, 25 g IV; subsequent infusions depend on clinical situation and response. No more than 250 g/48h. Peds. 0.5–1.0 g/kg/dose; infuse at 0.05–0.1 g/min SUPPLIED: Soln 5%, 25% NOTES: Contains 130–160 meq Na+/L. Albuterol (Proventil, Ventolin) COMMON USES: Bronchospasm in reversible obstructive airway disease; prevention of exercise- induced bronchospasm ACTIONS: β-Adrenergic sympathomimetic bronchodilator; relaxes bronchial smooth muscle DOSAGE: Adults. 2 inhal q4–6h PRN; 1 Rotacaps inhaled q4–6h; 2–4 mg PO tid–qid; Neb: 1.25– 5 mg (0.25–1 mL of 0.5% soln) in 2–3 mL of NS tid–qid. Peds. 2 inhal q4–6h; 0.1–0.2 mg/kg/dose PO; max 2–4 mg PO tid; Neb: 0.05 mg/kg (max 2.5 mg) in a 2–3 mL of NS tid–qid SUPPLIED: Tabs 2, 4 mg; ER tabs 4, 8 mg; syrup 2 mg/5 mL; 90 µg/dose met-dose inhaler; Rota- caps 200 µg; soln for neb 0.083, 0.5% Albuterol and Ipratropium (Combivent) COMMON USES: COPD ACTIONS: Combination of β-adrenergic bronchodilator and quaternary anticholinergic compound DOSAGE: 2 inhal qid 22 SUPPLIED: Met-dose inhaler, 18 µg ipratropium/103 µg Albuterol/puff 22 Commonly Used Medications 491 Aldesleukin [IL-2] (Proleukin) COMMON USES: RCC, melanoma ACTIONS: Acts via IL-2 receptor; numerous immunomodulatory effects DOSAGE: 600,000 IU/kg q8h for 14 doses (FDA-approved dose/schedule for RCC). Multiple cont inf and SCSC dosing schedules (including “high-dose” therapy with 24 × 106 IU/m2 IV q8h on d 1–5 and 12–16) SUPPLIED: Inj 1.1 mg/mL (22 × 106 IU) NOTES: Toxicity symptoms: flu-like syndrome (malaise, fever, chills), nausea and vomiting, diar- rhea, and increased serum bilirubin. Capillary leak syndrome with hypotension, pulmonary edema, fluid retention, and weight gain. Renal toxicity and mild hematologic toxicity (anemia, thrombocy- topenia, leukopenia) and secondary eosinophilia. Cardiac toxicity (myocardial ischemia, atrial ar- rhythmias). Neurologic toxicity (CNS depression, somnolence, rarely coma, delirium). Pruritic skin rashes, urticaria, and erythroderma common. Cont inf schedules less likely in severe hypoten- sion and fluid retention Alendronate (Fosamax) COMMON USES: Rx and prevention of osteoporosis, Rx of glucocorticoid-induced osteoporosis and Paget’s disease ACTIONS: Inhibits normal and abnormal bone resorption DOSAGE: Osteoporosis: Rx: 10 mg/d PO. Glucocorticoid-induced osteoporosis: Rx: 5 mg/d PO. Prevention: 5 mg/d PO. Paget’s disease: 40 mg/d PO SUPPLIED: Tabs 5, 10, 40 mg NOTES: Take first thing in AM with plain water (8 oz) at least 30 min prior to the first food or bever- age of the day. Do not lie down for 30 min after taking. Adequate calcium and vitamin D supple- ment necessary Alfentanil (Alfenta) [C] COMMON USES: Adjunct in the maintenance of anesthesia; analgesia ACTIONS: Short-acting narcotic analgesic DOSAGE: Adults & Peds >12 y. 3–75 µg/kg IV inf; total dose depends on duration of procedure SUPPLIED: Inj 500 µg/mL Alginic Acid + Aluminum Hydroxide and Magnesium Trisilicate (Gaviscon) COMMON USES: Heartburn; pain from hiatal hernia ACTIONS: Forms protective layer preventing reflux of gastric acid DOSAGE: 2–4 tabs or 15–30 mL PO qid followed by

water SUPPLIED: Tabs, susp Allopurinol (Zyloprim, Lopurin, Aloprim, others) COMMON USES: Gout, hyperuricemia of malignancy, and uric acid urolithiasis ACTIONS: Xanthine oxidase inhibitor, which decreases the production of uric acid DOSAGE: Adults. PO: Initially, 100 mg/d; usual 300 mg/d; max 800 mg/d. IV: 200–400 mg/m2/d (max 600 mg/24h). Peds. Use only for treating hyperuricemia of malignancy in children (<10 y): 10 mg/kg/24h PO or 200 mg/m2/d IV ÷ q6–8h (max 600 mg/24h) SUPPLIED: Tabs 100, 300 mg; inj 500 mg/30 mL NOTES: Aggravates acute gouty attack; do not begin until acute attack resolves; administer pc. IV administration of 6 mg/mL final conc as single daily infusion or ÷ 6-, 8-, or 12-h intervals. Dosage adjustment necessary in renal impairment Alosetron (lotronex) COMMON USES: Irritable bowel syndrome in women, diarrhea as main symptom ACTIONS: 5-HT3 receptor antagonist NOTES: Removed from the market 22 492 Clinician’s Pocket Reference, 9th Edition α(-Protease Inhibitor (Prolastin) COMMON USES: Panacinar emphysema ACTIONS: Replacement of human α1-protease inhibitor DOSAGE: 60 mg/kg IV once/wk SUPPLIED: Inj 500 mg/20 mL; 1000 mg/40 mL Alprazolam (Xanax) [C] COMMON USES: Anxiety and panic disorders + anxiety associated with depression ACTIONS: Benzodiazepine; antianxiety agent DOSAGE: Anxiety: Initially, 0.25–0.5 mg tid; ↑ to a max of 4 mg/d in ÷ doses. Panic: Initially, 0.5 mg tid; may gradually ↑ to desired response SUPPLIED: Tabs 0.25, 0.5, 1.0, 2.0 mg NOTES: ↓ Dose in elderly and debilitated patients; avoid abrupt discontinuation after prolonged use Alprostadil, Intracavernosal (Caverject, Edex) COMMON USES: Erectile dysfunction due to neurogenic, vasculogenic, or mixed cause ACTIONS: Relaxes smooth muscles, dilates cavernosal arteries, increases lacunar spaces and entrap- ment of blood by compressing venules against tunica albuginea DOSAGE: 2.5–60 µg intracavernosal; adjusted to individual needs SUPPLIED: Caverject: 6–10 or 6–20 µg vials +/– diluent syringes. Edex: 5, 10, 20, 40 µg vials + syringes NOTES: Penile pain common side effect; dosage must be titrated at physician’s office. Patients should be informed of other side effects, including priapism, penile fibrosis, and hematoma Alprostadil [Prostaglandin E1] (Prostin VR) COMMON USES: Any state in which blood flow must be maintained through the ductus arteriosus to sustain either pulmonary or systemic circulation until corrective or palliative surgery can be per- formed (eg, pulmonary atresia, pulmonary stenosis, tricuspid atresia, transposition, severe tetralogy of Fallot) ACTIONS: Vasodilator, platelet aggregation inhibitor. Smooth muscle of the ductus arteriosus is es- pecially sensitive DOSAGE: 0.05 µg/kg/min IV. ↓ Dosage to lowest rate that maintains response SUPPLIED: Injectable forms NOTES: Cutaneous vasodilation, seizure-like activity, jitteriness, temperature elevation, hypocal- cemia, apnea, thrombocytopenia, hypotension. May cause apnea. Have an intubation kit at bedside if patient is not intubated Alprostadil, Urethral Suppository (Muse) COMMON USES: Erectile dysfunction ACTIONS: Alprostadil (PGE1) absorbed through urethral mucosa. Portion of administered dose transported to the corpus cavernosa where it acts as vasodilator and smooth muscle relaxant DOSAGE: 125–1000 µg system 5–10 min prior to sexual activity SUPPLIED: 125, 250, 500, 1000 µg with a transurethral delivery system NOTES: Hypotension, dizziness, syncope, penile pain, and priapism. Dose titration administered under physician’s supervision Alteplase, Recombinant [TPA] (Activase) Used for emergency cardiac care (see Chapter 21) COMMON USES: AMI, PE, and acute ischemic stroke ACTIONS: Results in thrombolysis; inhibits local fibrinolysis by binding to fibrin in the thrombus DOSAGE: AMI and PE: 100 mg IV over 3 h (10 mg over 2 min, then 50 mg over 1 h, then 40 mg over 2 h). Stroke: 0.9 mg/kg (max 90 mg) infused over 60 min 22 SUPPLIED: Powder for inj 50, 100 mg 22 Commonly Used Medications 493 NOTES: May cause bleeding; give heparin to prevent reocclusion. In AMI doses of >150 mg associ- ated with intracranial bleeding Altretamine (Hexalen) COMMON USES: Epithelial ovarian cancer ACTIONS: Unknown; cytotoxic agent, possibly alkylating agent; inhibits nucleotide incorporation into DNA and RNA DOSAGE: 260 mg/m2/d in 4 ÷ doses for 14–21 d of a 28-d treatment cycle; dose ↓ to 150 mg/m2/d for 14 d in multiagent regimens. (Refer to specific protocols) SUPPLIED: Caps 50, 100 mg NOTES: Toxicity symptoms: Vomiting, diarrhea, and cramps; neurologic toxicity (peripheral neu- ropathy, CNS depression); minimally myelosuppressive Aluminum Carbonate (Basaljel) COMMON USES: Hyperacidity (peptic ulcer, GERD, etc); supplement to the Rx of hyperphos- phatemia ACTIONS: Neutralizes gastric acid; binds phosphate DOSAGE: Adults. 2 caps or tabs or 10 mL (in water) q2h PRN. Peds. 50–150 mg/kg/24h PO ÷ q4–6h SUPPLIED: Tabs, caps, susp Aluminum Hydroxide (Amphojel, Alternagel) COMMON USES: Hyperacidity (peptic ulcer, hiatal hernia, etc); supplement to Rx of hyperphos- phatemia ACTIONS: Neutralizes gastric acid; binds phosphate DOSAGE: Adults. 10–30 mL or 2 tabs PO q4–6h. Peds. 5–15 mL PO q4–6h or 50–150 mg/kg/24h PO ÷ q4–6h (hyperphosphatemia) SUPPLIED: Tabs 300, 600 mg; chewable tabs 500 mg; susp 320, 600 mg/5 mL NOTES: Can be used in renal failure; may cause constipation Aluminum Hydroxide + Magnesium Carbonate (Gaviscon) COMMON USES: Hyperacidity (peptic ulcer, hiatal hernia, etc) ACTIONS: Neutralizes gastric acid DOSAGE: Adults. 15–30 PO pc and hs. Peds. 5–15 mL PO qid or PRN SUPPLIED: Liq containing aluminum hydroxide 95 mg + magnesium carbonate 358 mg/15 mL NOTES: Doses qid are best given pc and hs; may cause hypermagnesemia Aluminum Hydroxide + Magnesium Trisilicate (Gaviscon, Gaviscon-2) COMMON USES: Hyperacidity ACTIONS: Neutralizes gastric acid DOSAGE: Chew 2–4 tabs qid SUPPLIED: Gaviscon: Aluminum hydroxide 80 mg and magnesium trisilicate 20 mg; Gaviscon 2: Aluminum hydroxide 160 mg and magnesium trisilicate 40 mg Aluminum Hydroxide + Magnesium Hydroxide (Maalox) COMMON USES: Hyperacidity (peptic ulcer, hiatal hernia, etc) ACTIONS: Neutralizes gastric acid DOSAGE: Adults. 10–60 mL or 2–4 tabs PO qid or PRN. Peds. 5–15 mL PO qid or PRN SUPPLIED: Tabs, susp NOTES: Doses qid best given pc and hs; may cause hypermagnesemia in renal insufficiency Aluminum Hydroxide + Magnesium Hydroxide and Simethicone (Mylanta, Mylanta II, Maalox Plus) COMMON USES: Hyperacidity with bloating 22 494 Clinician’s Pocket Reference, 9th Edition ACTIONS: Neutralizes gastric acid DOSAGE: Adults. 10–60 mL or 2–4 tabs PO qid or PRN. Peds. 5–15 mL PO qid or PRN SUPPLIED: Tabs, susp NOTES: May cause hypermagnesemia in renal insufficiency; Mylanta II contains twice the alu- minum and magnesium hydroxide of Mylanta Amantadine (Symmetrel) COMMON USES: Rx or prophylaxis for influenza A viral infections and Parkinsonism ACTIONS: Prevents release of infectious viral nucleic acid into the host cell; releases dopamine from intact dopaminergic terminals DOSAGE: Adults. Influenza A: 200 mg/d PO or 100 mg PO bid. Parkinsonism: 100 mg PO qd–bid. Peds. 1–9 y: 4.4–8.8 mg/kg/24h to a max of 150 mg/24h ÷ doses qd–bid. 10–12 y: 100–200 mg/d in 1–2 ÷ doses SUPPLIED: Caps 100 mg; tabs 100 mg, soln 50 mg/5 mL NOTES: ↓ in renal insufficiency Amifostine (Ethyol) COMMON USES: Xerostomia prophylaxis during radiation therapy for head and neck, ovarian, or non-small-cell lung cancer. Reduction of cumulative renal toxicity associated with repeated admin- istration of cisplatin ACTIONS: Prodrug, dephosphorylated by alkaline phosphatase to the pharmacologically active thiol metabolite DOSAGE: 910 mg/m2/d as a 15-min IV inf 30 min prior to chemotherapy SUPPLIED: Vials containing 500 mg of lyophilized drug with 500 mg of mannitol, reconstituted in sterile NS NOTES: Toxicity symptoms: Transient hypotension in >60%, nausea and vomiting, flushing with hot or cold chills, dizziness, hypocalcemia, somnolence, and sneezing. Does not reduce the effective- ness of cyclophosphamide plus cisplatin chemotherapy Amikacin (Amikin) COMMON USES: Serious infections caused by gram (−) bacteria and mycobacterial infections ACTIONS: Aminoglycoside antibiotic; inhibits protein synthesis DOSAGE: See also page 620. Adults & Peds. 5–7.5 mg/kg/dose ÷ q8–24h based on renal function. Neonates. <1200 g, 0–4 wk: 7.5 mg/kg/dose q12h-18h. Postnatal age <7 d. 1200–2000 g: 7.5 mg/kg/dose q12h. >2000 g: 10 mg/kg/dose q12h. Postnatal age >7 d. 1200–2000 g: 7 mg/kg/dose q8h. >2000 g: 7.5–10 mg/kg/dose q8h SUPPLIED: Inj 100, 500 mg/2 mL NOTES: May be effective against gram (−) bacteria resistant to gentamicin and tobramycin; monitor renal function carefully for dosage adjustments; monitor serum levels (see Table 22–7, pages 631–634) Amiloride (Midamor) COMMON USES: HTN and CHF ACTIONS: K+-sparing diuretic; interferes with K+/Na+ exchange in the distal tubules DOSAGE: Adults. 5–10 mg PO qd. Peds. 0.625 mg/kg/d SUPPLIED: Tabs 5 mg NOTES: Hyperkalemia possible; monitor serum K+ levels Aminocaproic Acid (Amicar) COMMON USES: Excessive bleeding resulting from systemic hyperfibrinolysis and urinary fibrinol- ysis ACTIONS: Inhibits fibrinolysis via inhibition of TPA substances DOSAGE: Adults. 5 g IV or PO (1st h) followed by 1–1.25 g/h IV or PO. Peds. 100 mg/kg IV (1st h), (Max dose/d: 30 g), then 1 g/m2/h; max 18 g/m2/d 22 SUPPLIED: Tabs 500 mg; syrup 250 mg/mL; inj 250 mg/mL 22 Commonly Used Medications 495 NOTES: Administer for 8 h or until bleeding is controlled; contra in DIC; not for upper urinary tract bleeding Amino-Cerv pH 5.5 Cream COMMON USES: Mild cervicitis, postpartum cervicitis/cervical tears, postcauterization, post- cryosurgery, and postconization DOSAGE: 1 applicator full intravaginally hs for 2–4 wk SUPPLIED: Vaginal cream NOTES: Contains 8.34% urea, 0.5% sodium propionate, 0.83% methionine, 0.35% cystine, 0.83% inositol, and benzalkonium chloride Aminoglutethimide (Cytadren) COMMON USES: Adrenal cortex carcinoma, Cushing’s syndrome, breast cancer, and prostate cancer ACTIONS: Inhibits adrenal steroidogenesis and adrenal conversion of androgens to estrogens DOSAGE: 750–1500 mg/d in ÷ doses plus hydrocortisone 20–40 mg/d SUPPLIED: Tabs 250 mg NOTES: Toxicity symptoms: Adrenal insufficiency (“medical adrenalectomy”), hypothyroidism, masculinization, hypotension, vomiting, rare hepatotoxicity, rash, myalgia, and fever Aminophylline Used for emergency care (see Chapter 21) COMMON USES: Asthma and bronchospasm ACTIONS: Relaxes the smooth muscle of the bronchi and pulmonary blood vessels DOSAGE: Adults. Acute asthma: Load 6 mg/kg IV, then 0.4–0.9 mg/kg/h IV cont inf. Chronic asthma: 24 mg/kg/24h PO or PR ÷ q6h. Peds. Load 6 mg/kg IV, then 1.0 mg/kg/h IV cont inf SUPPLIED: Tabs 100, 200 mg; soln 105 mg/5 mL; supp 250, 500 mg; inj 25 mg/mL NOTES: Individualize dosage. Toxicity symptoms: Nausea and vomiting, irritability, tachycardia, ventricular arrhythmias, and seizures; follow serum levels carefully (as theophylline, see Table 22–7, pages 631–634); aminophylline is about 85% theophylline; erratic absorption with rectal doses Amiodarone (Cordarone) (Pacerone) COMMON USES: Recurrent VF or hemodynamically unstable VT ACTIONS: Class III antiarrhythmic DOSAGE: Adults. Loading dose: 800–1600 mg/d PO for 1–3 wk. Maintenance: 600–800 mg/d PO for 1 mo, then 200–400 mg/d IV: 15 mg/min for 10 min, followed by 1 mg/min for 6 h, then a maintenance dose of 0.5 mg/min cont inf. Peds. 10–15 mg/kg/24h ÷ q12h PO for 7–10 d, then 5 mg/kg/24h ÷ q12h or qd (infants and neonates may require a higher loading dose) SUPPLIED: Tabs 200 mg; inj 50 mg/mL NOTES: Average half-life is 53 d; potentially toxic effects leading to pulmonary fibrosis, liver fail- ure, and ocular opacities, as well as exacerbation of arrhythmias; IV concentrations of 0.2 mg/mL administered via a central catheter Amitriptyline (Elavil, others) COMMON USES: Depression, peripheral neuropathy, chronic pain, and cluster and migraine headaches ACTIONS: Tricyclic antidepressant; inhibits reuptake of serotonin and norepinephrine by the pre- synaptic neuronal membrane DOSAGE: Adults. Initially, 30–50 mg PO hs; may ↑ to 300 mg hs. Peds. Not recommended for chil- dren <12 y unless for chronic pain; initially, 0.1 mg/kg PO hs, then advance over 2–3 wk to 0.5–2 mg/kg PO hs SUPPLIED: Tabs 10, 25, 50, 75, 100, 150 mg; inj 10 mg/mL NOTES: Strong anticholinergic side effects; may cause urine retention and sedation; overdose may be fatal 22 496 Clinician’s Pocket Reference, 9th Edition Amlodipine (Norvasc) COMMON USES: HTN, chronic stable angina, and vasospastic angina ACTIONS: Calcium channel-blocking agent; produces relaxation of coronary vascular smooth muscle DOSAGE: 2.5–10 mg/d PO SUPPLIED: Tabs 2.5, 5, 10 mg NOTES: May be taken without regard to meals Ammonium Aluminum Sulfate (Alum) COMMON USES: Hemorrhagic cystitis when bladder irrigation fails ACTIONS: Astringent DOSAGE: 1–2% soln used with constant bladder irrigation with NS SUPPLIED: Powder for reconstitution NOTES: Can be used safely without anesthesia and in the presence of vesicoureteral reflux. En- cephalopathy possible; obtain aluminum levels, especially in renal insufficiency. Alum soln often precipitates and occludes catheters Amoxapine (Asendin) COMMON USES: Depression and anxiety ACTIONS: Tricyclic antidepressant; reduces reuptake of serotonin and norepinephrine DOSAGE: Initially, 150 mg PO hs or 50 mg PO tid; ↑ to 300 mg/d SUPPLIED: Tabs 25, 50, 100, 150 mg NOTES: ↓ in elderly; taper slowly when discontinuing therapy Amoxicillin (Amoxil, Polymox, others) COMMON USES: Infections resulting from susceptible gram (+) bacteria (streptococci) and gram (−) bacteria (H. influenzae, E. coli, P. mirabilis) ACTIONS: β-Lactam

antibiotic; inhibits cell wall synthesis DOSAGE: Adults. 250–500 mg PO tid or 500–875 mg bid. Peds. 25–100 mg/kg/24h PO ÷ q8h. 200–400 mg PO bid (equivalent to 125–250 mg tid) SUPPLIED: Caps 250, 500 mg; chewable tabs 125, 200, 250, 400 mg; susp 50 mg/mL, 125, 250 mg/5mL; tabs 500, 875 mg NOTES: Cross-hypersensitivity with penicillin; may cause diarrhea; skin rash common; many hos- pital strains of E. coli resistant Amoxicillin and Clavulanic Acid (Augmentin) COMMON USES: Infections caused by β-lactamase-producing strains of H. influenzae, S. aureus, and E. coli ACTIONS: Combination of a β-lactam antibiotic and a β-lactamase inhibitor DOSAGE: Adults. 250–500 mg PO q8h or 875 mg q12h. Peds. 20–40 mg/kg/d as amoxicillin PO ÷ q8h or 45 mg/kg/d ÷ q12h SUPPLIED: (Expressed as amoxicillin/clavulanic acid) Tabs 250/125, 500/125, 875/125 mg; chew- able tabs 125/31.25, 200/28.5, 250/62.5, 400/57 mg; susp 125/31.25, 250/62.5, 200/28.5, 400/57 mg/5 mL NOTES: Do not substitute two 250-mg tabs for one 500-mg tab or an overdose of clavulanic acid will occur; may cause diarrhea and GI intolerance Amphotericin B (Fungizone) COMMON USES: Severe, systemic fungal infections; oral and cutaneous candidiasis ACTIONS: Binds to ergosterol in the fungal membrane, altering membrane permeability DOSAGE: Adults & Peds. Test dose of 1 mg in adults or 0.1 mg/kg to 1 mg in children, then 0.25–1.5 mg/kg/24h IV over 2–6 h. Doses often range from 25 to 50 mg/d or every other day. Total dose varies with indication. Oral: 1 mL qid. Topical: Apply bid–qid for 1–4 wk depending on in- 22 fection 22 Commonly Used Medications 497 SUPPLIED: Powder for inj 50 mg/vial, oral susp 100 mg/mL, cream, lotion, oint 3% NOTES: Monitor renal function; hypokalemia and hypomagnesemia possible from renal wasting; pretreatment with acetaminophen and antihistamines (Benadryl) help minimize adverse effects as- sociated with IV infusion Amphotericin B Cholesteryl (Amphotec) COMMON USES: Refractory invasive fungal infection in persons intolerant to conventional ampho- tericin B ACTIONS: Binds to sterols in the cell membrane, resulting in changes in membrane permeability DOSAGE: Adults & Peds. Test dose of 1.6–8.3 mg, over 15–20 min, followed by a dose of 3–4 mg/kg/d. Infuse at a rate of 1 mg/kg/h SUPPLIED: Powder for inj 50 mg, 100 mg/vial NOTES: Do NOT use in-line filter, final concentration 0.6 mg/mL Amphotericin B Lipid Complex (Abelcet) COMMON USES: Refractory invasive fungal infection in persons intolerant to conventional ampho- tericin B ACTIONS: Binds to sterols in the cell membrane, resulting in changes in membrane permeability DOSAGE: 5 mg/kg/d IV administered as a single daily dose; infuse at a rate of 2.5 mg/kg/h SUPPLIED: Inj 5 mg/mL NOTES: Filter soln with a 5-mm filter needle; do not mix in electrolyte-containing solns. If inf >2 h, manually mix contents of the bag Amphotericin B Liposomal (Ambisome) COMMON USES: Refractory invasive fungal infection in persons intolerant to conventional ampho- tericin B ACTIONS: Binds to sterols in the cell membrane, resulting in changes in membrane permeability DOSAGE: Adults & Peds. 3–5 mg/kg/d, infused over 60–120 min SUPPLIED: Powder for inj 50 mg Ampicillin (Amcil, Omnipen, others) COMMON USES: Susceptible gram (−) (Shigella, Salmonella, E. coli, H. influenzae, and P. mirabilis) and gram (+) (streptococci) bacteria ACTIONS: β-Lactam antibiotic; inhibits cell wall synthesis DOSAGE: Adults. 500 mg to 2 g IM or IV q6h or 250–500 mg PO q6h. Peds. Neonates <7 d: 50–100 mg/kg/24h IV ÷ q8h. Term infants: 75–150 mg/kg/24h ÷ q6–8h IV or PO. Children >1 mo: 100–200 mg/kg/24h ÷ q4–6h IM or IV; 50–100 mg/kg/24h ÷ q6h PO up to 250 mg/dose. Meningi- tis: 200–400 mg/kg/24h ÷ q4–6h IV SUPPLIED: Caps 250, 500 mg; susp 100 mg/mL (reconstituted as drops), 125 mg/5 mL, 250 mg/ 5 mL, 500 mg/5 mL; powder for inj 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g/vial NOTES: Cross-hypersensitivity with penicillin; can cause diarrhea and skin rash; many hospital strains of E. coli now resistant Ampicillin-Sulbactam (Unasyn) COMMON USES: Infections caused by β-lactamase-producing strains of S. aureus, Enterococcus, H. influenzae, P. mirabilis, and Bacteroides spp ACTIONS: Combination of a β-lactam antibiotic and a β-lactamase inhibitor DOSAGE: Adults. 1.5–3.0 g IM or IV q6h. Peds. 100–200 mg ampicillin/kg/d (150–300 mg Unasyn) q6h SUPPLIED: Powder for inj 1.5, 3.0 g/vial NOTES: 2:1 ratio of ampicillin: Sulbactam; adjust dose in renal failure; observe for hypersensitivity reactions 22 498 Clinician’s Pocket Reference, 9th Edition Amprenavir (Agenerase) COMMON USES: HIV infection ACTIONS: Protease inhibitor, prevents the maturation of the virion to a mature viral particle DOSAGE: Adults. 1200 mg bid. Peds. 20 mg/kg bid or 15 mg/kg tid up to 2400 mg/d SUPPLIED: Caps 50, 150 mg; soln 15 mg/mL NOTES: Caps and soln contain vitamin E exceeding the reference daily intake amounts; avoid high- fat meals with administration; many drug interactions; life-threatening rash, hyperglycemia, and fat redistribution possible; use with caution in persons with known sulfa allergy Amrinone (Inocor) Used for emergency cardiac care (see Chapter 21) COMMON USES: Short-term Rx low cardiac output states and pulmonary HTN ACTIONS: Positive inotrope with vasodilator activity DOSAGE: Adults & Peds. Initially, give IV bolus of 0.75 mg/kg over 2–3 min followed by a mainte- nance dose of 5–10 µg/kg/min SUPPLIED: Inj 5 mg/mL NOTES: Not to exceed 10 mg/kg/d; incompatible with dextrose-containing solns; monitor for fluid and electrolyte changes and renal function during therapy Anastrozole (Arimidex) COMMON USES: Breast cancer following tamoxifen ACTIONS: Selective nonsteroidal aromatase inhibitor, ↓ circulating estradiol DOSAGE: 1 mg/d SUPPLIED: Tabs 1 mg NOTES: No detectable effect on adrenal corticosteroids or aldosterone; may ↑ cholesterol levels Anistreplase (Eminase) Used for emergency cardiac care (see Chapter 21) COMMON USES: AMI ACTIONS: Thrombolytic agent; activates the conversion of plasminogen to plasmin, promoting thrombolysis DOSAGE: 30 U IV over 2–5 min SUPPLIED: Vials containing 30 U NOTES: May not be effective if readministered >5 d after the previous dose of anistreplase, strep- tokinase, or streptococcal infection because of the production of antistreptokinase antibody Anthralin (Anthraderm, others) COMMON USES: Psoriasis ACTIONS: Keratolytic DOSAGE: Apply qd SUPPLIED: Cream, oint 0.1; 0.2 ; 0.25; 0.4; 0.5; 1% Antihemophilic Factor [Factor VIII] [AHF] (Monoclate) COMMON USES: Classic hemophilia A ACTIONS: Provides factor VIII needed to convert prothrombin to thrombin DOSAGE: Adults & Peds. 1 AHF unit/kg increases factor VIII conc in the body by approximately 2%. Units required = (kg) (desired factor VIII ↑ as % normal) × (0.5). Prophylaxis of spontaneous hemorrhage = 5% normal. Hemostasis following trauma or surgery = 30% normal. Head injuries, major surgery, or bleeding = 80–100% normal. Patient’s % of normal level of factor VIII concen- tration must be ascertained prior to dosing for these calculations SUPPLIED: Check each vial for number of units contained 22 NOTES: Not effective in controlling bleeding in von Willebrand’s disease 22 Commonly Used Medications 499 Antithymocyte Globulin [ATG] (Atgam) COMMON USES: Allograft rejection in transplant patients ACTIONS: Reduces the number of circulating, thymus-dependent lymphocytes DOSAGE: Adults & Peds. 10–15 mg/kg/d SUPPLIED: Inj 50 mg/mL NOTES: Do not administer in cases of prior history of severe systemic reaction to any other equine γ-globulin preparation; discontinue treatment with severe thrombocytopenia or leukopenia Apraclonidine (Iodipine) COMMON USES: Glaucoma ACTIONS: α2-Adrenergic agonist DOSAGE: 1–2 gtt of 0.5% tid SUPPLIED: 0.5, 1.0% soln Aprotinin (Trasylol) COMMON USES: Reduction or prevention of blood loss in patients undergoing a CABG ACTIONS: Protease inhibitor; antifibrinolytic DOSAGE: High-dose: 2 million KIU load, 2 million KIU for the pump prime dose, followed by 500,000 KIU/h until surgery ends. Low-dose: 1 million KIU load, 1 million KIU for the pump prime dose, followed by 250,000 KIU/h until surgery ends. Max total dose of 7 million KIU SUPPLIED: Inj 1.4 mg/mL (10,000 KIU/mL) NOTES: 1000/KIU = 0.14 mg of aprotinin. Give all patients 1-mL IV test dose to assess for allergic reaction Ardeparin (Normiflo) COMMON USES: Prevention of DVT and PE following knee replacement ACTIONS: Low-molecular-weight heparin DOSAGE: 35–50 U/kg SC q12h. Begin the day of surgery and continue up to 14 d SUPPLIED: Inj 5000, 10,000 IU/0.5 mL NOTES: Laboratory monitoring not necessary Artificial Tears (Tears Naturale, others) COMMON USES: Dry eyes ACTIONS: Ocular lubricant DOSAGE: 1–2 gtt tid–qid SUPPLIED: OTC soln L-Asparaginase (Elspar) COMMON USES: ALL (in combination with other agents) ACTIONS: Protein synthesis inhibitor DOSAGE: 500–20,000 IU/m2/d for 1–14 d. (Refer to specific protocols) SUPPLIED: Inj 10,000 IU NOTES: Toxicity symptoms: Hypersensitivity reactions in 20–35% (spectrum of urticaria to anaphy- laxis), test dose recommended; rare GI toxicity (mild nausea/anorexia, pancreatitis) Aspirin (Bayer, St. Joseph, others) COMMON USES: Mild pain, headache, fever, inflammation, prevention of emboli, and prevention of MI ACTIONS: Prostaglandin inhibitor DOSAGE: Adults. Pain, fever: 325–650 mg q4–6h PO or PR. RA: 3–6 g/d PO in ÷ doses. Platelet inhibitory action: 325 mg PO qd. Prevention of MI: 160–325 mg PO qd. Peds. Caution: Use linked to Reye’s syndrome; avoid use with viral illness in children. Antipyretic: 10–15 mg/kg/dose PO or PR q4h up to 80 mg/kg/24h. RA: 60–100 mg/kg/24h PO ÷ q4–6h (monitor serum levels to maintain between 15 and 30 mg/dL) 22 500 Clinician’s Pocket Reference, 9th Edition SUPPLIED: Tabs 325, 500 mg; chewable tabs 81 mg; EC tabs 165, 325, 500, 650, 975 mg; SR tabs 650, 800 mg; effervescent tabs 325, 500 mg; supp 120, 200, 300, 600 mg NOTES: GI upset and erosion common adverse reactions; discontinue use 1 wk prior to surgery to avoid postoperative bleeding complications Aspirin and Butalbital Compound (Fiorinal, Lanorinal, others) [C] COMMON USES: Tension headache, pain ACTIONS: Combination barbiturate and analgesic DOSAGE: 1–2 PO q4h PRN, max 6 tabs/d SUPPLIED: Caps Fiorgen PF, Fiorinal, Lanorinal, Marnal: Aspirin 325 mg/butalbital 50 mg/ caffeine 40 mg. Tabs Fiorinal, Lanorinal, Marnal: Aspirin 325 mg/butalbital 50 mg/ caffeine 40 mg NOTES: Butalbital habit-forming Aspirin + Butalbital, Caffeine and Codeine (Fiorinal + Codeine) [C] COMMON USES: Mild pain; headache, especially when associated with stress ACTIONS: Sedative analgesic, narcotic analgesic DOSAGE: 1–2 tabs (caps) PO q4–6h PRN SUPPLIED: Each cap or tab contains 325 mg aspirin, 40 mg caffeine, 50 mg of butalbital, codeine: No. 3 = 30 mg NOTES: Significant drowsiness associated with use Aspirin + Codeine (Empirin No. 2, No. 3, No. 4) [C] COMMON USES: Mild to moderate pain ACTIONS: Combined effects of aspirin and codeine DOSAGE: Adults. 1–2 tabs PO q4–6h PRN. Peds. Aspirin 10 mg/kg/dose; codeine 0.5–1.0 mg/kg/dose q4h SUPPLIED: Tabs 325 mg of aspirin and codeine as in Notes NOTES: Codeine in No. 2 = 15 mg, No. 3 = 30 mg, No. 4 = 60 mg Atenolol (Tenormin) Used for emergency cardiac care (see Chapter 21) COMMON USES: HTN, angina, MI ACTIONS: Competitively blocks β-adrenergic receptors, β1 DOSAGE: HTN and angina: 50–100 mg/d PO. AMI: 5 mg IV ×2 over 10 min, then 50 mg PO bid if tolerated SUPPLIED: Tabs 25, 50, 100 mg; inj 5 mg/10 mL Atenolol and Chlorthalidone (Tenoretic) COMMON USES: HTN ACTION: β-Adrenergic blockade with diuretic DOSAGE: 50–100 mg/d PO SUPPLIED: Tenoretic 50: Atenolol 50 mg/chlorthalidone 25 mg; Tenoretic 100: Atenolol 100 mg/chlorthalidone 25 mg Atorvastatin (Lipitor) COMMON USES: Elevated cholesterol and triglycerides ACTIONS: HMG-CoA reductase inhibitor DOSAGE: Initial dose 10 mg/d, may be ↑ to 80 mg/d SUPPLIED: Tabs 10, 20, 40, 80 mg NOTES: May cause myopathy, monitor LFT regularly Atovaquone (Mepron) 22 COMMON USES: Rx and prevention mild to moderate PCP 22 Commonly Used Medications 501 ACTIONS: Inhibits nucleic acid and ATP synthesis DOSAGE: Rx: 750 mg PO bid for 21 d. Prevention: 1500 mg PO once/d SUPPLIED: Suspension 750 mg/5 mL NOTES: Take with meals Atracurium (Tracrium) COMMON USES: Adjunct to anesthesia to facilitate endotracheal intubation ACTIONS: Nondepolarizing neuromuscular blocker DOSAGE: Adults & Peds. 0.4–0.5 mg/kg IV bolus, then 0.08–0.1 mg/kg q 20–45 min PRN SUPPLIED: Inj 10 mg/mL NOTES: Patient must be intubated and on controlled ventilation. Use adequate amounts of sedation and analgesia Atropine Used for emergency care (see Chapter 21) COMMON USES: Preanesthetic; symptomatic bradycardia and asystole ACTIONS: Antimuscarinic agent; blocks acetylcholine at parasympathetic sites DOSAGE: Adults. Emergency cardiac care, bradycardia (see Chapter 21). Preanesthetic: 0.3– 0.6 mg IM. Peds. Emergency cardiac care: 0.01–0.03 mg/kg IV q 2–5 min max 1.0 mg; min dose 0.1 mg. Preanesthetic: 0.01 mg/kg/dose SC/IV (max 0.4 mg) SUPPLIED: Tabs 0.3, 0.4, 0.6; inj 0.05, 0.1, 0.3, 0.4, 0.5, 0.8, 1.0 mg/mL NOTES: Blurred vision, urinary retention, and dried mucous membranes Azathioprine (Imuran) COMMON USES: Adjunct for the prevention of rejection following organ transplantation;

RA; SLE ACTIONS: Immunosuppressive agent; antagonizes purine metabolism DOSAGE: Adults & Peds. 1–3 mg/kg/d IV or PO SUPPLIED: Tabs 50 mg; inj 100 mg/20 mL NOTES: GI intolerance; inj should be handled with cytotoxic precautions. Interaction with allopurinol Azithromycin (Zithromax) COMMON USES: Acute bacterial exacerbations of COPD, mild community-acquired pneumonia, pharyngitis, otitis media, skin and skin structure infections, nongonococcal urethritis, and PID. Rx and prevention of MAC infections in HIV-infected persons ACTIONS: Macrolide antibiotic; inhibits protein synthesis DOSAGE: Adults. Oral: Respiratory tract infections: 500 mg on the first day, followed by 250 mg/d PO for 4 more d. Nongonococcal urethritis: 1 g as a single dose. Prevention of MAC: 1200 mg PO once/wk. IV: 500 mg for at least 2 d, followed by 500 mg PO for total of 7–10 d. Peds. Otitis media: 10 mg/kg PO on day 1, then 5 mg/kg/d on days 2–5. Pharyngitis: 12 mg/kg/d PO for 5 d SUPPLIED: Tabs 250, 600 mg; susp 1-g single-dose packet; susp 100, 200 mg/5 mL; inj 500 mg NOTES: Take susp on an empty stomach; tabs may be taken with or without food Aztreonam (Azactam) COMMON USES: Infections caused by aerobic gram (−) bacteria, including Pseudomonas aerugi- nosa ACTIONS: Monobactam antibiotic; inhibits cell wall synthesis DOSAGE: Adults. 1–2 g IV/IM q6–12h. Peds. Premature infants: 30 mg/kg/dose IV q12h. Term in- fants, children: 30 mg/kg/dose q6–8h SUPPLIED: Inj 500 mg, 1 g, 2 g NOTES: Not effective against gram (+) or anaerobic bacteria; may be given to penicillin-allergic pa- tients; adjust dose in renal impairment 22 502 Clinician’s Pocket Reference, 9th Edition Bacitracin, Topical (Baciguent) Bacitracin and Polymyxin B, Topical (Polysporin) Bacitracin, Neomycin and Polymyxin B, Topical (Neosporin Ointment) Bacitracin, Neomycin, Polymyxin B and Hydrocortisone, Topical (Cortisporin) Bacitracin, Neomycin, Polymyxin B and Lidocaine, Topical (Clomycin) COMMON USES: Prevention and Rx of minor cuts, scrapes and burns ACTIONS: Topical antibiotic with added effects based on components (antiinflammatory and anal- gesic) DOSAGE: Apply sparingly bid–qid SUPPLIED: Bacitracin 500 U/g oint. Bacitracin 500 U/polymyxin B sulfate 10,000 U/g oint and powder. Bacitracin 400 U/neomycin/ 3.5 mg/polymyxin B 5000 U/g oint (for Neosporin Cream, see page 576). Bacitracin 400 U/neomycin 3.5 mg/polymyxin B/10,000 U/hydrocortisone 10 mg/g oint. Bacitracin 500 U/neomycin 3.5 g/polymyxin B 5000 U/lidocaine 40 mg/g oint NOTES: Systemic and irrigation forms of bacitracin available but not generally used due to potential toxicity. Note: Neosporin ointment different from cream (page 576) Bacitracin, Ophthalmic (AK-Tracin Ophthalmic) Bacitracin and Polymyxin B, Ophthalmic (AK Poly Bac Ophthalmic, Polysporin Ophthalmic) Bacitracin, Neomycin and Polymyxin B, Ophthalmic (AK Spore Ophthalmic, Neosporin Ophthalmic) Bacitracin, Neomycin, Polymyxin B and Hydrocortisone, Ophthalmic (AK Spore HC Ophthalmic, Cortisporin Ophthalmic) COMMON USES: Blepharitis, conjunctivitis, and prophylactic treatment of corneal abrasions ACTIONS: Topical antibiotic with added effects based on components (antiinflammatory) DOSAGE: Apply q3–4h into conjunctival sac SUPPLIED: See Topical equivalents, above Baclofen (Lioresal, others) COMMON USES: Spasticity secondary to severe chronic disorders, eg, MS or spinal cord lesions, trigeminal neuralgia ACTIONS: Centrally acting skeletal muscle relaxant; inhibits transmission of both monosynaptic and polysynaptic reflexes at the spinal cord DOSAGE: Adults. Initially, 5 mg PO tid; ↑ q 3 d to max effect; max 80 mg/d. Peds. 2–7 y: 10–15 mg/d ÷ q8h; titrate to effect or max of 40 mg/d. >8 y: Max of 60 mg/d. IT: Through implantable pump SUPPLIED: Tabs 10, 20 mg; IT inj 10 mg/20 mL, 10 mg/5 mL NOTES: Use caution in epilepsy and neuropsychiatric disturbances, withdrawal may occur with abrupt discontinuation Basiliximab (Simulect) COMMON USES: Prevention of acute organ transplant rejections ACTIONS: IL-2 receptor antagonists DOSAGE: Adults. 20 mg IV 2 h prior to transplant, then 20 mg IV 4 d posttransplant. Peds. 12 mg/m2 up to a max of 20 mg 2 h prior to transplant, then the same dose IV 4 d posttransplant SUPPLIED: Inj 20 mg 22 NOTES: Murine/human monoclonal antibody 22 Commonly Used Medications 503 BCG [Bacillus Calmette-Guerin] (Theracys, TICE BCG) COMMON USES: Bladder carcinoma, TB prophylaxis ACTIONS: Immunomodulator DOSAGE: Bladder cancer, contents of 1 vial prepared and instilled in bladder for 2 h. Repeat once weekly for 6 wk; repeat 3 weekly doses 3, 6, 12, 18, and 24 mo after the initial therapy SUPPLIED: Inj 27 mg (3.4 + 3 × 108 CFU)/vial (TheraCys), 1–8 × 108 CFU/vial (TICE BCG) NOTES: Intravesical toxicity symptoms: Hematuria, urinary frequency, dysuria, and bacterial uri- nary tract infection. Routine adult BCG immunization in the U.S. no longer recommended. BCG vaccine occasionally used in high risk-children who are negative on the PPD skin test and cannot be given isoniazid prophylaxis. Becaplermin (Regranex Gel) COMMON USES: Adjunct to local wound care in diabetic foot ulcers ACTIONS: Recombinant human PDGF, enhanced formation of granulation tissue DOSAGE: Based on size of lesion; 1¹₃-in. ribbon from 2-g tube, ²₃-in. ribbon from 7.5- or 15-g tube/in.2 of ulcer; apply and cover with moist gauze; rinse after 12 h; do not reapply; repeat process 12 h later SUPPLIED: 0.01% gel in 2-, 7.5-, 15-g tubes NOTES: Use along with good wound care; wound must be vascularized Beclomethasone (Beclovent Inhaler, Vanceril Inhaler Quar) COMMON USES: Chronic asthma ACTIONS: Inhaled corticosteroid DOSAGE: Adults. 2–4 inhal tid–qid (max 20/d); Vanceril double strength: 2 inhal bid (max 10/d); quar 1–4 inhal bid. Peds. 1–2 inhal tid–qid (max 10/d); Vanceril double strength: 2 inhal bid (max 5/d) SUPPLIED: Oral met-dose inhaler; 42, 84 µg/inhal; quar HFA formulation 40, 80 µg/inhal NOTES: Not effective for acute asthmatic attacks; may cause oral candidiasis Beclomethasone (Beconase, Vancenase Nasal Inhaler) COMMON USES: Allergic rhinitis refractory to conventional therapy with antihistamines and decon- gestants ACTIONS: Inhaled corticosteroid DOSAGE: Adults. 1 spray intranasally bid–qid; Aqueous inhal: 1–2 spays/nostril qd–bid. Peds. 6– 12 y: 1 spray intranasally tid SUPPLIED: Nasal met-dose inhaler NOTES: Nasal spray delivers 42 µg/dose and 84 µg/dose Belladonna and Opium Supp (B & O Supprettes) [CII] COMMON USES: Bladder spasms; moderate to severe pain ACTIONS: Antispasmodic DOSAGE: Insert 1 supp PR q6h PRN. 15A = 30 mg powdered opium; 16.2 mg belladonna extract. 16A = 60 mg powdered opium; 16.2 mg belladonna extract SUPPLIED: Supp 15A, 16A NOTES: Anticholinergic side effects; caution patients about sedation, urinary retention, and consti- pation Benazepril (Lotensin) COMMON USES: HTN ACTIONS: ACE inhibitor DOSAGE: 10–40 mg/d PO SUPPLIED: Tabs 5, 10, 20, 40 mg NOTES: Symptomatic hypotension in patients taking diuretics; nonproductive cough 22 504 Clinician’s Pocket Reference, 9th Edition Benzocaine and Antipyrine (Auralgan) COMMON USES: Analgesia in severe otitis media ACTIONS: Anesthetic and local decongestant DOSAGE: Fill the ear and insert a moist cotton plug; repeat 1–2 h PRN SUPPLIED: Soln NOTES: Do not use with perforated eardrum Benzonatate (Tessalon Perles) COMMON USES: Symptomatic relief of cough ACTIONS: Anesthetizes the stretch receptors in the respiratory passages DOSAGE: Adults & Peds >10 y. 100 mg PO tid SUPPLIED: Caps 100 mg NOTES: May cause sedation; do not chew or puncture the caps Benztropine (Cogentin) COMMON USES: Parkinsonism and drug-induced extrapyramidal disorders ACTIONS: Partially blocks striatal cholinergic receptors DOSAGE: Adults. 0.5–6 mg PO, IM, or IV in ÷ doses/d. Peds >3 y. 0.02–0.05 mg/kg/dose 1–2/d SUPPLIED: Tabs 0.5, 1.0, 2.0; inj 1 mg/mL NOTES: Anticholinergic side effects Bepridil (Vascor) COMMON USES: Chronic stable angina ACTIONS: Calcium channel-blocking agent DOSAGE: 200–400 mg/d PO SUPPLIED: Tabs 200, 300, 400 mg NOTES: Agranulocytosis and serious ventricular arrhythmias, including Torsades de Pointes Beractant (Survanta) COMMON USES: Prevention and Rx of RDS in premature infants ACTIONS: Replacement of pulmonary surfactant DOSAGE: 100 mg/kg administered via endotracheal tube. May be repeated 3 more × q6h for a max of 4 doses/48h SUPPLIED: Suspension 25 mg of phospholipid/mL NOTES: Administer via 4-quadrant method Betaxolol (Kerlone) COMMON USES: HTN ACTIONS: Competitively blocks β-adrenergic receptors (β1) DOSAGE: 10–20 mg/d SUPPLIED: Tabs 10, 20 mg Betaxolol, Ophthalmic (Betoptic) COMMON USES: Glaucoma ACTIONS: Competitively blocks β-adrenergic receptors (β1) DOSAGE: 1 gtt bid SUPPLIED: Soln 0.5%; susp 0.25% Bethanechol (Urecholine, Duvoid, Various) COMMON USES: Neurogenic atony of the bladder with urinary retention, acute postoperative and postpartum functional (nonobstructive) urinary retention ACTIONS: Stimulates cholinergic receptors in the smooth muscle of the bladder and GI tract DOSAGE: Adults. 10–50 mg PO tid–qid or 2.5–5 mg SC tid–qid and PRN. Peds. 0.6 mg/kg/24h 22 PO ÷ tid–qid or 0.15–2 mg/kg/d SC ÷ 3–4×/d 22 Commonly Used Medications 505 SUPPLIED: Tabs 5, 10, 25, 50 mg; inj 5 mg/mL NOTES: Contra in bladder outlet obstruction, asthma, and CAD; do NOT administer IM or IV Bicalutamide (Casodex) COMMON USES: Advanced prostate cancer (in combination with GnRH agonists such as leuprolide or goserelin) ACTIONS: Nonsteroidal antiandrogen DOSAGE: 50 mg/d SUPPLIED: Caps 50 mg NOTES: Toxicity symptoms: Hot flashes, loss of libido, impotence, diarrhea, nausea and vomiting, gynecomastia, and LFT elevation Bicarbonate (see Sodium Bicarbonate page 602) Bisacodyl (Dulcolax) COMMON USES: Constipation; preoperative bowel preparation ACTIONS: Stimulates peristalsis DOSAGE: Adults. 5–15 mg PO or 10 mg PR PRN. Peds. <2 y: 5 mg PR PRN. >2 y: 5 mg PO or 10 mg PR PRN SUPPLIED: EC tabs 5 mg; supp 10 mg NOTES: Contra in acute abdomen or bowel obstruction; do NOT chew tabs; do NOT give within 1 h of antacids or milk Bismuth Subsalicylate (Pepto-Bismol) COMMON USES: Indigestion, nausea, and diarrhea. In combination for treatment of H. pylori infec- tion ACTIONS: Antisecretory and antiinflammatory effects DOSAGE: Adults. 2 tabs or 30 mL PO PRN (max 8 doses/24h). Peds. 3–6 y: 1⁄3 tab or 5 mL PO PRN (max 8 doses/24h). 6–9 y: 2⁄3 tab or 10 mL PO PRN (max 8 doses/24h). 9–12 y: 1 tab or 15 mL PO PRN (max 8 doses/24h) SUPPLIED: Chewable tabs 262 mg; liq 262, 524 mg/15 mL NOTES: May turn tongue and stools black Bisoprolol (Zebeta) COMMON USES: HTN ACTIONS: Competitively blocks β-adrenergic receptors (β1) DOSAGE: 5–10 mg/d (max dose 20 mg/d) SUPPLIED: Tabs 5, 10 mg Bitolterol (Tornalate) COMMON USES: Prophylaxis and Rx of asthma and reversible bronchospasm ACTIONS: Sympathomimetic bronchodilator; stimulates β2-adrenergic receptors in the lungs DOSAGE: Adults & Children. >12 y: 2 inhal q8h; acute 2 inhal 1–3 min apart, repeat × 1 SUPPLIED: Aerosol 0.8% Bleomycin Sulfate (Blenoxane) COMMON USES: Testicular carcinomas; Hodgkin’s and non-Hodgkin’s lymphomas; cutaneous lymphomas; and squamous cell carcinomas of the head and neck, larynx, cervix, skin, and penis ACTIONS: Induces breakage (scission) of single- and double-stranded DNA DOSAGE: 10–20 mg (U)/m2 1–2/wk (Refer to specific protocols) SUPPLIED: Inj 15 mg (15 U) NOTES: Toxicity symptoms: Hyperpigmentation (skin staining) and hypersensitivity (rash to ana- phylaxis); test dose of 1 mg (U) recommended, especially in lymphoma patients; fever in 50%; 22 506 Clinician’s Pocket Reference, 9th Edition lung toxicity (idiosyncratic and dose-related); pneumonitis may progress to fibrosis. Lung toxicity likely when the total dose >400 mg (U) Bretylium COMMON USES: Acute Rx of VF or tachycardia unresponsive to conventional therapy ACTIONS: Class III antiarrhythmic DOSAGE: Adults. 5 mg/kg IV rapid inj (1 min); may repeat q 15–30 min with 10 mg/kg (max 30 mg/kg); maintenance 1–2 mg/min IV infusion. Peds. Same as adults, except the maintenance dose is 5 mg/kg/dose q6–8h SUPPLIED: Inj 50 mg/mL; premixed inf 1, 2, 4 mg/mL (limited availability) NOTES: Nausea and vomiting associated with rapid IV bolus; gradually ↓ dose and discontinue in 3–5 d; effects seen within the first 10–15 min; transient rise in BP seen initially; hypotension most frequent adverse effect and occurs within the first hours of treatment Brimonidine (Alphagan) COMMON USES: Open-angle glaucoma ACTIONS: α2-Adrenergic agonist DOSAGE: 1 gtt in eye(s) tid SUPPLIED: 0.2% soln Brinzolamide (Azopt) COMMON USES: Open-angle glaucoma ACTIONS: Carbonic anhydrase inhibitor DOSAGE: 1 gtt in eye(s) tid SUPPLIED: 1.0% susp Bromocriptine (Parlodel) COMMON USES: Parkinson’s syndrome, hyperprolactinemia ACTIONS: Direct-acting on the striatal dopamine receptors; inhibits prolactin secretion DOSAGE: Initially, 1.25 mg PO bid; titrate to effect SUPPLIED: Tabs 2.5 mg; caps 5 mg NOTES: Nausea and vertigo common Buclizine (Bucladin-S Softabs) COMMON USES: Control of nausea, vomiting, and dizziness of motion sickness ACTIONS: Centrally acting antiemetic DOSAGE: 50 mg dissolved in the mouth bid; 50 mg PO prophylactically 30 min prior to travel SUPPLIED: Tabs 50 mg NOTES: NOT safe in PRG; contains tartrazine; observe the patient for allergic reactions Budesonide (Rhinocort, Pulmicort, Pulmicort Respules) COMMON USES: Allergic and nonallergic rhinitis, asthma ACTIONS: Steroid DOSAGE: Intranasal: 2 sprays/nostril bid or 4 sprays/nostril/d; Aqueous: 1 spray/nostril/d. Oral in- haled: 1–4 inhal bid. Peds. 1–2 inhal bid; Nebulization: 0.25–1 mg given qd or bid SUPPLIED:

Met-dose Turbuhaler, nasal inhaler and aqueous spray; respules 0.25 mg/2 mL, 0.5 mg/2 mL Bumetanide (Bumex) COMMON USES: Edema from CHF, hepatic cirrhosis, and renal disease ACTIONS: Loop diuretic; inhibits reabsorption of sodium and chloride in the ascending loop of Henle and the distal renal tubule DOSAGE: Adults. 0.5–2.0 mg/d PO; 0.5–1.0 mg IV q8–24h (max 10 mg/d). Peds. 0.015– 0.1 mg/kg/d PO, IV, or IM ÷ q6–24h 22 22 Commonly Used Medications 507 SUPPLIED: Tabs 0.5, 1, 2 mg; inj 0.25 mg/mL NOTES: Monitor fluid and electrolyte status during treatment Bupivacaine (Marcaine) COMMON USES: Peripheral nerve block ACTIONS: Local anesthetic DOSAGE: Adults & Peds. Dose dependent on procedure, vascularity of tissues, depth of anesthesia, and degree of muscle relaxation required (see Chapter 17) SUPPLIED: Inj 0.25, 0.5, 0.75% Buprenorphine (Buprenex) [C] COMMON USES: Moderate to severe pain ACTIONS: Opiate agonist–antagonist DOSAGE: 0.3–0.6 mg IM or slow IV push q6h PRN SUPPLIED: Inj 0.324 mg/mL (= 0.3 mg of buprenorphine) NOTES: May induce withdrawal syndrome in opioid-dependent patients Bupropion (Wellbutrin, Zyban) COMMON USES: Depression, adjunct to smoking cessation ACTIONS: Weak inhibitor of neuronal uptake of serotonin and norepinephrine; inhibits the neuronal reuptake of dopamine DOSAGE: Depression: 100–450 mg/d ÷ bid–tid. Smoking cessation: 150 mg/d for 3 d, then 150 mg bid for 8–12 wk SUPPLIED: Tabs 75, 100 mg; SR tabs 100, 150 mg NOTES: Associated with seizures; avoid use of alcohol and other CNS depressants Buspirone (Buspar) COMMON USES: Short-term relief of anxiety ACTIONS: Antianxiety agent; selectively antagonizes CNS serotonin receptors DOSAGE: 5–10 mg PO tid. ↑ dose to desired response; usual dose 20–30 mg/d; max 60 mg/d SUPPLIED: Tabs 5, 10, 15 mg NOTES: No abuse potential. No physical or psychological dependence Busulfan (Myleran) COMMON USES: CML, preparative regimens for allogeneic and ABMT in high doses ACTIONS: Alkylating agent DOSAGE: 4–12 mg/d for several weeks; 16 mg/kg once or 4 mg/kg/d for 4 d in conjunction with an- other agent in transplant regimens. Refer to specific protocol SUPPLIED: Tabs 2 mg NOTES: Toxicity symptoms: Myelosuppression, pulmonary fibrosis, nausea (high-dose therapy), gy- necomastia, adrenal insufficiency, and hyperpigmentation of the skin Butorphanol (Stadol) [C] COMMON USES: Moderate to severe pain and headaches ACTIONS: Opiate agonist–antagonist with central analgesic actions DOSAGE: 1–4 mg IM or IV q 3–4 h PRN. Headaches: 1 spray in 1 nostril, may be repeated once if pain not relieved in 60–90 min SUPPLIED: Inj 1, 2 mg/mL; nasal spray 10 mg/mL NOTES: May induce withdrawal syndrome in opioid-dependent patients Calcipotriene (Dovonex) COMMON USES: Plaque psoriasis ACTIONS: Keratolytic 22 508 Clinician’s Pocket Reference, 9th Edition DOSAGE: Apply bid SUPPLIED: Cream; oint; soln 0.005% Calcitonin (Cibacalcin, Miacalcin) COMMON USES: Paget’s disease of bone; hypercalcemia; osteogenesis imperfecta, postmenopausal osteoporosis ACTIONS: Polypeptide hormone DOSAGE: Paget’s salmon form: 100 U/d IM/SC initially, 50 U/d or 50–100 U q1–3d maintenance. Paget’s human form: 0.5 mg/d initially; maintenance 0.5 mg 2–3×/wk or 0.25 mg/d, max 0.5 mg bid. Hypercalcemia salmon calcitonin: 4 U/kg IM/SC q12h; ↑ to 8 U/kg q12h, max q6h. Osteo- porosis salmon calcitonin: 100 U/d IM/SC; Intranasal 200 U = 1 nasal spray/d SUPPLIED: Spray, nasal 200 U/activation; inj, human (Cibacalcin) 0.5 mg/vial, salmon 200 U/mL (2 mL) NOTES: Human (Cibacalcin) and salmon forms; human only approved for Paget’s bone disease Calcitriol (Rocaltrol) COMMON USES: Reduction of elevated parathyroid hormone levels, hypocalcemia associated with dialysis ACTIONS: 1,25-Dihydroxycholecalciferol, a vitamin D analogue DOSAGE: Adults. Renal failure: 0.25 µg/d PO, ↑ 0.25 µg/d q 4–6 wk PRN; 0.5 µg 3×/wk IV, ↑ PRN. Hyperparathyroidism: 0.5–2.0 µg/d. Peds. Renal failure: 15 ng/kg/d, ↑ PRN; typical main- tenance 30–60 ng/kg/d. Hyperparathyroidism: <5 y, 0.25–0.75 µg/d; >6 y, 0.5–2.0 µg/d SUPPLIED: Inj 1, 2 µg/mL (in 1 mL volume); caps 0.25, 0.5 µg NOTES: Monitor dosing to keep calcium levels within normal range Calcium Acetate (Calphron, Phos-Ex, PhosLo) COMMON USES: ESRD-associated hyperphosphatemia ACTIONS: Ca supplement to treat ESRD hypophosphatemia without aluminum DOSAGE: 2–4 tabs PO with meals SUPPLIED: Caps Phos-Ex 500 mg (125 mg Ca); Tabs Calphron and Phos-Lo 667 mg (169 mg Ca) NOTES: Can cause hypercalcemia, monitor Ca levels Calcium Carbonate (Tums, Alka-Mints) COMMON USES: Hyperacidity associated with peptic ulcer disease, hiatal hernia, etc ACTIONS: Neutralizes gastric acid DOSAGE: 500 mg–2 g PO PRN SUPPLIED: Chewable tabs 350, 420, 500, 550, 750, 850 mg; susp Calcium Glubionate (Neo-Calglucon) [OTC] COMMON USES: Rx and prevention of Ca deficiency ACTIONS: Oral Ca supplementation DOSAGE: Adults. 6–18 g/d ÷ doses. Peds. 600–2000 mg/kg/d ÷ qid (9 g/d max) SUPPLIED: OTC syrup 1.8 g/5 mL = Ca 115 mg/5 mL Calcium Salts (Chloride, Gluconate, Gluceptate) Used for emergency cardiac care (see Chapter 21) COMMON USES: Ca replacement, VF, electromechanical dissociation, Ca blocker toxicity, Mg in- toxication, tetany, hyperphosphatemia in ESRD DOSAGE: Adults. Replacement: 1–2 g/d PO. Cardiac emergencies: CaCl 0.5–1.0 g IV q 10 min or Ca gluconate 1–2 g IV q 10 min. Tetany: 1 g CaCl over 10–30 min; repeat in 6 h PRN. Peds. Re- placement: 200–500 mg/kg/24h PO or IV ÷ qid. Cardiac emergency: 100 mg/kg/dose IV of glu- conate salt q 10 min. Tetany: 10 mg/kg CaCl over 5–10 min; repeat in 6 h or use inf (200 mg/kg/d max). Adult and Peds. Hypocalcemia due to citrated blood infusion: 0.45 meq Ca/100 mL citrated 22 blood infused 22 Commonly Used Medications 509 SUPPLIED: CaCl inj 10% = 100 mg/mL = Ca 27.2 mg/mL = 10 mL ampule. Ca gluconate inj 10% = 100 mg/mL = Ca 9 mg/mL; tabs 500 mg = 45 mg Ca, 650 mg = 58.5 mg , 975 mg = 87.75 mg Ca, 1 g = 90 mg Ca. Ca gluceptate inj 220 mg/mL = 18 mg/mL Ca NOTES: CaCl contains 270 mg (13.6 meq) elemental Ca/g, and calcium gluconate contains 90 mg (4.5 meq) Ca/g. RDA for Ca: Adults = 800 mg/d, Peds = <6 mo 360 mg/d, 6 mo–1 y 540 mg/d, 1–10 y 800 mg/d; 10–18 y 1200 mg/d Calfactant (Infasurf) COMMON USES: Prevention and Rx of RSD in infants ACTIONS: Exogenous pulmonary surfactant DOSAGE: 3 mL/kg instilled into lungs. May be retreated for a total of 3 doses administered 12 h apart SUPPLIED: Intratracheal susp 35 mg/mL NOTES: Monitor for cyanosis and airway obstruction during administration Candesartan (Atacand) COMMON USES: HTN ACTIONS: Angiotensin II receptor antagonists DOSAGE: 2–32 mg/d, usual dose is 16 mg/d SUPPLIED: Tabs 4, 8, 16, 32 mg Capsaicin (Capsin, Zostrix, etc) [OTC] COMMON USES: Pain due to postherpetic neuralgia, chronic neuralgia, arthritis, diabetic neuropa- thy, postoperative pain psoriasis, intractable pruritus ACTIONS: Topical analgesic DOSAGE: Apply tid–qid SUPPLIED: OTC creams; gel; lotions; roll-ons Captopril (Capoten, Various) COMMON USES: HTN, CHF, LVD, and diabetic nephropathy ACTIONS: ACE inhibitor DOSAGE: Adults. HTN: Initially, 25 mg PO bid–tid; ↑ to a maintenance dose q 1–2 wk by 25-mg increments/dose (max 450 mg/d) to desired effect. CHF: Initially, 6.25–12.5 mg PO tid; titrate to desired effect. LVD: 50 mg PO tid. Diabetic nephropathy: 25 mg PO tid. Peds. Infants <2 mo: 0.05–0.5 mg/kg/dose PO q8–24h. Children: Initially, 0.3–0.5 mg/kg/dose PO; ↑ to a max of 6 mg/kg/d SUPPLIED: Tabs 12.5, 25, 50, 100 mg NOTES: Use with caution in renal failure. Give 1 h ac; can cause rash, proteinuria, and cough; con- tra in 2nd or 3rd trimester of PRG. Carbamazepine (Tegretol) COMMON USES: Epilepsy and trigeminal neuralgia ACTIONS: Anticonvulsant DOSAGE: Adults. Initially, 200 mg PO bid; ↑ by 200 mg/d; usual 800–1200 mg/d in ÷ doses. Peds. <6 y: 5 mg/kg/d, ↑ to 10–20 mg/kg/d ÷ in 2–4 doses. 6–12 y: Initially, 100 mg PO bid or 10 mg/kg/24h PO ÷ qd–bid; ↑ to a maintenance dose of 20–30 mg/kg/24h ÷ tid–qid SUPPLIED: Tabs 200 mg; chewable tabs 100 mg; XR tabs 100, 200, 400 mg; susp 100 mg/5 mL NOTES: Severe hematologic side effects possible; monitor CBC; monitor serum levels (see Table 22–7, pages 631–634); generic products not interchangeable Carbidopa/Levodopa (Sinemet) COMMON USES: Parkinson’s disease ACTIONS: Increases CNS levels of dopamine DOSAGE: 25/100 bid–qid; ↑ as needed (max 200/2000 mg/d) 22 510 Clinician’s Pocket Reference, 9th Edition SUPPLIED: Tabs (mg of carbidopa/mg of levodopa) 10/100, 25/100, 25/250; Tabs SR (mg of car- bidopa/mg of levodopa) 25/100, 50/200 NOTES: Psychiatric disturbances, orthostatic hypotension, dyskinesias, and cardiac arrhythmias Carboplatin (Paraplatin) COMMON USES: Ovarian, lung (small-cell and non-small-cell), head and neck, testicular, and brain cancers, and allogeneic and ABMT in high doses ACTIONS: DNA cross-linker; forms DNA–platinum adducts DOSAGE: 360 mg/m2 (ovarian carcinoma); AUC dosing 4–7 mg/mL (using Calvert’s formula: mg = AUC × [25 + calculated GFR]); also may be adjusted based on pretreatment platelet count, CrCl, and BSA (Egorin’s formula); up to 1500 mg/m2 used in ABMT setting (refer to specific protocols) SUPPLIED: Inj 50, 150, 450 mg NOTES: Toxicity symptoms: Myelosuppression, nausea and vomiting, diarrhea, nephrotoxicity, hematuria, neurotoxicity, and hepatic enzyme elevations; physiologic dosing based on either Calvert’s or Egorin’s formula allows larger doses to be given with reduced toxicity Carisoprodol (Soma) COMMON USES: Adjunct to sleep and physical therapy for the relief of painful musculoskeletal conditions ACTIONS: Centrally acting muscle relaxant DOSAGE: 350 mg PO tid–qid SUPPLIED: Tabs 350 mg NOTES: Avoid alcohol and other CNS depressants; available in combination with aspirin or codeine Carmustine (BCNU, BiCNU) COMMON USES: Primary brain tumors, melanoma, Hodgkin’s and non-Hodgkin’s lymphomas, multiple myeloma, and preparative regimens for allogeneic and ABMT in high doses ACTIONS: Alkylating agent; forms DNA cross-links; inhibitor of DNA synthesis DOSAGE: 75–100 mg/m2/d for 2 d; 200 mg/m2 in a single dose; 450–900 mg/m2 in BMT regimens (refer to specific protocols) SUPPLIED: Inj 100 mg; wafer: 7.7 mg NOTES: Toxicity symptoms: Myelosuppression (especially leukocytes and platelets), phlebitis, fa- cial flushing, hepatic and renal dysfunction, pulmonary fibrosis, and optic neuroretinitis. Hemato- logic toxicity may persist up to 4–6 wk after administration Carteolol (Cartrol, Occupress Ophthalmic) COMMON USES: HTN, increased intraocular pressure ACTIONS: Competitively blocks β-adrenergic receptors, β1, β2, ISA DOSAGE: PO 2.5–5 mg/; ophth 1 gtt in eye(s) bid SUPPLIED: Tabs 2.5, 5 mg; ophth soln 1% Carvedilol (Coreg) COMMON USES: HTN and CHF ACTIONS: Competitively blocks β-adrenergic receptors, β1, β2, α DOSAGE: HTN: 6.25–12.5 mg bid. CHF: 3.125–25 mg bid SUPPLIED: Tabs 3.125, 6.25, 12.5, 25 mg NOTES: Take with food to slow absorption and reduce incidence of orthostatic hypotension Cefaclor (Ceclor) COMMON USES: Infections caused by susceptible bacteria involving the upper and lower respira- tory tract, skin, bone, urinary tract, abdomen and gynecologic system ACTIONS: 2nd-Generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 250–500 mg PO tid. Peds. 20–40 mg/kg/d PO ÷ tid 22 22 Commonly Used Medications 511 SUPPLIED: Caps 250, 500 mg; ER tabs 375, 500 mg; susp 125, 187, 250, 375 mg/5 mL NOTES: Has more gram (–) activity then 1st-generation cephalosporins Cefadroxil (Duricef, Ultracef) COMMON USES: Infections caused by susceptible strains of Streptococcus, Staphylococcus, E. coli, Proteus and Klebsiella involving the skin, bone, upper and lower respiratory tract, and urinary tract ACTIONS: 1st-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 500–1000 mg PO bid–qd. Peds. 30 mg/kg/d ÷ bid SUPPLIED: Caps 500 mg; tabs 1 g; susp 125; 250, 500 mg/5 mL Cefazolin (Ancef, Kefzol) COMMON USES: Infections caused by susceptible strains of Streptococcus, Staphylococcus, E. coli, Proteus, and Klebsiella involving the skin, bone, upper and lower respiratory tract, and urinary tract ACTIONS: 1st-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 1–2 g IV q8h. Peds. 50–100 mg/kg/d IV ÷ q8h SUPPLIED: Inj NOTES: Widely used for surgical prophylaxis Cefdinir (Omnicef) COMMON USES: Infections caused by susceptible bacteria involving the respiratory tract, skin, bone, and urinary tract ACTIONS: 3rd-Generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 300 mg PO bid or 600 mg/d PO. Peds. 7 mg/kg PO bid or 14 mg/kg/d PO SUPPLIED: Caps 300 mg; susp 125 mg/5 mL Cefepime (Maxipime) COMMON USES: UTI and pneumonia caused by susceptible S. pneumoniae, S. aureus, K. pneumo- niae, E. coli, P. aeruginosa, and Enterobacter spp ACTIONS: 4th-generation cephalosporin; inhibits cell wall synthesis DOSAGE: 1–2 g IV q12h SUPPLIED: Inj 500 mg, 1 g, 2 g Cefixime (Suprax) COMMON USES: Infections caused by susceptible bacteria involving the respiratory tract, skin, bone, and urinary tract ACTIONS: 3rd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 200–400 mg PO qd–bid. Peds. 8 mg/kg/d PO ÷ qd–bid SUPPLIED: Tabs 200, 400 mg; susp 100 mg/5 mL NOTES: Use susp to treat otitis media Cefmetazole (Zefazone) COMMON USES: Infections caused by susceptible

bacteria involving the upper and lower respira- tory tract, skin, bone, urinary tract, abdomen and gynecologic system ACTIONS: 2nd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 1–2 mg IV q8h SUPPLIED: Inj NOTES: Has more gram (–) activity than 1st-generation cephalosporins; has anaerobic activity; ↑ risk of bleeding Cefonicid (Monocid) COMMON USES: Susceptible bacterial infections (respiratory tract, skin, bone and joint, urinary tract, gynecologic system, sepsis) ACTIONS: 2nd-generation cephalosporin 22 512 Clinician’s Pocket Reference, 9th Edition DOSAGE: 1 g/24h IM/IV SUPPLIED: Injectable forms Cefoperazone (Cefobid) COMMON USES: Susceptible bacterial infections (respiratory, skin, urinary tract, sepsis; as a 3rd-generation cephalosporin, cefoperazone has activity against gram (−) organisms (eg, E. coli, Klebsiella); variable activity against Streptococcus and Staphylococcus spp.; active against P. aeruginosa, but less than ceftazidime ACTIONS: 3rd-generation cephalosporin DOSAGE: Adults. 2–4 g/d IM/IV ÷ q12h (12 g/d max). Peds. 100–150 mg/kg/d IM/IV ÷ bid–tid SUPPLIED: Injectable forms Cefotaxime (Claforan) COMMON USES: Infections caused by susceptible bacteria involving the respiratory tract, skin, bone, urinary tract, meningitis, sepsis ACTIONS: 3rd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 1–2 g IV q4–12h. Peds. 100–200 mg/kg/d IV ÷ q6–8h SUPPLIED: Inj Cefotetan (Cefotan) COMMON USES: Infections caused by susceptible bacteria involving the upper and lower respira- tory tract, skin, bone, urinary tract, abdomen and gynecologic system ACTIONS: 2nd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 1–2 g IV q12h. Peds. 40–80 mg/kg/d IV ÷ q12h SUPPLIED: Inj NOTES: Has more gram (−) activity than 1st-generation cephalosporins; has anaerobic activity; contains MTT side chain, which may increase risk of bleeding Cefoxitin (Mefoxin) COMMON USES: Infections caused by susceptible bacteria involving the upper and lower respira- tory tract, skin, bone, urinary tract, abdomen and gynecologic system ACTIONS: 2nd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 1–2 mg IV q6h. Peds. 80–160 mg/kg/d ÷ q4–6h SUPPLIED: Inj NOTES: Has more gram (−) activity than 1st-generation cephalosporins; has anaerobic activity Cefpodoxime (Vantin) COMMON USES: Infections caused by susceptible bacteria involving the respiratory tract, skin, and urinary tract ACTIONS: 3rd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 200–400 mg PO q12h. Peds. 10 mg/kg/d PO ÷ bid SUPPLIED: Tabs 100, 200 mg; susp 50, 100 mg/5 mL NOTES: Drug interactions with agents increasing gastric pH Cefprozil (Cefzil) COMMON USES: Infections caused by susceptible bacteria involving the upper and lower respira- tory tract, skin, and urinary tract ACTIONS: 2nd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 250–500 mg PO qd–bid. Peds. 7.5–15 mg/kg/d PO ÷ bid SUPPLIED: Tabs 250, 500 mg; susp 125, 250 mg/5 mL NOTES: Has more gram (−) activity then 1st-generation cephalosporins; use higher doses for otitis 22 and pneumonia 22 Commonly Used Medications 513 Ceftazidime (Fortaz, Ceptaz, Tazidime, Tazicef) COMMON USES: Infections caused by susceptible bacteria involving the respiratory tract, skin, bone, urinary tract, meningitis, and septicemia ACTIONS: 3rd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 1–2 g IV q8h. Peds. 30–50 mg/kg/d IV ÷ q8h SUPPLIED: Inj Ceftibutin (Cedax) COMMON USES: Infections caused by susceptible bacteria involving the respiratory tract, skin, and urinary tract ACTIONS: 3rd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 400 mg/d PO. Peds. 9 mg/kg/d PO SUPPLIED: Caps 400 mg; susp 90, 180 mg/5 mL NOTES: Take on an empty stomach; little activity against Streptococcus Ceftizoxime (Cefizox) COMMON USES: Infections caused by susceptible bacteria involving the respiratory tract, skin, bone, urinary tract, meningitis, and septicemia ACTIONS: 3rd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 1–2 g IV q 8–12h. Peds. 150–200 mg/kg/d IV ÷ q6–8h SUPPLIED: Inj Ceftriaxone (Rocephin) COMMON USES: Infections caused by susceptible bacteria involving the respiratory tract, skin, bone, urinary tract, meningitis, and septicemia ACTIONS: 3rd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 1–2 g IV q12–24h. Peds. 50–100 mg/kg/d IV ÷ q12–24h SUPPLIED: Inj Cefuroxime (Ceftin [oral], Zinacef [parenteral]) COMMON USES: Infections caused by susceptible bacteria involving the upper and lower respira- tory tract, skin, bone, urinary tract, abdomen and gynecologic system ACTIONS: 2nd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 750 mg–1.5 g IV q8h or 250–500 mg PO bid. Peds. 100–150 mg/kg/d IV ÷ q8h or 20–30 mg/kg/d PO ÷ bid SUPPLIED: Tabs 125, 250, 500 mg; susp 125, 250 mg/5 mL; inj forms NOTES: Has more gram (−) activity then 1st-generation cephalosporin; IV crosses the blood–brain barrier Celecoxib (Celebrex) COMMON USES: Osteoarthritis and RA ACTIONS: NSAID, inhibits the COX-2 pathway DOSAGE: 100–200 mg/d or bid SUPPLIED: Caps 100, 200 mg Cephalexin (Keflex, Keftab) COMMON USES: Infections caused by susceptible strains of Streptococcus, Staphylococcus, E. coli, Proteus, and Klebsiella involving the skin, bone, upper and lower respiratory tract, and urinary tract ACTIONS: 1st-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 250–500 mg PO qid. Peds. 25–100 mg/kg/d PO ÷ qid SUPPLIED: Caps 250, 500 mg; tabs 250, 500, 1000 mg; susp 125; 250 mg/5 mL 22 514 Clinician’s Pocket Reference, 9th Edition Cephapirin (Cefadyl) COMMON USES: Respiratory, skin, urinary tract, bone and joint infections, endocarditis, sepsis due to susceptible gram (+) cocci (not enterococcus); some gram (−) coverage (E. coli, Proteus, Kleb- siella) ACTIONS: 1st-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 1 g IM/IV q6h (12 g/d max). Peds. 10–20 mg/kg q6h (4 g/d max) SUPPLIED: Powder for inj Cephradine (Velosef) COMMON USES: Various bacterial infections (includes group A β-hemolytic strep) ACTIONS: 1st-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 2–4 g/d PO/IV ÷ qid (8 gm/d max). Peds. >9 mo: 25–100 mg/kg/d ÷ bid–qid (4 gm/d max) SUPPLIED: Caps: 250, 500 mg; powder for susp 125 ,250 mg/5 mL, injectable Cerivastatin (Baycol) COMMON USES: Reduction of cholesterol, triglycerides and apolipoprotein B ACTIONS: HMG-CoA reductase inhibitor DOSAGE: 0.4 mg/d in the evening SUPPLIED: Withdrawn by manufacturer NOTES: May cause myopathy, monitor LFT regularly Cetirizine (Zyrtec) COMMON USES: Allergic rhinitis and chronic urticaria ACTIONS: Nonsedating antihistamine DOSAGE: Adults & Children. >6 y: 5–10 mg/d SUPPLIED: Tabs 5, 10 mg; syrup 5 mg/5 mL Charcoal, Activated (Superchar, Actidose, Liqui-Char) COMMON USES: Emergency treatment in poisoning by most drugs and chemicals ACTIONS: Adsorbent detoxicant DOSAGE: See also Chapter 21. Adults. Acute intoxication: 30–100 g/dose. GI dialysis: 25–50 g q4–6h. Peds. Acute intoxication: 1–2 g/kg/dose. GI dialysis: 5–10 g/dose q4–8h SUPPLIED: Powder, liq NOTES: Administer with a cathartic; some liq dosage forms in sorbitol base; protect the airway in lethargic or comatose patients Chloral Hydrate (Noctec, etc) [C] COMMON USES: Nocturnal and preoperative sedation ACTIONS: Sedative hypnotic DOSAGE: Adults. Hypnotic: 500 mg–1 g PO or PR 30 min prior to hs or procedure. Sedative: 250 mg PO or PR tid. Peds. Hypnotic: 20–40 mg/kg/24h PO or PR 30 min prior to hs or procedure. Sedative: 25–50 mg/kg/d ÷ q6–8h SUPPLIED: Caps 500 mg; syrup 250, 500 mg/5 mL; supp 324, 500, 648 mg NOTES: Mix syrup in a glass of water or fruit juice Chlorambucil (Leukeran) COMMON USES: CLL, Hodgkin’s disease, Waldenström’s macroglobulinemia ACTIONS: Alkylating agent DOSAGE: 0.1–0.2 mg/kg/d for 3–6 wk or 0.4 mg/kg q 2 wk (Refer to specific protocol) SUPPLIED: Tabs 2 mg NOTES: Toxicity symptoms: Myelosuppression, CNS stimulation, nausea and vomiting, drug fever, skin rash, chromosomal damage that can result in secondary leukemias, alveolar dysplasia, and pul- 22 monary fibrosis 22 Commonly Used Medications 515 Chlordiazepoxide (Librium) [C] COMMON USES: Anxiety, tension, alcohol withdrawal, and preoperative apprehension ACTIONS: Benzodiazepine; antianxiety agent DOSAGE: Adults. Mild anxiety: 5–10 mg PO tid–qid or PRN. Severe anxiety: 25–50 mg IM, IV, or PO 3–4×/d or PRN. Alcohol withdrawal: 50–100 mg IM or IV; repeat in 2–4 h if needed, up to 300 mg in 24 h; gradually taper the daily dosage. Peds. >6 y: 0.5 mg/kg/24h PO or IM ÷ q6–8h SUPPLIED: Caps 5, 10, 25 mg; tabs 10, 25 mg; inj 100 mg NOTES: ↓ Dose in the elderly; absorption of IM doses can be erratic Chlorothiazide (Diuril) COMMON USES: HTN, edema, and CHF ACTIONS: Thiazide diuretic DOSAGE: Adults. 500 mg–1.0 g PO or IV qd–bid. Peds. 20–30 mg/kg/24h PO ÷ bid SUPPLIED: Tabs 250, 500 mg; susp 250 mg/5 mL; inj 500 mg/vial NOTES: Contra in anuria Chlorpheniramine (Chlor-Trimeton, etc) COMMON USES: Allergic reactions ACTIONS: Antihistamine DOSAGE: Adults. 4 mg PO q4–6h or 8–12 mg PO bid of SR. Peds. 0.35 mg/kg/24h PO ÷ q4–6h or 0.2 mg/kg/24h SR SUPPLIED: Tabs 4 mg; chewable tabs 2 mg; SR tabs 8, 12 mg; syrup 2 mg/5 mL; inj 10, 100 mg/mL NOTES: Anticholinergic side effects and sedation common Chlorpromazine (Thorazine) COMMON USES: Psychotic disorders, apprehension, intractable hiccups, and control of nausea and vomiting ACTIONS: Phenothiazine antipsychotic; antiemetic DOSAGE: Adults. Psychosis: 10–25 mg PO or PR bid–tid. (Usual dose 30–800 mg/d in ÷ doses). Children. Psychosis & N+V: 0.5–1 mg/kg/dose PO q or IM/IV q6–8h. Severe symptoms: 25 mg IM; can repeat in 1 h; then 25–50 mg PO or PR tid. Hiccups: 25–50 mg PO bid–tid SUPPLIED: Tabs 10, 25, 50, 100, 200 mg; SR caps 30, 75, 150 mg; syrup 10 mg/5 mL; conc 30, 100 mg/mL; supp 25, 100 mg; inj 25 mg/mL NOTES: Beware of extrapyramidal side effects and sedation; has α-adrenergic-blocking properties Chlorpropamide (Diabinese) COMMON USES: Type 2 DM ACTION: Sulfonylurea. Stimulates the release of insulin from the pancreas; increases insulin sensi- tivity at peripheral sites; reduces glucose output from the liver DOSAGE: 100–500 mg/d SUPPLIED: Tabs 100, 250 mg NOTES: Use with caution in renal insufficiency Chlorthalidone (Hygroton, others) COMMON USES: HTN, edema associated with CHF ACTIONS: Thiazide diuretic DOSAGE: Adults. 50–100 mg/d PO qd. Peds. 2 mg/kg/dose PO 3×/wk or 1–2 mg/kg/d PO SUPPLIED: Tabs 15, 25, 50, 100 mg NOTES: Contra in anuric patients Chlorzoxazone (Paraflex, Parafon Forte DSC, others) COMMON USES: Adjunct to rest and physical therapy for the relief of discomfort associated with acute, painful musculoskeletal conditions ACTIONS: Centrally acting skeletal muscle relaxant 22 516 Clinician’s Pocket Reference, 9th Edition DOSAGE: Adults. 250–500 mg PO tid–qid. Peds. 20 mg/kg/d in 3–4 ÷ doses SUPPLIED: Tabs 250, 500 mg; caps 250, 500 mg Cholecalciferol [Vitamin D3] (Delta-D) COMMON USES: Dietary supplement for treatment of vitamin D deficiency ACTIONS: Enhances intestinal calcium absorption DOSAGE: 400–1000 IU/d PO SUPPLIED: Tabs 400, 1000 IU NOTES: 1 mg of cholecalciferol = 40,000 IU of vitamin D activity Cholestyramine (Questran) COMMON USES: Adjunctive therapy for the reduction of serum cholesterol in patients with primary hypercholesterolemia; Rx pruritus associated with partial biliary obstruction ACTIONS: Binds bile acids in the intestine to form insoluble complexes DOSAGE: Adults. Individualize the dose:4 g/d–bid (↑ to max 24 g/d and 6 doses/d). Peds. 240 mg/kg/d in 3 ÷ doses SUPPLIED: 4 g of cholestyramine resin/9 g of powder; with aspartame: 4 g resin/5 g of powder NOTES: Mix 4 g of cholestyramine in 2–6 oz of noncarbonated beverage; take other medications 1–2 h before or 6 h after cholestyramine Ciclopirox (Loprox) COMMON USES: Tinea pedis, tinea cruris, tinea corporis, cutaneous candidiasis, tinea versicolor ACTIONS: Antifungal antibiotic DOSAGE: Adults & Peds. >10: Massage into affected area bid SUPPLIED: Cream; gel; lotion 1% Cidofovir (Vistide) COMMON USES: CMV retinitis ACTIONS: Selective inhibition of viral DNA synthesis DOSAGE: Rx: 5 mg/kg IV once/wk for 2 wk; administered with probenecid. Maintenance: 5 mg/kg IV once/2 wk; administered with probenecid. Probenecid: 2 g PO 3 h prior to Cidofovir, and then 1 g PO at 2 h and 8 h after Cidofovir SUPPLIED: Inj 75 mg/mL NOTES: Dose adjust in renal impairment, hydrate patient with NS prior to each infusion; causes renal toxicity Cimetidine (Tagamet, others) COMMON USES: Duodenal ulcer; ulcer prophylaxis in hypersecretory states, eg, trauma, burns, surgery, ZE; and GERD ACTIONS: Histamine-2 receptor antagonist DOSAGE: Adults. Active ulcer: 2400 mg/d IV cont inf or 300 mg IV q6; 400 mg PO bid or 800 mg hs. Maintenance therapy: 400 mg PO hs. GERD: 800 mg PO bid; maintenance 800 mg PO hs. Peds. Infants: 10–20 mg/kg/24h PO or IV ÷ q6–12h. Children: 20–40 mg/kg/24h PO or IV ÷ q6h SUPPLIED: Tabs 200, 300, 400, 800 mg; liq 300 mg/5 mL; inj 300 mg/2 mL NOTES: Extend dosing interval with renal insufficiency; ↓ dose in the elderly Ciprofloxacin (Cipro) COMMON USES: Broad-spectrum activity against a variety of gram (+) and gram (−) aerobic bacteria ACTIONS: Quinolone antibiotic; inhibits DNA gyrase DOSAGE: Adults. 250–750 mg PO q12h or 200–400 mg IV q12h. Peds. NOT recommended for children <18 y old SUPPLIED: Tabs 100, 250, 500, 750 mg; susp 5 g/100 mL, 10 g/100 mL; inj 200, 400 mg NOTES: Little activity against

streptococci; drug interactions with theophylline, caffeine, sucralfate, 22 and antacids; nausea, vomiting, and abdominal discomfort common side effects; contra in PRG 22 Commonly Used Medications 517 Ciprofloxacin, Ophthalmic (Ciloxan) COMMON USES: Rx and prevention of ocular infections eg, conjunctivitis, blepharitis, corneal abra- sions ACTIONS: Quinolone antibiotic; inhibits DNA gyrase, antiinflammatory DOSAGE: Instill 1–2 gtt in eye(s) q2h while awake for 2 d, then 1–2 gtt q4h while awake for 5 more d SUPPLIED: Soln 3.5 mg/mL Ciprofloxacin, Otic (Cipro HC Otic) COMMON USES: Otitis externa ACTIONS: Quinolone antibiotic; inhibits DNA gyrase DOSAGE: Adult and Peds >1 mo. 1–2 gtt in ear(s) bid for 7 d SUPPLIED: Susp ciprofloxacin 0.2% and hydrocortisone 1% Cisplatin (Platinol) COMMON USES: Testicular, small-cell and non-small-cell lung, bladder, ovarian, breast, head and neck, and penile cancers; osteosarcoma; and pediatric brain tumors ACTIONS: DNA-binding; intrastrand cross-linking; formation of DNA adducts DOSAGE: 20 mg/m2/d for 5 d q 3 wk; 120 mg/m2 q 3–4 wk; 100 mg/m2 on days 1 and 8 q 20 d. (Refer to specific protocols) SUPPLIED: Inj 1 mg/mL NOTES: Toxicity symptoms: Allergic reactions, nausea and vomiting, nephrotoxicity (exacerbated by concurrent administration of other nephrotoxic drugs and minimized by saline infusion and mannitol diuresis), high-frequency hearing loss in approximately 30%, peripheral “stocking glove”-type neuropathy, cardiotoxicity (ST-T-wave changes), hypomagnesemia, mild myelosup- pression, and hepatotoxicity. Renal impairment is dose-related and cumulative Citalopram (Celexa) COMMON USES: Depression ACTIONS: SSRI DOSAGE: Initial 20 mg/d, may be ↑ to 40 mg/d SUPPLIED: Tabs 20, 40 mg Cladribine (Leustatin) COMMON USES: HCL ACTIONS: Induces DNA strand breakage and interference with DNA repair enzymes and DNA syn- thesis DOSAGE: 0.09 mg/kg/d cont IV inf for 7 d. (Refer to specific protocols) SUPPLIED: Inj 1 mg/mL NOTES: Toxicity symptoms: Myelosuppression; T-lymphocyte suppression may be prolonged (26–34 wk). Fever occur in 46% (probably related to tumor lysis); infections common (especially at lung and IV catheter sites); rash common (50%) in patients treated for HCL Clarithromycin (Biaxin) COMMON USES: Upper and lower respiratory tract infections, skin and skin structure infections, H. pylori infections, and infections caused by nontuberculosis (atypical) Mycobacterium. Preven- tion of MAC infections in HIV-infected individuals. ACTIONS: Macrolide antibiotic; inhibits protein synthesis DOSAGE: Adults. 250–500 mg PO bid or 1000 mg (2 × 500 mg ER tab)/d. Mycobacterium: 500–1000 mg PO bid. Peds. 7.5 mg/kg/dose PO bid SUPPLIED: Tabs 250, 500 mg; susp 125, 250 mg/5 mL; 500 mg ER tab NOTES: Increases theophylline and carbamazepine levels; avoid concurrent use with cisapride; causes metallic taste 22 518 Clinician’s Pocket Reference, 9th Edition Clemastine Fumarate (Tavist) COMMON USES: Allergic rhinitis ACTIONS: Antihistamine DOSAGE: Adults & Peds. >12 y: 1.34 mg bid to 2.68 mg tid; max 8.04 mg/d. <12 y: 0.4 mg PO bid SUPPLIED: Tabs 1.34, 2.68 mg; syrup 0.67 mg/5 mL Clindamycin (Cleocin, Cleocin-T) COMMON USES: Susceptible strains of streptococci, pneumococci, staphylococci, and gram (+) and gram (−) anaerobes; no activity against gram (−) aerobes and bacterial vaginosis; topical for severe acne and vaginal infections ACTIONS: Bacteriostatic; interferes with protein synthesis DOSAGE: Adults. 150–450 mg PO qid; 300–600 mg IV q6h or 900 mg IV q8h. Vaginal: 1 applica- torful hs for 7 d. Topical: Apply 1% gel, lotion, or soln bid. Peds. Neonates: 10–15 mg/kg/24h ÷ q8–12h. Children >1 mo: 10–30 mg/kg/24h ÷ q6–8h, to a max of 1.8 g/d oral or 4.8 g/d IV. Topical: Apply 1%, gel, lotion, or soln bid SUPPLIED: Caps 75, 150, 300 mg; susp 75 mg/5 mL; inj 300 mg/2 mL; vaginal cream 2% NOTES: Beware of diarrhea that may represent pseudomembranous colitis caused by Clostridium difficile Clofazimine (Lamprene) COMMON USES: Leprosy and as part of combination therapy for MAC in AIDS patients ACTIONS: Bactericidal; inhibits DNA synthesis DOSAGE: Adults. 100–300 mg PO qd. Peds. 1 mg/kg/d SUPPLIED: Caps 50 mg NOTES: Take with meals; may change skin pigmentation pink to brownish black; may cause skin dryness and GI intolerance Clonazepam (Klonopin) [C] COMMON USES: Lennox–Gastaut syndrome, akinetic and myoclonic seizures, and absence seizures ACTIONS: Benzodiazepine; anticonvulsant DOSAGE: Adults. 1.5 mg/d PO in 3 ÷ doses; ↑ by 0.5–1.0 mg/d q 3 d PRN up to 20 mg/d. Peds. 0.01–0.03 mg/kg/24h PO ÷ tid; ↑ to 0.1–0.2 mg/kg/24h ÷ tid SUPPLIED: Tabs 0.5, 1.0, 2.0 mg NOTES: CNS side effects, including sedation Clonidine, Oral (Catapres) COMMON USES: HTN; opioid and tobacco withdrawal ACTIONS: Centrally acting α-adrenergic stimulant DOSAGE: Adults. 0.10 mg PO bid adjusted daily by 0.1- to 0.2-mg increments (max 2.4 mg/d). Peds. 5–10 µg/kg/d ÷d q8–12h (max 0.9 mg/d) SUPPLIED: Tabs 0.1, 0.2, 0.3 mg NOTES: Dry mouth, drowsiness, and sedation frequent; more effective for HTN when combined with diuretics; rebound HTN can occur with abrupt cessation of doses >0.2 mg bid. (See TD dose.) Clonidine, Transdermal (Catapres TTS) COMMON USES: HTN ACTIONS: Centrally acting α-adrenergic stimulant DOSAGE: Apply 1 patch q 7 d to a hairless area on the upper arm or torso; titrate according to indi- vidual therapeutic requirements SUPPLIED: TTS-1, TTS-2, TTS-3 (programmed to deliver 0.1, 0.2, 0.3 mg, respectively, of cloni- dine/d for 1 wk) 22 NOTES: Doses >2 TTS-3 usually not associated with increased efficacy 22 Commonly Used Medications 519 Clopidogrel (Plavix) COMMON USES: Reduction of atherosclerotic events ACTIONS: Inhibits platelet aggregation DOSAGE: 75 mg/d SUPPLIED: Tabs 75 mg NOTES: Prolongs bleeding time, use with caution in persons at risk of bleeding from trauma, etc Clorazepate (Tranxene) [C] COMMON USES: Acute anxiety disorders, acute alcohol withdrawal symptoms, and adjunctive ther- apy in partial seizures ACTIONS: Benzodiazepine; antianxiety agent DOSAGE: Adults. 15–60 mg/d PO in single or ÷ doses. Elderly and debilitated patients: Initiate therapy at 7.5–15 mg/d in ÷ doses. Alcohol withdrawal: Day 1: Initially, 30 mg; followed by 30–60 mg in ÷ doses. Day 2: 45–90 mg in ÷ doses. Day 3: 22.5–45 mg in ÷ doses. Day 4: 15–30 mg in ÷ doses. Peds. 3.75–7.5 mg/dose bid, to a max of 60 mg/d ÷ bid–tid SUPPLIED: Tabs 3.75, 7.5, 11.25, 15, 22.5 mg NOTES: Monitor patients with renal and hepatic impairment because drug may accumulate; CNS depressant effects Clotrimazole (Lotrimin, Mycelex) COMMON USES: Candidiasis and tinea infections ACTIONS: Antifungal agent; alters cell wall permeability DOSAGE: Oral: One troche dissolved slowly in the mouth 5 (times)/d for 14 d. Vaginal: Cream 1 applicatorful hs for 7–14 d. Tabs 100 mg vaginally hs for 7 d or 200 mg (2 tabs) vaginally hs for 3 d or 500-mg tabs vaginally hs once. Topical: Apply bid for 10–14 d SUPPLIED: 1% cream; soln; lotion; troche 10 mg; vaginal tabs 100, 500 mg; vaginal cream 1% NOTES: Oral prophylaxis commonly used in immunosuppressed patients Clotrimazole and Betamethasone (Lotrisone) COMMON USES: Fungal skin infections ACTIONS: Imidazole antifungal and antiinflammatory DOSAGE: Apply and gently massage into the area bid from 2–4 wk SUPPLIED: Cream 15, 45 g NOTES: Contra in children and varicella Cloxacillin (Cloxapen, Tegopen) COMMON USES: Infections caused by susceptible strains of S. aureus and Streptococcus ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults. 250–500 mg PO qid. Peds. 50–100 mg/kg/d ÷ qid SUPPLIED: Caps 250, 500 mg; soln 125 mg/5 mL NOTES: Take on an empty stomach Clozapine (Clozaril) COMMON USES: Refractory severe schizophrenia ACTIONS: Tricyclic “atypical” antipsychotic agent DOSAGE: Initially, 25 mg qd–bid; ↑ dose to 300–450 mg/d over 2 wk. Maintain the patient at the lowest dose possible SUPPLIED: Tabs 25, 100 mg NOTES: Monitor blood counts frequently (weekly for the first 6 mo; then every other week) because of the risk of agranulocytosis. Drowsiness and seizures possible Cocaine [C] COMMON USES: Topical anesthetic for mucous membranes ACTIONS: Narcotic analgesic, local vasoconstrictor 22 520 Clinician’s Pocket Reference, 9th Edition DOSAGE: Apply topically lowest amount of topical soln that provides relief; 1 mg/kg max SUPPLIED: Topical soln and viscous preparations 4, 10% powder, soluble tabs (135 mg) for soln Codeine [C-II] COMMON USES: Mild to moderate pain; symptomatic relief of cough ACTIONS: Narcotic analgesic; depresses cough reflex DOSAGE: Adults. Analgesic: 15–60 mg PO or IM qid PRN. Antitussive: 10–20 mg PO q4h PRN; max 12 mg/d. Peds. Analgesic: 0.5–1.0 mg/kg/dose PO or IM q4–6h PRN. Antitussive: 1.0–1.5 mg/kg/24h PO ÷ q4h; max 30 mg/24h SUPPLIED: Tabs 15, 30, 60 mg; soln 15 mg/5 mL; inj 30, 60 mg/mL NOTES: Most often combined with acetaminophen for pain or with agents, eg, terpin hydrate as an antitussive; 120 mg IM = to 10 mg of morphine IM Colchicine COMMON USES: Acute gout ACTIONS: Inhibits migration of leukocytes; reduces production of lactic acid by leukocytes DOSAGE: Initially: 0.5–1.2 mg PO, then 0.5–0.6 mg q 1–2 h until relief or GI side effects develop (max 8 mg/d). Do not repeat for 3 d. IV: 1–3 mg, then 0.5 mg q6h until relief (max 4 mg/d) do not repeat for 7 d. Prophylaxis: PO: 0.5–0.6 mg/d or 3–4 d/wk SUPPLIED: Tabs 0.5, 0.6 mg; inj 1 mg/2 mL NOTES: Use caution in elderly and in renal impairment. Colchicine 1–2 mg IV within 24–48 h of an acute attack can be diagnostic and therapeutic in monoarticular arthritis Colesevelam (Welchol) COMMON USES: Reduction of LDL and total cholesterol ACTIONS: Bile acid sequestrant DOSAGE: 3 tabs PO bid with meals SUPPLIED: Tabs 625 mg Colestipol (Colestid) COMMON USES: Adjunctive for ↓ serum cholesterol in primary hypercholesterolemia ACTIONS: Binds bile acids in the intestine to form an insoluble complex DOSAGE: Granules: 5–30 g/d ÷ into 2–4 doses; tabs: 2–16 g/d qd–bid SUPPLIED: Tabs 1 g; granules NOTES: Do not use dry powder; mix with beverages, soups, cereals, etc Colfosceril Palmitate (Exosurf Neonatal) COMMON USES: Prophylaxis and Rx for RSD in infants ACTIONS: Synthetic lung surfactant DOSAGE: 5 mL/kg/dose administered through the endotracheal tube as soon after birth as possible and again at 12 and 24 h SUPPLIED: Suspension 108 mg NOTES: Monitor pulmonary compliance and oxygenation carefully. Pulmonary hemorrhage possi- ble in infants weighing <700 g at birth. Mucous plugging of endotracheal tube possible Cortisone See Steroids pages 628–630. (See Table 22–5, page 627 and Table 22–6, page 627.) Cromolyn Sodium (Intal, Nasalcrom, Opticrom) COMMON USES: Adjunct to the Rx of asthma; prevention of exercise-induced asthma; allergic rhinitis; ophth allergic manifestations ACTIONS: Antiasthmatic; mast cell stabilizer DOSAGE: Adults & Children >12 y. Inhal: 20 mg (as powder in caps) inhaled qid or met-dose in- 22 haler 2 puffs qid. Oral: 200 mg qid 15–20 min ac, up to 400 mg qid. Nasal instillation: Spray once 22 Commonly Used Medications 521 in each nostril 2–6 ×/d. Ophth: 1–2 gtt in each eye 4–6×/d. Peds. Inhal: 2 puffs qid of met-dose in- haler. Oral: Infants <2 y: 20 mg/kg/d in 4 ÷ doses. 2–12 y: 100 mg qid ac SUPPLIED: Oral conc 100 mg/5 mL; soln for neb 20 mg/2 mL; met-dose inhaler; nasal soln 40 mg/mL; ophth soln 4% NOTES: No benefit in acute situations; may require 2–4 wk for maximal effect in perennial allergic disorders Cyanocobalamin [Vitamin B12] COMMON USES: Pernicious anemia and other vitamin B12 deficiency states ACTIONS: Dietary supplement of vitamin B12 DOSAGE: Adults. 100 µg IM or SC qd for 5–10 d, then 100 µg IM 2×/wk for 1 mo, then 100 µg IM monthly. Peds. 100 µg/d IM or SC for 5–10 d, then 30–50 µg IM q 4 wk SUPPLIED: Tabs 25, 50, 100, 250, 500, 1000 µg; inj 30, 100, 1000 µg/mL NOTES: Oral absorption highly erratic, altered by many drugs and not recommended; for use with hyperalimentation (see Chapter 12) Cyclobenzaprine (Flexeril) COMMON USES: Adjunct to rest and physical therapy for the relief of muscle spasm associated with acute painful musculoskeletal conditions ACTIONS: Centrally acting skeletal muscle relaxant; reduces tonic somatic motor activity DOSAGE: 10 mg PO 2–4×/d SUPPLIED: Tabs 10 mg NOTES: Do not use for longer than 2–3 wk; has sedative and anticholinergic properties Cyclopentolate (Cyclogyl) COMMON USES: Diagnostic procedures requiring cycloplegia and mydriasis ACTIONS: Cycloplegia and mydriatic agent (can last up to 24 h) DOSAGE: 1 gtt followed by another in 5 min SUPPLIED: Soln, 0.5, 1, 2% Cyclophosphamide (Cytoxan, Neosar) COMMON USES: Hodgkin’s and non-Hodgkin’s lymphomas, multiple myeloma, breast and ovarian cancers, mycosis fungoides, neuroblastoma, retinoblastoma, acute leukemias, small-cell lung can- cer, and allogeneic and ABMT in high doses; severe rheumatologic disorders ACTIONS: Converted to acrolein and phosphoramide mustard, the active alkylating moieties DOSAGE: 500–1500 mg/m2 as a single dose at 2–4-wk intervals; 1.8 g/m2 to 160 mg/kg (or ≈12 g/m2 in a

75-kg individual) in the BMT setting. (Refer to specific protocols) SUPPLIED: Tabs 25, 50 mg; inj 100 mg NOTES: Toxicity symptoms: Myelosuppression (leukopenia and thrombocytopenia); sterile hemor- rhagic cystitis, SIADH, alopecia, and anorexia; nausea and vomiting common. Hepatotoxicity and rarely interstitial pneumonitis possible. Irreversible testicular atrophy possible. Cardiotoxicity rare. Second malignancies (bladder cancer and acute leukemias); cumulative risk of 3.5% at 8 y, 10.7% at 12 y. Preventive measures to avoid hemorrhagic cystitis often applied in high-dose regimens and may include continuous bladder irrigation and MESNA uroprotection (see page 567) Cyclosporine (Sandimmune, Neoral) COMMON USES: Organ rejection in kidney, liver, heart, and BMT in conjunction with adrenal corti- costeroids ACTIONS: Immunosuppressant; reversible inhibition of immunocompetent lymphocytes DOSAGE: Adults & Peds. Oral: 15 mg/kg/d beginning 12 h prior to transplant; after 2 wk, taper the dose by 5 mg/wk to 5–10 mg/kg/d. IV: If the patient is unable to take the drug orally, give 1⁄2 the oral dose IV SUPPLIED: Caps 25, 50 mg, 100 mg; oral soln 100 mg/mL; inj 50 mg/mL 22 522 Clinician’s Pocket Reference, 9th Edition NOTES: May elevate BUN and creatinine, which may be confused with renal transplant rejection; should be administered in glass containers; many drug interactions; Neoral and Sandimmune not interchangeable. (See Table 22–7 pages 631–634.) Cyproheptadine (Periactin) COMMON USES: Allergic reactions; especially good for itching ACTIONS: Phenothiazine antihistamine DOSAGE: Adults. 4–20 mg PO ÷ q8h; max 0.5 mg/kg/d. Peds. 2–6 y: 2 mg bid–tid (max 12 mg/24h). 7–14 y: 4 mg bid–tid SUPPLIED: Tabs 4 mg; syrup 2 mg/5 mL NOTES: Anticholinergic side effects and drowsiness common; may stimulate appetite in some pa- tients Cytarabine [Ara-C] (Cytosar-U) COMMON USES: Acute leukemias, CML, non-Hodgkin’s lymphoma; IT administration for leukemic meningitis or prophylaxis ACTIONS: Antimetabolite; interferes with DNA synthesis DOSAGE: 100–150 mg/m2/d for 5–10 d (low-dose); 3 g/m2 q12h for 8–12 doses (high-dose); 1 mg/kg 1–2×/wk (SC maintenance regimens); 5–70 mg/m2 up to 3×/wk IT. (Refer to specific pro- tocols) SUPPLIED: Inj 100 mg, 500 mg, 1 g, 2 g NOTES: Toxicity symptoms: Myelosuppression, nausea and vomiting, diarrhea, stomatitis, flu-like syndrome, rash of the palms and soles of the feet, and hepatic dysfunction. Toxicity of high-dose regimens (conjunctivitis) ameliorated by corticosteroid ophth soln, cerebellar dysfunction, and noncardiogenic pulmonary edema Cytarabine Liposomal (Depocyt) COMMON USES: Lymphomatous meningitis ACTIONS: Antimetabolite; interferes with DNA synthesis DOSAGE: 50 mg IT q 14 d for 5 doses; followed by 50 mg IT q 28 d for 4 doses SUPPLIED: IT inj 50 mg/5 mL Cytomegalovirus Immune Globulin [CMV-GIV] (Cytogam) COMMON USES: Attenuation of primary CMV disease associated with transplantation ACTIONS: Provides exogenous IgG antibodies to CMV DOSAGE: Administered for 16 wk posttransplant, 15 mg/kg/hr, ↑Q30 min to 60 mg/kg/hr, max 75 mL/hr IV SUPPLIED: Inj 50±10 mg/mL Dacarbazine (DTIC-Dome) COMMON USES: Melanoma, Hodgkin’s disease, sarcoma ACTIONS: Alkylating agent; antimetabolite activity as a purine precursor; inhibits synthesis of pro- tein, RNA, and especially DNA DOSAGE: 2–4.5 mg/kg/d for 10 consecutive d or 250 mg/m2/d for 5 d. (Refer to specific protocols) SUPPLIED: Inj 100, 200, 500 mg NOTES: Toxicity symptoms: Moderate myelosuppression, severe nausea and vomiting, hepatotoxic- ity, flu-like syndrome, hypotension with high-dose therapy, photosensitivity, alopecia, facial flush- ing, facial paresthesias, urticaria, and phlebitis at the inj site Daclizumab (Zenapax) COMMON USES: Prevention of acute organ rejection ACTIONS: IL-2 receptor antagonists DOSAGE: 1 mg/kg IV/dose; first dose before transplant then 4 doses 14 d apart posttransplant 22 SUPPLIED: Inj 5 mg/mL 22 Commonly Used Medications 523 Dactinomycin (Cosmegen) COMMON USES: Choriocarcinoma, Wilms’ tumor, Kaposi’s sarcoma, Ewing’s sarcoma, rhab- domyosarcoma, testicular cancer ACTIONS: DNA intercalating agent DOSAGE: 0.5 mg/d for 5 d; 2 mg/wk for 3 consecutive wk; 15 µg/kg or 0.45 mg/m2/d (max 0.5 mg) for 5 d q 3–8 wk in pediatric sarcoma. (Refer to specific protocols) SUPPLIED: Inj 0.5 mg NOTES: Toxicity symptoms: Myelosuppression, immunosuppression, nausea and vomiting, alope- cia, acne-form skin changes and hyperpigmentation, radiation recall phenomenon, phlebitis and tis- sue damage with extravascular extravasation, and hepatotoxicity Dalteparin (Fragmin) COMMON USES: Unstable angina, non-Q-wave MI, prevention of ischemic complications due to clot formation in patients on concurrent aspirin, prevention of DVT following surgery ACTIONS: Low-molecular-weight heparin DOSAGE: Angina/MI: 120 IU/kg (max 10,000 IU) SC q12h with aspirin. DVT prophylaxis: 2500–5000 IU SC 1–2 h prior to surgery, then qd for 5–10 d. Systemic anticoagulation: 200 IU/kg/d SC or 100 IU/kg bid SC SUPPLIED: Inj 2500 IU (16 mg/0.2 mL), 5000 IU (32 mg/0.2 mL), 10,000 (64 mg/mL) NOTES: Predictable antithrombotic effects eliminates need for laboratory monitoring Dantrolene (Dantrium) COMMON USES: Clinical spasticity resulting from upper motor neuron disorders, eg, spinal cord in- juries, strokes, CP, or MS; Rx of malignant hyperthermic crisis ACTIONS: Skeletal muscle relaxant DOSAGE: Adults. Spasticity: Initially, 25 mg PO qd; ↑ to effect by 25 mg to a max dose of 100 mg PO qid PRN. Peds. Initially, 0.5 mg/kg/dose bid; ↑ by 0.5 mg/kg to effectiveness to a max dose of 3 mg/kg/dose qid PRN. Adults & Peds. Malignant hyperthermia: Treatment: Continuous rapid IV push beginning at 1 mg/kg until symptoms subside or 10 mg/kg is reached. Postcrisis follow-up: 4–8 mg/kg/d in 3–4 ÷ doses for 1–3 d to prevent recurrence SUPPLIED: Caps 25, 50, 100 mg; powder for inj 20 mg/vial NOTES: Monitor ALT and AST closely Dapsone [DDS] (Avlosulfon) COMMON USES: Rx and prevention of PCP; toxoplasmosis prophylaxis; leprosy ACTIONS: Unknown; bactericidal DOSAGE: Adults. Prophylaxis of PCP 50–100 mg/d PO. Rx of PCP 100 mg/d PO with TMP 5 mg/kg for 21 d. Peds. Prophylaxis of PCP 1–2 mg/kg/24h PO qd; max 100 mg/d SUPPLIED: Tabs 25 mg, 100 mg NOTES: Absorption enhanced by an acidic environment; leprosy therapy in combination with ri- fampin and other agents Daunorubicin (Daunomycin, Cerubidine) COMMON USES: Acute leukemias ACTIONS: DNA intercalating agent; inhibits topoisomerase II; generates oxygen free radicals DOSAGE: 45–60 mg/m2/d for 3 consecutive d; 25 mg/m2/wk. (Refer to specific protocols) SUPPLIED: Inj 20 mg NOTES: Toxicity symptoms: Myelosuppression, mucositis, nausea and vomiting, alopecia, radiation recall phenomenon, hepatotoxicity (hyperbilirubinemia), tissue necrosis on extravascular extrava- sation, and cardiotoxicity (1–2% risk of CHF with a cumulative dose of 550 mg/m2) Delavirdine (Rescriptor) COMMON USES: HIV infection ACTION: Nonnucleoside reverse transcriptase inhibitor 22 524 Clinician’s Pocket Reference, 9th Edition DOSAGE: 400 mg PO tid SUPPLIED: Tabs 100 mg NOTES: Inhibits cytochrome P-450 enzymes. Numerous drug interactions Demeclocycline (Declomycin) COMMON USES: SIADH ACTIONS: Antagonizes the action of ADH on renal tubules DOSAGE: 300–600 mg PO q12h SUPPLIED: Caps 150 mg; tabs 150, 300 mg NOTES: ↓ Dose in renal failure. DI possible Desipramine (Norpramin) COMMON USES: Endogenous depression, chronic pain, and peripheral neuropathy ACTIONS: Tricyclic antidepressant; increases synaptic concentration of serotonin or norepinephrine in CNS DOSAGE: 25–200 mg/d in single or ÷ doses; usually as a single hs dose. (Max 300 mg/d) SUPPLIED: Tabs 10, 25, 50, 75, 100, 150 mg; caps 25, 50 mg NOTES: Many anticholinergic side effects, including blurred vision, urinary retention, and dry mouth Desmopressin (DDAVP, Stimate) COMMON USES: DI (intranasal and parenteral); bleeding caused by hemophilia A and type I von Willebrand’s disease (parenteral), nocturnal enuresis ACTIONS: Synthetic analogue of vasopressin, a naturally occurring human ADH; increases factor VIII DOSAGE: DI: Intranasal: Adults. 0.1–0.4 mL (10–40 µg)/d in 1–4 ÷ doses. Peds 3 mo–12 y. 0.05–0.3 mL/d in 1 or 2 doses. Parenteral: Adults. 0.5–1 mL (2–4 µg)/d in 2 ÷ doses. If converting from intranasal to parenteral dosing, use 1⁄10 of the intranasal dose. Oral: Adults. 0.05 mg bid; may be ↑ to max of 1.2 mg. Hemophilia A and von Willebrand’s disease (type I): Adults & Peds >10 kg. 0.3 µg/kg diluted to 50 mL with NS infused slowly over 15–30 min. Peds <10 kg. Same as above with dilution to 10 mL with NS. Nocturnal enuresis: Peds >6 y. 20 µg intranasally hs. SUPPLIED: Tabs 0.1, 0.2 mg; inj 4 µg/mL; nasal soln 0.1, 1.5 mg/mL NOTES: In very young and old patients adjust fluid intake to avoid water intoxication and hypona- tremia NOTES: Must be used in conjunction with a glucocorticoid Dexamethasone, Nasal (Dexacort Phosphate Turbinaire) COMMON USES: Chronic nasal inflammation or allergic rhinitis ACTIONS: Antiinflammatory corticosteroid DOSAGE: Adult and Peds > 12 y. 2 sprays/nostril bid–tid, max 12 sprays/d. Peds 6–12 y. 1–2 sprays/nostril, bid, max 8 sprays/d SUPPLIED: Aerosol, 84 µg/activation Dexamethasone, Ophthalmic (AK-DEX Ophthalmic, Decadron Ophthalmic, others) COMMON USES: Inflammatory or allergic conjunctivitis ACTIONS: Antiinflammatory corticosteroid DOSAGE: Instill 1–2 gtt tid–qid SUPPLIED: Susp and soln 0.1%; oint 0.05% Dexamethasone, Systemic, Topical (Decadron) 22 See Steroids (Table 22–5, page 627 and Table 22–6, pages 628–630) 22 Commonly Used Medications 525 Dexpanthenol (Ilopan-Choline Oral, Ilopan) COMMON USES: Minimize paralytic ileus, Rx postop distention ACTIONS: Cholinergic agent DOSAGE: Adults. Relief of gas: 2–3 tabs PO tid. Prevention of postop ileus: 250–500 mg IM stat, repeat in 2 h, then q6h PRN. Ileus: IM: 500 mg stat, repeat in 2 h, followed by doses q6h, if needed SUPPLIED: Inj; tabs 50 mg; cream NOTES: Do NOT use if obstruction is suspected Dexrazoxane (Zinecard) COMMON USES: Prevention of anthracycline-induced (doxorubicin) cardiomyopathy in metastatic breast cancer and other therapies ACTIONS: Chelates heavy metals; binds intracellular iron and prevents anthracycline-induced free- radical generation DOSAGE: 10:1 ratio of dexrazoxane to doxorubicin, 30 min prior to each dose of anthracycline SUPPLIED: Inj 10 mg/mL NOTES: Toxicity symptoms: Myelosuppression (especially leukopenia), fever, infection, stomatitis, alopecia, diarrhea, and nausea and vomiting. Mild elevations of hepatic transaminases and local pain at injection site less frequent Dextran 40 [Low Molecular Weight Dextran] (Rheomacrodex) COMMON USES: Plasma expander for adjunctive therapy in shock, prophylaxis of DVT and throm- boembolism, adjunct in peripheral vascular surgery ACTIONS: Expands plasma volume; ↓ blood viscosity DOSAGE: Shock: 10 mL/kg infused rapidly with a max dose of 20 mL/kg in the first 24 h; max dosage beyond 24 h not to exceed 10 mL/kg; discontinue after 5 d. Prophylaxis of DVT and throm- boembolism: 10 mL/kg IV on day of surgery followed by 500 mL/d IV for 2–3 d, then 500 mL IV q 2–3 d based on the patient’s risk factors for up to 2 wk SUPPLIED: 10% dextran 40 in 0.9% NaCl or 5% dextrose NOTES: Observe for hypersensitivity reactions; monitor renal function and electrolytes Dextromethorphan (Mediquell, Benylin DM, Pediacare 1) COMMON USES: Controlling nonproductive cough ACTIONS: Depresses the cough center in the medulla DOSAGE: Adults. 10–30 mg PO q4h PRN. Peds. 7 mo–1 y: 2–4 mg q6–8h; 2–6 y: 2.5–7.5 mg q4–8h (max 30 mg/24h). 7–12 y: 5–10 mg q4–8h (max 60 mg/24/h) SUPPLIED: Caps 30 mg; lozenges 2.5, 5, 7.5, 15 mg; syrup 15 mg/15 mL, 10 mg/5 mL; liq 10 mg/ 15 mL, 3.5, 7.5, 15 mg/5 mL; sustained-action liq 30 mg/5 mL NOTES: May be found in combination products with guaifenesin Dezocine (Dalgan) COMMON USES: Moderate to severe pain ACTIONS: Narcotic agonist–antagonist DOSAGE: 5–20 mg IM or 2.5–10 mg IV q2–4h PRN SUPPLIED: Inj 5, 10, 15 mg/mL NOTES: Withdrawal symptoms possible in patients dependent on narcotics. NOT recommended for patients <18 y Diazepam (Valium, others) [CIV] COMMON USES: Anxiety, alcohol withdrawal, muscle spasm, status epilepticus, panic disorders, amnesia, and preoperative sedation ACTIONS: Benzodiazepine DOSAGE: Adults. Status epilepticus: 5–10 mg q 10–20 min to max dose of 30 mg in 8-h period. Anxiety, muscle spasm: 2–10 mg PO bid–qid or IM/IV q3–4h PRN. Preop: 5–10 mg PO or IM 20–30 min before procedure; can be given IV just prior to procedure. Alcohol withdrawal: Initially, 22 526 Clinician’s Pocket Reference, 9th Edition 2–5 mg IV, then 5–10 mg q 5–10 min, not to exceed 100 mg in 1 h. May require up to 1000 mg in 24-h period for severe withdrawal symptoms. Titrate to agitation; avoid excessive sedation; may lead to aspiration or respiratory arrest. Peds. Status epilepticus: <5 y: 0.05–0.3 mg/kg/dose IV q 15–30 min up to a max of 5 mg. >5 y: May administer up to a max of 10 mg. Sedation, muscle re- laxation: 0.04–0.3 mg/kg/dose q2–4h IM or IV up to a max of 0.6 mg/kg in 8 h, or 0.12–0.8 mg/kg/24h PO ÷ tid–qid SUPPLIED: Tabs 2, 5, 10 mg; soln 1, 5 mg/mL; inj 5 mg/mL; gel for rectal delivery 5 mg/mL NOTES: Do NOT exceed 5 mg/min IV in adults or 1–2 mg/min in peds, as respiratory arrest possi- ble; absorption of IM dose may be erratic Diazoxide (Hyperstat, Proglycem)

COMMON USES: Hypoglycemia caused by hyperinsulinism ACTIONS: Inhibits pancreatic insulin release DOSAGE: Adults & Peds. 3–8 mg/kg/24h PO ÷ q8–12h. Neonates. 8–15 mg/kg/24h ÷ in 3 equal doses; maintenance 8–10 mg/kg/24h PO in 2–3 equal doses SUPPLIED: Inj 15 mg/mL; caps 50 mg; oral susp 50 mg/mL NOTES: Sodium retention and hyperglycemia frequent; possible thiazide diuretic cross-hypersensi- tivity; cannot be titrated Dibucaine (Nupercainal) COMMON USES: Hemorrhoids and minor skin conditions ACTIONS: Topical anesthetic DOSAGE: Insert PR with applicator bid and after each bowel movement; apply sparingly to skin SUPPLIED: 1% Oint with rectal applicator; 0.5% cream Diclofenac (Cataflam, Voltaren) COMMON USES: Arthritis and pain ACTIONS: NSAID DOSAGE: 50–75 mg PO bid SUPPLIED: Tabs 50 mg; tabs DR 25, 50, 75, 100 mg Dicloxacillin (Dynapen, Dycill) COMMON USES: Infections caused by susceptible strains of S. aureus and Streptococcus ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults. 250–500 mg qid. Peds <40 kg. 12.5–25 mg/kg/d ÷ qid SUPPLIED: Caps 125, 250, 500 mg; soln 62.5 mg/5 mL NOTES: Take on an empty stomach Dicyclomine (Bentyl) COMMON USES: Functional irritable bowel syndromes ACTIONS: Smooth muscle relaxant DOSAGE: Adults. 20 mg PO qid; ↑ to a max dose of 160 mg/d or 20 mg IM q6h. Peds. Infants >6 mo: 5 mg/dose tid–qid. Children: 10 mg/dose tid–qid SUPPLIED: Caps 10, 20 mg; tabs 20 mg; syrup 10 mg/5 mL; inj 10 mg/mL NOTES: Anticholinergic side effects may limit dose Didanosine [DDI] (Videx) COMMON USES: HIV infection in zidovudine-intolerant patients ACTIONS: Nucleoside antiretroviral agent DOSAGE: Adults. >60 kg: 400 mg/d PO or 200 mg PO bid. <60 kg: 250 mg/d PO or 125 mg PO bid. Peds. Dose by following table 22 22 Commonly Used Medications 527 BSA (m2) Tablets (mg) Powder (mg) 1.1–1.4 100 mg bid 125 mg bid 0.8–1 75 mg bid 94 mg bid 0.5–0.7 50 mg bid 62 mg bid <0.4 25 mg bid 31 mg bid SUPPLIED: Chewable tabs 25, 50, 100, 150, 200 mg; powder packets 100, 167, 250, 375 mg; pow- der for soln 2, 4 g NOTES: Reconstitute powder with water; side effects include pancreatitis, peripheral neuropathy, diarrhea, and headache; adults should take 2 tabs/administration. Dose adjust in renal impairment; do not mix powder with fruit juice or other acidic beverages Diflunisal (Dolobid) COMMON USES: Mild to moderate pain; osteoarthritis ACTIONS: NSAID DOSAGE: Pain: 500 mg PO bid. Osteoarthritis: 500–1500 mg PO in 2–3 ÷ doses SUPPLIED: Tabs 250, 500 mg NOTES: May prolong bleeding time Digoxin (Lanoxin, Lanoxicaps) Used for emergency cardiac care (see Chapter 21) COMMON USES: CHF, AF and flutter, and PAT ACTIONS: Positive inotrope; increases the refractory period of the AV node DOSAGE: Adults. PO digitalization: 0.50–0.75 mg PO, then 0.25 mg PO q6–8h to total 1.0–1.5 mg. IV or IM digitalization: 0.25–0.50 mg IM or IV, then 0.25 mg q4–6h to total ≅1 mg. Daily mainte- nance: 0.125–0.500 mg/d PO, IM, or IV (average daily dose 0.125–0.250 mg). Peds. Preterm in- fants: Digitalization: 30 µg/kg PO or 25 µg/kg IV; give 1⁄2 of dose initially, then 1⁄4 of dose at 8–12-h intervals for 2 doses. Maintenance: 5–7.5 µg/kg/24h PO or 4–6 µg/kg/24h IV ÷ q12h. Term in- fants: Digitalization: 25–35 µg/kg PO or 20–30 µg/kg IV; give 1⁄2 the dose initially, then 1⁄4 of the dose at 8–12 h. Maintenance: 6–10 µg/kg/24h PO or 5–8 µg/kg/24h ÷ q12h. 1 mo–2 y: Digitaliza- tion: 35–60 µg/kg PO or 30–50 µg/kg IV; give 1⁄2 the dose initially, then 1⁄4 of the dose at 8–12h in- tervals for 2 doses. Maintenance: 10–15 µg/kg/24h PO or 7.5–15 µg/kg/24h IV ÷ q12h. 2–10 y: Digitalization: 30–40 µg/kg PO or 25 µg/kg IV; give 1⁄2 dose initially, then 1⁄4 of the dose at 8–12-h intervals for 2 doses. Maintenance: 8–10 µg/kg/24h PO or 6–8 µg/kg/24h IV ÷ q12h. >10 y: Same as for adults SUPPLIED: Caps 0.05, 0.1, 0.2 mg; tabs 0.125, 0.25, 0.5 mg; elixir 0.05 mg/mL; inj 0.1, 0.25 mg/mL NOTES: Can cause heart block; low potassium can potentiate toxicity; ↓ in renal failure. Toxicity symptoms: Nausea and vomiting, headache, fatigue, visual disturbances (yellow-green halos around lights), and cardiac arrhythmias; IM inj can be painful and has erratic absorption (See Drug Levels, Table 22–7, pages 631–634) Digoxin Immune Fab (Digibind) Used for emergency cardiac care (see Chapter 21) COMMON USES: Life-threatening digoxin intoxication ACTIONS: Antigen-binding fragments bind digoxin, rendering it inactive DOSAGE: Adults & Peds. Based on serum level and patient’s weight. See dosing charts provided with the drug SUPPLIED: Inj 38 mg/vial NOTES: Each vial binds ≅0.6 mg of digoxin; in renal failure, may require redosing in several days because of breakdown of the immune complex 22 528 Clinician’s Pocket Reference, 9th Edition Diltiazem (Cardizem, Dilacor, Tiazac) Used for emergency cardiac care (see Chapter 21) COMMON USES: Angina pectoris, prevention of reinfarction, HTN, AF or flutter, and PAT ACTIONS: Calcium channel-blocker DOSAGE: Oral: Initially, 30 mg PO qid; ↑ to 180–360 mg/d in 3–4 ÷ doses PRN. SR: 60–120 mg PO bid; ↑ to effect to max dose 360 mg/d. CD: 120–360 mg/d (max 480 mg/d). IV: 0.25 mg/kg IV bolus over 2 min; may repeat the dose in 15 min at 0.35 mg/kg. May begin cont inf of 5–15 mg/h SUPPLIED: Tabs 30, 60, 90, 120 mg; SR caps 60, 90, 120 mg; CD caps 120, 180, 240, 300, 360 mg, 420 mg; inj 5 mg/mL NOTES: Contra in sick sinus syndrome, AV block, and hypotension; Cardizem CD, Dilacor XR, and Tiazac not interchangeable Dimenhydrinate (Dramamine, other) COMMON USES: Prevention and Rx of nausea, vomiting, dizziness, or vertigo of motion sickness ACTIONS: Antiemetic DOSAGE: Adults. 50–100 mg PO q4–6h to a max of 400 mg/d; 50 mg IM/IV PRN. Peds. 5 mg/kg/24h PO or IV ÷ qid (max 300 mg/d) SUPPLIED: Tabs 50 mg; chewable tabs 50 mg; liq 12.5 mg/4 mL, 12.5 mg/5 mL, 15.62 mg/5 mL; inj 50 mg/mL NOTES: Anticholinergic side effects Dimethyl Sulfoxide [DMSO] (Rimso-50) COMMON USES: Interstitial cystitis ACTIONS: Unknown DOSAGE: Intravesical, 50 mL, retain for 15 min; repeat q 2 wk until relief SUPPLIED: 50 % soln in 50 mL Diphenhydramine (Benadryl, others) COMMON USES: Allergic reactions, motion sickness, potentiate narcotics, sedation, cough suppres- sion, and treatment of extrapyramidal reactions ACTIONS: Antihistamine, antiemetic DOSAGE: Adults. 25–50 mg PO, IV, or IM bid–tid. Peds. 5 mg/kg/24h PO or IM ÷ q6h (max 300 mg/d) SUPPLIED: Tabs and caps 25, 50 mg; chewable tabs 12.5 mg; elixir 12.5 mg/5 mL; syrup 12.5 mg/5 mL; liq 6.25 mg/5 mL, 12.5 mg/5 mL; inj 50 mg/mL NOTES: Anticholinergic side effects, including dry mouth and urinary retention; causes sedation; ↑ interval in moderate to severe renal failure Diphenoxylate + Atropine (Lomotil) [C] COMMON USES: Diarrhea ACTIONS: Constipating meperidine congener DOSAGE: Adults. Initially, 5 mg PO tid–qid until under control, then 2.5–5.0 mg PO bid. Peds >2 y: 0.3–0.4 mg/kg/24h (of diphenoxylate) ÷ bid–qid SUPPLIED: Tabs 2.5 mg of diphenoxylate/0.025 mg of atropine; liq 2.5 mg diphenoxylate/0.025 mg atropine/5 mL NOTES: Atropine-type side effects Dipivefrin (Propine) COMMON USES: Open-angle glaucoma ACTIONS: α-Adrenergic agonist DOSAGE: 1 gtt into eye q12h 22 SUPPLIED: 0.1% soln 22 Commonly Used Medications 529 Dirithromycin (Dynabac) COMMON USES: Bronchitis, community-acquired pneumonia, and skin and skin structure infec- tions ACTIONS: Macrolide antibiotic DOSAGE: 500 mg/d PO SUPPLIED: Tabs 250 mg NOTES: Absorption enhanced when taken with food Disopyramide (Norpace, Napamide) COMMON USES: Suppression and prevention PVC ACTIONS: Class 1A antiarrhythmic DOSAGE: Adults. 400–800 mg/d ÷ q6h for regular-release products and q12h for SR products. Peds. <1 y: 10–30 mg/kg/24h PO (÷ qid). 1–4 y: 10–20 mg/kg/24h PO (÷ qid). 4–12 y: 10–15 mg/kg/24h PO (÷ qid). 12–18 y: 6–15 mg/kg/24h PO (÷ qid) SUPPLIED: Caps 100, 150 mg; SR caps 100, 150 mg NOTES: Anticholinergic side effects (urinary retention); negative inotropic properties may induce CHF; ↓ in impaired hepatic function and renal dysfunction. (See Table 22–7, pages 631–634, for levels.) Dobutamine (Dobutrex) Used for emergency cardiac care (see Chapter 21) COMMON USES: Short-term use in cardiac decompensation secondary to depressed contractility ACTIONS: Positive inotropic agent DOSAGE: Adults & Peds. Cont IV inf of 2.5–15 µg/kg/min; rarely, 40 µg/kg/min may be required; titrate according to response SUPPLIED: Inj 250 mg/20 mL NOTES: Monitor ECG for ↑ heart rate, BP, and ectopic activity; monitor PWP and cardiac output if possible. (See also Table 20–10, page 637.) Docetaxel (Taxotere) COMMON USES: Breast (anthracycline-resistant), ovarian, and lung cancers ACTIONS: Antimitotic agent; promotes microtubular aggregation; semisynthetic taxoid DOSAGE: 100 mg/m2 by 1-h IV infusion q 3 wk. Start dexamethasone 8 mg bid prior to docetaxel and continue for 3–4 d. (Refer to specific protocols.) SUPPLIED: Inj 20, 40, 80 mg/mL NOTES: Toxicity symptoms: Myelosuppression, neuropathy, and nausea and vomiting; fluid reten- tion syndrome cumulative doses of 300–400 mg/m2 without corticosteroid preparation and post- treatment and 600–800 mg/m2 with corticosteroid preparation. Hypersensitivity reactions possible, but only rarely with corticosteroid preparation. ↓ Dose with ↑ bilirubin levels Docusate Calcium (Surfak, others)/Docusate Potassium (Dialose)/Docusate Sodium (Doss, Colace, others) COMMON USES: Constipation; adjunct to painful anorectal conditions (hemorrhoids) ACTIONS: Stool softener DOSAGE: Adults. 50–500 mg PO ÷ qd–qid. Peds. Infants–3 y: 10–40 mg/24h ÷ qd–qid. 3–6 y: 20–60 mg/24h ÷ qd–qid.6–12 y: 40–150 mg/24h ÷ qd–qid SUPPLIED: Ca: Caps 50, 240 mg. K: Caps 100, 240 mg. Na: Caps 50, 100 mg; syrup 50, 60 mg/15 mL; liq 150 mg/15 mL; soln 50 mg/mL NOTES: No significant side effects; no laxative action Dolasetron (Anzemet) COMMON USES: Prevention of nausea and vomiting associated with chemotherapy ACTIONS: 5-HT3 receptor antagonists 22 530 Clinician’s Pocket Reference, 9th Edition DOSAGE: Adults & Peds. 1.8 mg/kg IV as a single dose 30 min prior to chemotherapy. Adults. 100 mg PO as a single dose. 1 h prior to chemotherapy. Peds. 1.8 mg/kg PO to max 100 mg as a single dose SUPPLIED: Tabs 50, 100 mg; Inj 20 mg/mL NOTES: May prolong QT interval Dopamine (Intropin, Dopastat) Used for emergency cardiac care (see Chapter 21) COMMON USES: Short-term use in cardiac decompensation secondary to decreased contractility; increases organ perfusion ACTIONS: Positive inotropic agent with dose-related response. 2–10 µg/kg/min β-effects (increases cardiac output and renal perfusion). 10–20 µg/kg/min α-effects (peripheral vasoconstriction, pres- sor). >20 µg/kg/min peripheral and renal vasoconstriction DOSAGE: Adults & Peds. 5 µg/kg/min by cont inf, ↑ increments of 5 µg/kg/min to a max of 50 µg/kg/min based on effect SUPPLIED: Inj 40, 80, 160 mg/mL NOTES: Dosage >10 µg/kg/min may ↓ renal perfusion; monitor urinary output; monitor ECG for ↑ in heart rate, BP, and ectopic activity; monitor PCWP and cardiac output if possible. (See also Table 20–10, page 637.) Dornase Alfa (Pulmozyme) COMMON USES: ↓ Frequency of respiratory infections in patients with CF ACTIONS: Enzyme that selectively cleaves DNA DOSAGE: Inhal 2.5 mg/d SUPPLIED: Soln for inhalation 1 mg/mL NOTES: Use with recommended nebulizer Dorzolamide (Trusopt) COMMON USES: Glaucoma ACTIONS: Carbonic anhydrase inhibitor DOSAGE: 1 gtt in eye(s) tid SUPPLIED: 2% soln Dorzolamide and Timolol (Cosopt) COMMON USES: Glaucoma ACTIONS: Carbonic anhydrase inhibitor with β-adreneric blocker DOSAGE: 1 gtt in eye(s) bid SUPPLIED: Soln dorzolamide 2% and timolol 0.5% Doxazosin (Cardura) COMMON USES: HTN and BPH ACTIONS: α1-Adrenergic blocker; relaxation of bladder neck smooth muscle fibers DOSAGE: HTN: Initially 1 mg/d PO; may be ↑ to 16 mg/d PO. BPH: Initially 1 mg/d PO, may be ↑ to 8 mg/d PO SUPPLIED: Tabs 1, 2, 4, 8 mg NOTES: Doses >4 mg ↑ likelihood of excessive postural hypotension, asthenia, retrograde ejaculation Doxepin (Sinequan, Adapin) COMMON USES: Depression, anxiety, and chronic pain ACTIONS: Tricyclic antidepressant; increases the synaptic concentrations of serotonin or norepi- nephrine in CNS DOSAGE: 25–150 mg/d PO, usually hs, but can be in ÷ doses SUPPLIED: Caps 10, 25, 50, 75, 100, 150 mg; oral conc 10 mg/mL NOTES: Anticholinergic, CNS, and cardiovascular side effects 22 22 Commonly Used Medications 531 Doxepin Topical (Zonalon) COMMON USES: Short-term Rx pruritus (atopic dermatitis or lichen simplex chronicus) ACTIONS: Tricyclic antidepressant; increases synaptic concentrations of serotonin or norepineph- rine DOSAGE: Apply thin coating qid for max 8 d SUPPLIED: 5% cream NOTES: Apply to limited areas to avoid systemic toxicity (anticholinergic, CNS, and cardiovascular side effects) Doxorubicin (Adriamycin, Rubex) COMMON USES: Acute leukemias; Hodgkin’s and non-Hodgkin’s lymphomas; breast cancer; soft tissue and osteosarcomas; Ewing’s sarcoma; Wilms’ tumor; neuroblastoma; bladder, ovarian, gas- tric, thyroid, and lung cancers ACTIONS: DNA intercalating agent; inhibitor

of DNA topoisomerases I and II DOSAGE: 60–75 mg/m2 q 3 wk; reduced cardiotoxicity with weekly (20 mg/m2/wk) or cont inf (60–90 mg/m2 over 96 h) schedules. (Refer to specific protocols) SUPPLIED: Inj 10, 20, 50, 75, 200 mg NOTES: Toxicity symptoms: Myelosuppression; extravasation leads to tissue damage; venous streaking and phlebitis, nausea and vomiting, diarrhea, mucositis, and radiation recall phenomenon. Cardiomyopathy rare but dose-related; limit of 550 mg/m2 cumulative dose (400 mg/m2 if prior his- tory of mediastinal irradiation) Doxycycline (Vibramycin) COMMON USES: Broad-spectrum antibiotic, including activity against Rickettsia spp., Chlamydia, and M. pneumoniae ACTIONS: Tetracycline; interferes with protein synthesis DOSAGE: Adults. 100 mg PO q12h on 1st day, then 100 mg PO qd–bid or 100 mg IV q12h. Peds >8 y. 5 mg/kg/24h PO, to a max of 200 mg/d ÷ qd–bid SUPPLIED: Tabs 50, 100 mg; caps 20, 50, 100 mg; syrup 50 mg/5 mL; susp 25 mg/5 mL; inj 100, 200 mg/vial NOTES: Useful for chronic bronchitis; tetracycline of choice for patients with renal impairment Dronabinol (Marinol) [C] COMMON USES: Nausea and vomiting; appetite stimulation ACTIONS: Antiemetic; inhibits the vomiting center in the medulla DOSAGE: Adults & Peds. Antiemetic: 5–15 mg/m2/dose q4–6h PRN. Adults. Appetite: 2.5 mg PO before lunch and dinner SUPPLIED: Caps 2.5, 5, 10 mg NOTES: Principal psychoactive substance present in marijuana; many CNS side effects Droperidol (Inapsine) COMMON USES: Nausea and vomiting; premedication for anesthesia ACTIONS: Tranquilization, sedation, and antiemetic DOSAGE: Adults. Nausea: 2.5–5 mg IV or IM q3–4h PRN. Premed: 2.5–10 mg IV, 30–60 min preop. Peds. Premed: 0.1–0.15 mg/kg/dose SUPPLIED: Inj 2.5 mg/mL NOTES: Drowsiness, moderate hypotension, and occasional tachycardia Econazole (Spectazole) COMMON USES: Most tinea, cutaneous Candida, and tinea versicolor infections ACTIONS: Topical antifungal DOSAGE: Apply to affected areas bid (qd for tinea versicolor) for 2–4 wk SUPPLIED: Topical cream 1% 22 532 Clinician’s Pocket Reference, 9th Edition NOTES: Relief of symptoms and clinical improvement may be seen early in treatment, but carry out course of therapy to avoid recurrence Echothiophate Iodine (Phospholine Ophthalmic) COMMON USES: Glaucoma ACTIONS: Cholinesterase inhibitor DOSAGE: 1 gtt eye(s) bid with one dose hs SUPPLIED: Powder to reconstitute 1.5 mg/0.03%; 3 mg/0.06%; 6.25 mg/0.125%; 12.5 mg/0.25% Edrophonium (Tensilon) COMMON USES: Diagnosis of MyG; acute myasthenic crisis; curare antagonist ACTIONS: Anticholinesterase DOSAGE: Adults. Test for MyG: 2 mg IV in 1 min; if tolerated, give 8 mg IV; a positive test is a brief increase in strength. Peds. Test for MyG: Total dose of 0.2 mg/kg. Give 0.04 mg/kg as a test dose. If no reaction occurs, give the remainder of the dose in 1-mg increments to max of 10 mg SUPPLIED: Inj 10 mg/mL NOTES: Can cause severe cholinergic effects; keep atropine available Efavirenz (Sustiva) COMMON USES: HIV infections ACTIONS: Antiretroviral agent, nonnucleoside reverse transcriptase inhibitor DOSAGE: Adults. 600 mg/d PO. Peds. Refer to product information for dosing chart SUPPLIED: Caps 50, 100, 200 mg NOTES: Take hs, may cause somnolence, vivid dreams, dizziness; may cause rash Enalapril (Vasotec) COMMON USES: HTN, CHF, and asymptomatic LVD ACTIONS: ACE inhibitor DOSAGE: Adults. 2.5–5 mg/d PO ↑ by effect to 10–40 mg/d as 1–2 ÷ doses, or 1.25 mg IV q6h. Peds. 0.05–0.08 mg/kg/dose PO q12–24h SUPPLIED: Tabs 2.5, 5, 10, 20 mg; inj 1.25 mg/mL NOTES: Initial dose can produce symptomatic hypotension, especially with concomitant diuretics; discontinue diuretic for 2–3 d prior to initiation if possible; monitor closely for ↑ in serum potas- sium; may cause a nonproductive cough Enoxaparin (Lovenox) COMMON USES: Prevention and Rx of DVT; Rx PE; unstable angina and non-Q-wave MI ACTIONS: Low-molecular-weight heparin DOSAGE: Prevention: 30 mg bid SC or 40 mg SC q24h. DVT/PE: 1 mg/kg SC q12h or 1.5 mg/kg SC q24h. Angina: 1 mg/kg SC q12h SUPPLIED: Inj 10 mg/0.1 mL (30-, 40-, 60-, 80-, 100-mg syringes) NOTES: Does not significantly affect bleeding time, platelet function, PT, or APTT Entacapone (Comtan) COMMON USES: Parkinson’s disease ACTION: Selective and reversible inhibitor of COMT DOSAGE: 200 mg administered concurrently with each levodopa/carbidopa dose to a max of 8×/d SUPPLIED: Tabs 200 mg Ephedrine COMMON USES: Acute bronchospasm, nasal congestion, hypotension, narcolepsy, enuresis, and MyG 22 ACTIONS: Sympathomimetic that stimulates both α- and β-receptors 22 Commonly Used Medications 533 DOSAGE: Adults. 25–50 mg IM or IV q 10 min to a max of 150 mg/d or 25–50 mg PO q3–4h PRN. Peds. 0.2–0.3 mg/kg/dose IM or IV q4–6h PRN SUPPLIED: Inj 25, 50 mg/mL; caps 25, 50 mg; syrup 11, 20 mg/5 mL Epinephrine (Adrenalin, Sus-Phrine, others) Used for emergency cardiac care (see Chapter 21) COMMON USES: Cardiac arrest, anaphylactic reactions, and acute asthma ACTIONS: β-Adrenergic agonist with some α-effects DOSAGE: Adults. Emergency cardiac care: 0.5–1.0 mg (5–10 mL of 1:10,000) IV q 5 min to re- sponse. Anaphylaxis: 0.3–0.5 mL of 1:1000 dilution SC; may repeat q 10–15 min to a max of 1 mg/dose and 5 mg/d. Asthma: 0.3–0.5 mL of 1:1000 dilution SC, repeated at 20-min–4-h inter- vals or 1 inhal (met-dose) repeated in 1–2 min or susp 0.1–0.3 mL SC for extended effect. Peds. Emergency cardiac care: 0.1 mL/kg of 1:10,000 dilution IV q 3–5 min to response SUPPLIED: Inj 1:1000, 1:2000, 1:10,000, 1:100,000; susp for inj 1:200; aerosol; soln for inhal NOTES: Sus-Phrine offers sustained action. In acute cardiac settings, can be given via endotracheal tube if central line not available Epoetin Alfa [Erythropoietin] (Epogen, Procrit) COMMON USES: Anemia associated with CRF, zidovudine treatment in HIV-infected patients, and patients receiving cancer chemotherapy; reduction in transfusions associated with surgery ACTIONS: Erythropoietin supplementation DOSAGE: Adults & Peds. 50–150 U/kg 3×/wk; adjust the dose q 4–6 wk as needed. Surgery: 300 U/kg/d for 10 d prior to surgery SUPPLIED: Inj 2000, 3000, 4000, 10,000, 20,000 U/mL NOTES: May cause HTN, headache, tachycardia, nausea, and vomiting; store in refrigerator Epoprostenol (Flolan) COMMON USES: Pulmonary HTN ACTIONS: Dilates the pulmonary and systemic arterial vascular beds; inhibits platelet aggregation DOSAGE: 4 ng/kg/min IV cont inf; make dosage adjustments based on clinical status and package insert guidelines SUPPLIED: Inj 0.5, 1.5 mg NOTES: Availability through PBM Eprosartan (Teveten) COMMON USES: HTN ACTIONS: Angiotensin II receptor antagonist DOSAGE: 400–800 mg/d as single dose or bid SUPPLIED: Tabs 400, 600 mg NOTES: Avoid use during PRG Eptifibatide (Integrilin) COMMON USES: Acute coronary syndrome ACTIONS: Glycoprotein IIb/IIIa inhibitor DOSAGE: 180 µg/kg IV bolus, followed by 2 µg/kg/min cont inf SUPPLIED: Inj 0.75, 2 mg/mL Erythromycin (E-mycin, Ilosone, Erythrocin, others) COMMON USES: Infections caused by group A streptococci (S. pyrogenes), α-hemolytic strepto- cocci, and Neisseria gonorrhoeae infections in penicillin-allergic patients, S. pneumoniae, M. pneumoniae, and Legionella infections ACTIONS: Bacteriostatic; interferes with protein synthesis DOSAGE: Adults. 250–500 mg PO qid or 500 mg–1 g IV qid. Peds. 30–50 mg/kg/24h PO or IV ÷ q6h, to a max of 2 g/d 22 534 Clinician’s Pocket Reference, 9th Edition SUPPLIED: Powder for inj as lactobionate and gluceptate salts: 500 mg, 1 g; Base: Tabs 250, 333, 500 mg; caps 250 mg; Estolate: Tabs 500 mg; caps 250 mg; susp 125, 250 mg per 5 mL; Stearate: Tabs 250, 500 mg; Ethylsuccinate: Chewable tabs 200 mg; tabs 400 mg; susp 200, 400 mg/5 mL NOTES: Frequent mild GI disturbances; estolate salt associated with cholestatic jaundice; ery- thromycin base not well absorbed from the GI tract; some forms better tolerated with respect to GI irritation; lactobionate salt contains benzyl alcohol, so use with caution in neonates; used as part of the Condon bowel prep Erythromycin and Benzoyl Peroxide (Benzamycin) COMMON USES: Topical control of acne vulgaris ACTIONS: Macrolide antibiotic with keratolytic DOSAGE: Apply bid (AM & PM) SUPPLIED: Gel erythromycin 30 mg/benzoyl peroxide 50 mg/g Erythromycin and Sulfisoxazole (Eryzole, Pediazole) COMMON USES: Bacterial infections of the upper and lower respiratory tract; otitis media in chil- dren due to H. influenzae; other infections in penicillin-allergic patients ACTIONS: Macrolide antibiotic with sulfonamide DOSAGE: Based on erythromycin content. Adults. 400 mg erythromycin/1200 mg sulfisoxazole PO q6h. Peds >2 mo. 40–50 mg/kg/d of erythromycin PO ÷ tid–qid; max 2 g erythromycin or 6 g sul- fisoxazole/d or estimated dose of 1.25 mL/kg/d ÷ tid–qid SUPPLIED: Susp erythromycin ethylsuccinate 200 mg/sulfisoxazole 600 mg/5 mL Erythromycin, Ophthalmic (Ilotycin Ophthalmic) COMMON USES: Conjunctival infections ACTIONS: Macrolide antibiotic DOSAGE: Apply q6h SUPPLIED: 0.5% Oint Erythromycin, Topical (Akne-Mycin Topical, Del-Mycin Topical, Emgel Topical, Staticin Topical, others) COMMON USES: Acne ACTIONS: Macrolide antibiotic DOSAGE: Wash and dry area, apply 2% product over area bid SUPPLIED: Soln 1.5, 2%;gel; impregnated pads and swabs 2% Esmolol (Brevibloc) Used for emergency cardiac care (see Chapter 21) COMMON USES: SVT and noncompensatory sinus tachycardia ACTIONS: β-Adrenergic blocking agent; class II antiarrhythmic DOSAGE: Adults & Peds. Initiate treatment with 500 µg/kg load over 1 min, then 50 µg/kg/min for 4 min; if inadequate response, repeat the loading dose and follow with maintenance infusion of 100 µg/kg/min for 4 min; continue the titration process by repeating the loading dose followed by in- cremental ↑ in the maintenance dose of 50 µg/kg/min for 4 min until the desired heart rate is reached or BP decreases ; average dose 100 µg/kg/min SUPPLIED: Inj 10, 250 mg/mL NOTES: Monitor closely for hypotension; ↓ or discontinuing infusion reverses hypotension in ≅30 min Estazolam (Prosom) [C] COMMON USES: Insomnia ACTIONS: Benzodiazepine DOSAGE: 1–2 mg PO hs PRN 22 SUPPLIED: Tabs 1, 2 mg 22 Commonly Used Medications 535 Esterified Estrogens (Estratab, Menest) COMMON USES: Vasomotor symptoms, atrophic vaginitis, or kraurosis vulvae associated with menopause; female hypogonadism ACTIONS: Estrogen supplementation DOSAGE: Menopause: 0.3–1.25 mg/d, administered cyclically 3 wk on and 1 wk off. Hypogo- nadism: 2.5 mg PO qd–tid SUPPLIED: Tabs 0.3, 0.625, 1.25, 2.5 mg Esterified Estrogens + Methyltestosterone (Estratest) COMMON USES: Moderate to severe vasomotor symptoms associated with menopause; postpartum breast engorgement ACTIONS: Estrogen and androgen supplementation DOSAGE: 1 tab/d for 3 wk, then 1 wk off SUPPLIED: Tabs (estrogen/methyltestosterone) 0.625 mg/1.25 mg, 1.25 mg/2.5 mg Estradiol, (Estrace) COMMON USES: Atrophic vaginitis and kraurosis vulvae associated with menopause, vasomotor symptoms ACTIONS: Estrogen supplementation DOSAGE: Oral: 1–2 mg/d, adjust dose as necessary to control symptoms. Vaginal cream: 2–4 g/d for 2 wk, then 1 g 1–3×/wk SUPPLIED: Tabs 0.5, 1, 2 mg; vaginal cream Estradiol, Transdermal (Estraderm, others) COMMON USES: Severe vasomotor symptoms associated with menopause; female hypogonadism ACTIONS: Estrogen supplementation DOSAGE: 0.1 mg/d patch 1–2×/wk depending on product; adjust dose as necessary to control symp- toms SUPPLIED: TD patches (delivers mg/24h) 0.025, 0.0375, 0.05, 0.075, 0.1 Estramustine Phosphate (Estracyte, Emcyt) COMMON USES: Advanced prostate cancer ACTIONS: Antimicrotubule agent; weak estrogenic and antiandrogenic activity DOSAGE: 14 mg/kg/d in 3–4 ÷ doses SUPPLIED: Caps 140 mg NOTES: Toxicity symptoms: Nausea and vomiting, exacerbation of preexisting CHF, gynecomastia in 20–100% Estrogen, Conjugated (Premarin) COMMON USES: Moderate to severe vasomotor symptoms associated with menopause; atrophic vaginitis; palliative therapy of advanced prostatic carcinoma; prevention of estrogen deficiency-in- duced osteoporosis ACTIONS: Hormonal replacement DOSAGE: 0.3–1.25 mg/d PO cyclically; prostatic carcinoma requires 1.25–2.5 mg PO tid SUPPLIED: Tabs 0.3, 0.625, 0.9, 1.25, 2.5 mg; inj 25 mg/mL NOTES: Do NOT use in PRG; associated with an increased risk of endometrial carcinoma, gallblad- der disease, thromboembolism, and possibly breast cancer; generic products not equivalent Estrogen, Conjugated + Methylprogesterone (Premarin + Methylprogesterone) COMMON USES: Vasomotor symptoms associated with menopause ACTIONS: Estrogen and androgen combination DOSAGE: 1 tab/d SUPPLIED: Tabs containing 0.625 mg of estrogen, conjugated, and 5 mg of methylprogesterone 22 536 Clinician’s Pocket Reference, 9th Edition Estrogen, Conjugated + Methyltestosterone (Premarin + Methyltestosterone) COMMON USES: Moderate to severe vasomotor symptoms associated with menopause; postpartum breast engorgement ACTIONS: Estrogen and androgen combination DOSAGE: 1 tab/d for 3 wk, then 1 wk off SUPPLIED: Tabs (estrogen/methyltestosterone) 0.625 mg/5 mg, 1.25 mg/10 mg Ethacrynic Acid (Edecrin) COMMON USES: Edema, CHF, and ascites; any time rapid diuresis is desired ACTIONS: Loop diuretic; inhibits reabsorption of sodium and chlorine in the ascending loop of Henle and the distal renal tubule DOSAGE: Adults. 50–200 mg PO qd or 50 mg IV PRN. Peds. 1 mg/kg/dose IV. Repeated doses NOT recommended SUPPLIED: Tabs 25, 50 mg; powder for inj 50 mg NOTES: Contra in anuria; severe side effects reported Ethambutol (Myambutol) COMMON USES: Pulmonary TB and other mycobacterial infections ACTIONS: Inhibits cellular metabolism DOSAGE: Adults & Peds >12 y. 15–25 mg/kg/d PO as a single dose SUPPLIED: Tabs 100, 400 mg NOTES: May cause vision changes and GI upset Ethinyl Estradiol (Estinyl, Feminone) COMMON

USES: Vasomotor symptoms associated with menopause; female hypogonadism ACTIONS: Estrogen supplementation DOSAGE: 0.02–1.5 mg/d ÷ qd–tid SUPPLIED: Tabs 0.02, 0.05, 0.5 mg Ethosuximide (Zarontin) COMMON USES: Seizures ACTIONS: Anticonvulsant; increases the seizure threshold DOSAGE: Adults. Initially, 500 mg PO ÷ bid; ↑ by 250 mg/d q 4–7 d PRN (max 1500 mg/d) Peds. 20–40 mg/kg/24h PO ÷ bid to a max of 1500 mg/d SUPPLIED: Caps 250 mg; syrup 250 mg/5 mL NOTES: Blood dyscrasias as well as CNS and GI side effects may occur; use caution in renal or he- patic impairment. (See Table 27–7, pages 631–634, for levels.) Etidronate Disodium (Didronel) COMMON USES: Hypercalcemia of malignancy and hypertropic ossification ACTIONS: Inhibition of normal and abnormal bone resorption DOSAGE: 5–20 mg/kg/d, may be given in ÷ doses. (Duration of therapy 3–6 mo) 7.5 mg/kg/d IV in- fusion over 2 h SUPPLIED: Tabs 200, 400 mg; inj 50 mg/mL NOTES: GI intolerance may be ↓ by ÷ oral daily doses Etodolac (Lodine) COMMON USES: Arthritis and pain ACTIONS: NSAID DOSAGE: 200–400 mg PO bid–qid (max 1200 mg/d) SUPPLIED: Tabs 400, 500 mg; ER tabs 400, 500, 600 mg; caps 200, 300 mg 22 22 Commonly Used Medications 537 Etoposide [VP-16] (Vepesid) COMMON USES: Testicular cancer, non-small-cell lung cancers, Hodgkin’s and non-Hodgkin’s lymphomas, pediatric ALL, and allogeneic and autologous BMT in high doses ACTIONS: Topoisomerase II inhibitor DOSAGE: 50 mg/m2/d IV for 3–5 d; 50 mg/m2/d PO for 21 d (bioavailability of the oral formulation ≈50% of the IV form); 2–6 g/m2 or 25–70 mg/kg used in BMT. (Refer to specific protocols) SUPPLIED: Caps 50 mg; inj 20 mg/mL NOTES: Toxicity symptoms: Myelosuppression, nausea and vomiting, and alopecia; hypotension may occur if infused too rapidly; anaphylaxis or lesser hypersensitivity reactions (wheezing) rare; potential for secondary leukemias Famciclovir (Famvir) COMMON USES: Acute herpes zoster (shingles) and genital herpes infections ACTIONS: Inhibits viral DNA synthesis DOSAGE: Zoster: 500 mg PO q8h. Simplex: 125–250 mg PO bid SUPPLIED: Tabs 125, 250, 500 mg Famotidine (Pepcid) COMMON USES: Short-term Rx of active duodenal ulcer and benign gastric ulcer; maintenance therapy for duodenal ulcer, hypersecretory conditions, GERD, and heartburn ACTIONS: H2-antagonist; inhibits gastric acid secretion DOSAGE: Adults. Ulcer: 20–40 mg PO hs or 20 mg IV q12h. Hypersecretion: 20–160 mg PO q6h. GERD: 20 mg PO bid; maintenance 20 mg PO hs. Heartburn: 10 mg PO PRN heartburn; Peds. 1–2 mg/kg/d SUPPLIED: Tabs 10, 20, 40 mg; chewable tabs 10 mg; susp 40 mg/5 mL; inj 10 mg/mL NOTES: ↓ Dose in severe renal insufficiency Felodipine (Plendil) COMMON USES: HTN and CHF ACTIONS: Ca channel-blocker DOSAGE: 5–20 mg PO qd SUPPLIED: ER tabs 2.5, 5, 10 mg NOTES: Closely monitor BP in elderly and in impaired hepatic function; do NOT use doses >10 mg in these patients; bioavailability is ↑ when administered with grapefruit juice Fenofibrate (Tricor) COMMON USES: Hypertriglyceridemia ACTIONS: Inhibits triglyceride synthesis DOSAGE: Initially 67 mg/d, ↑ to 67 mg tid or 200 mg/d SUPPLIED: Caps 67, 200 mg NOTES: Take with meals to increase bioavailability; May cause cholecystitis; monitor LFTs Fenoldopam (Corlopam) COMMON USES: Hypertensive emergency ACTIONS: Rapid acting vasodilator DOSAGE: Initial dose 0.03–0.1 µg/kg/min IV cont inf, titrate to effect q 15 min with 0.05–0.1 µg/kg/min increments SUPPLIED: Inj 10 mg/mL NOTES: Avoid concurrent use with β-blockers Fenoprofen (Nalfon) COMMON USES: Arthritis and pain ACTIONS: NSAID 22 538 Clinician’s Pocket Reference, 9th Edition DOSAGE: 200–600 mg q4–8h, to a max of 3200 mg/d SUPPLIED: Caps 200, 300 mg; tabs 600 mg Fentanyl (Sublimaze) [C-II] COMMON USES: Short-acting analgesic used in conjunction with anesthesia ACTIONS: Narcotic DOSAGE: Adults & Peds. 0.025–0.15 mg/kg IV/IM titrated to effect SUPPLIED: Inj 0.05 mg/mL NOTES: Causes significant sedation; 0.1 mg of fentanyl = 10 mg of morphine IM Fentanyl, Transdermal (Duragesic) [C-II] COMMON USES: Chronic pain ACTIONS: Narcotic DOSAGE: Apply a patch to the upper torso q72h. Dose calculated from the narcotic requirements for the previous 24 h SUPPLIED: TD patches deliver 25, 50, 75, 100 µg/h NOTES: 0.1 mg of fentanyl = 10 mg of morphine IM Fentanyl, Transmucosal System (Actiq, Fentanyl Oralet) [C-II] COMMON USES: Induction of anesthesia and breakthrough cancer pain ACTIONS: Narcotic DOSAGE: Adults & Peds. Anesthesia: 5–15 µg/kg. Pain: 200 µg consumed over 15 min, titrate to appropriate effect SUPPLIED: Lozenges 100, 200, 300, 400 µg; lozenges on stick 200, 400, 600, 800, 1200, 1600 µg Ferric Gluconate Complex (Ferrlecit) COMMON USES: Iron deficiency in patients receiving supplemental erythropoietin therapy ACTIONS: Supplemental iron DOSAGE: Give test dose of 2 mL (25 mg Fe) infused over 1 h. If no reaction, 125 mg (10 mL) IV over 1 h until favorable hematocrit achieved. Usual cumulative dose 1 g Fe administered over 8 ses- sions SUPPLIED: Inj 12.5 mg/mL Fe NOTES: Dosage is expressed as mg Fe; may be infused during dialysis Ferrous Gluconate (Fergon, others) COMMON USES: Fe deficiency anemia and Fe supplementation ACTIONS: Dietary supplementation DOSAGE: Adults. 100–200 mg Fe/d SUPPLIED: Tabs 240 (27 mg Fe), 325 mg (36 mg Fe) NOTES: 12% Fe; may turn stool and urine dark Ferrous Sulfate COMMON USES: Fe deficiency anemia and Fe supplementation ACTIONS: Dietary supplementation DOSAGE: Adults. 300 mg PO bid–tid. Peds. 1–4 mg/kg/24h ÷ qd–bid SUPPLIED: Tabs 187, 200, 324 mg; SR caplets and tabs 160 mg; gtt 75 mg/0.6 mL; elixir 220 mg/5 mL; syrup 90 mg/5 mL NOTES: May turn stools and urine dark; can cause GI upset and constipation; vitamin C taken with ferrous sulfate ↑ absorption of Fe, especially in patients with atrophic gastritis Fexofenadine (Allegra) COMMON USES: Relief of allergic rhinitis ACTIONS: Antihistamine 22 22 Commonly Used Medications 539 DOSAGE: Adults & Peds >12 y. 60 mg bid or 180 mg/d SUPPLIED: Caps 60 mg, 180 mg tabs; also available in combination with pseudoephedrine (60 mg fexoferadine/120 mg pseudoephedrine) Filgrastim [G-CSF] (Neupogen) COMMON USES: Decrease incidence of infection in febrile neutropenic patients, and Rx chronic neutropenia ACTIONS: Recombinant G-CSF DOSAGE: Adults & Peds. 5 µg/kg/d SC or IV as a single daily dose SUPPLIED: Inj 300 µg/mL NOTES: May cause bone pain. Discontinue therapy when ANC >10,000 Finasteride (Proscar, Propecia) COMMON USES: BPH and androgenetic alopecia ACTIONS: Inhibits 5α reductase DOSAGE: BPH: 5 mg/d PO [Proscar]. Alopecia: 1 mg/d PO [Propecia] SUPPLIED: Tabs 1, 5 mg NOTES: Decreases PSA levels; may take 3–6 mo to see effect on urinary symptoms Flavoxate (Urispas) COMMON USES: Symptomatic relief of dysuria, urgency, nocturia, suprapubic pain, urinary fre- quency, and incontinence ACTIONS: Counteracts smooth muscle spasm of the urinary tract DOSAGE: 100–200 mg PO tid–qid SUPPLIED: Tabs 100 mg NOTES: May cause drowsiness, blurred vision, and dry mouth Flecainide (Tambocor) COMMON USES: Prevention of PAF/flutter and PSVT, Rx life-threatening ventricular arrhythmias ACTIONS: Class 1C antiarrhythmic DOSAGE: Adults. 100 mg PO q12h; ↑ in increments of 50 mg q12h q 4 d to a max of 400 mg/d. Peds. 3–6 mg/kg/d in 3 ÷ doses SUPPLIED: Tabs 50, 100, 150 mg NOTES: May cause new or worsened arrhythmias; therapy should be initiated in the hospital; may dose q8h if the patient is intolerant or uncontrolled at 12-h intervals; drug interactions with propra- nolol, digoxin, verapamil, and disopyramide; may cause CHF Floxuridine (FUDR) COMMON USES: Colon carcinoma, pancreatic carcinoma, liver cancer, biliary tract cancers, and adenocarcinoma of the GI tract metastatic to the liver ACTIONS: Inhibitor of thymidylate synthase; interferes with DNA synthesis (S phase-specific) DOSAGE: 0.1–0.6 mg/kg/d for 1–6 wk SUPPLIED: Inj 500 mg NOTES: Toxicity symptoms: Myelosuppression, nausea and vomiting, anorexia, abdominal cramps, diarrhea, mucositis, alopecia, skin rash, and hyperpigmentation; rare neurotoxicity (blurred vision, depression, nystagmus, vertigo, and lethargy). Intraarterial catheter-related problems (ischemia, thrombosis, bleeding, and infection) Fluconazole (Diflucan) COMMON USES: Oropharyngeal and esophageal candidiasis; cryptococcal meningitis; Candida in- fections of the lungs, peritoneum, and urinary tract; prevention of candidiasis in BMT patients on chemotherapy or radiation; and candidal vaginitis ACTIONS: Antifungal; inhibits fungal cytochrome P-450 sterol demethylation 22 540 Clinician’s Pocket Reference, 9th Edition DOSAGE: Adults. 100–400 mg/d PO or IV. Vaginitis: 150 mg PO as a single dose. Peds. 3–6 mg/kg/d PO or IV SUPPLIED: Tabs 50, 100, 150, 200 mg; susp 10, 40 mg/mL; inj 2 mg/mL NOTES: Adjust dose in renal insufficiency; oral dosing produces the same blood levels as IV dos- ing, so use oral route whenever possible Fludarabine Phosphate (Fludara) COMMON USES: CLL, low-grade lymphoma, and mycosis fungoides ACTIONS: Inhibits ribonucleotide reductase; blocks DNA polymerase-induced DNA repair DOSAGE: 18–30 mg/m2/d for 5 d, given as a 30-min inf (Refer to specific protocols) SUPPLIED: Inj 50 mg NOTES: Toxicity symptoms: Myelosuppression, nausea and vomiting, diarrhea, and hepatic trans- aminase elevations; severe CNS toxicity rare in leukemic patients and pulmonary toxicity Fludrocortisone Acetate (Florinef) COMMON USES: Partial treatment for adrenocortical insufficiency ACTIONS: Mineralocorticoid replacement DOSAGE: Adults. 0.05–0.2 mg/d PO. Peds. 0.05–0.1 mg/d PO SUPPLIED: Tabs 0.1 mg NOTES: For adrenal insufficiency, must be used in conjunction with a glucocorticoid supplement; dosage changes based on plasma renin activity Flumazenil (Romazicon) Used for emergency (see Chapter 21) COMMON USES: For complete or partial reversal of the sedative effects of benzodiazepines (di- azepam, etc) ACTIONS: Benzodiazepine receptor antagonist DOSAGE: Adults. 0.2 mg IV over 15 s; dose may be repeated if the desired level of consciousness is not obtained, to a max dose of 1 mg. Peds. 0.01 mg/kg to a max of 0.2 mg IV over 15 s. Repeat doses 0.005 mg/kg at 1-min intervals SUPPLIED: Inj 0.1 mg/mL NOTES: Does NOT reverse narcotics Flunisolide (Aerobid, Nasalide) COMMON USES: Control of bronchial asthma in patients requiring chronic corticosteroid therapy; relief of seasonal or perennial allergic rhinitis ACTIONS: Topical steroid DOSAGE: Adults. 2–4 inhal bid. Nasal: 2 sprays/nostril bid. Peds >6 y. 2 inhal bid. Nasal: 1–2 sprays/nostril bid SUPPLIED: Met-dose aerosol 250 mg; nasal spray 0.025% NOTES: May cause oral candidiasis; NOT for acute asthma attack Fluorouracil [5-FU] (Adrucil) COMMON USES: Colorectal, bladder, gastric, pancreatic, anal, head and neck, and breast cancers; topical application for basal cell carcinoma of the skin ACTIONS: Inhibitor of thymidylate synthetase (interferes with DNA synthesis, S phase-specific) DOSAGE: 370–1000 mg/m2/d for 1–5 d; intravenously as IV push to 24-h cont inf; protracted ve- nous infusion of 200–300 mg/m2/d. (See specific protocols.) SUPPLIED: Inj 50 mg/mL NOTES: Toxicity symptoms: Stomatitis, esophagopharyngitis, diarrhea, anorexia, and nausea and vomiting. Myelosuppression (leukocytopenia, thrombocytopenia, and anemia); rash, dry skin, and photosensitivity frequent. Tingling in the hands and feet followed by pain (palmar-plantar 22 erythrodysesthesia); phlebitis and discoloration at inj sites 22 Commonly Used Medications 541 Fluorouracil, Topical [5-FU] (Efudex) COMMON USES: Basal cell carcinoma of the skin, actinic and solar keratosis ACTIONS: Inhibitor of thymidylate synthetase (interferes with DNA synthesis, S phase-specific) DOSAGE: Apply 5% cream bid for 4–6 wk SUPPLIED: Cream 1, 5%; soln 1, 2, 5% NOTES: Toxicity symptoms: Rash, dry skin, and photosensitivity Fluoxetine (Prozac, Sarafem) COMMON USES: Depression, OCD, bulimia, PMDD ACTIONS: SSRI DOSAGE: Initially, 20 mg/d PO; ↑to a max of 80 mg/24h; ÷ doses of >20 mg/d. Bulimia: 60 mg/d in AM. PMDD: 20 mg/d SUPPLIED: Caps 10, 20 mg; tabs 10 mg; soln 20 mg/5 mL NOTES: May cause nausea, nervousness, and weight loss; hepatic failure dosage adjustment Fluoxymesterone (Halotestin) COMMON USES: Androgen-responsive metastatic breast cancer ACTIONS: Inhibition of secretion of LH and FSH by feedback inhibition DOSAGE: 10–40 mg/d SUPPLIED: Tabs 2, 5, 10 mg NOTES: Toxicity symptoms: Virilization, amenorrhea and menstrual irregularities, hirsutism, alope- cia and acne, nausea, and cholestasis. Hematologic toxicity symptoms: Suppression of clotting fac- tors II, V, VII, and X and polycythemia. ↑ libido, headache, and anxiety Fluphenazine (Prolixin, Permitil) COMMON USES: Psychotic disorders ACTIONS: Phenothiazine antipsychotic; blocks postsynaptic mesolimbic dopaminergic receptors in the brain DOSAGE: 0.5–10 mg/d in ÷ doses PO q6–8h; average maintenance 5.0 mg/d or 1.25 mg IM ini- tially, then 2.5–10 mg/d in ÷ doses q6–8h PRN SUPPLIED: Tabs 1, 2.5, 5, 10; conc 5 mg/mL; elixir 2.5 mg/5 mL; inj 2.5 mg/mL; depot inj 25 mg/mL NOTES: ↓ Dose in elderly; monitor LFT; may cause drowsiness; do NOT administer conc with caf- feine, tannic acid, or pectin-containing products Flurazepam (Dalmane) [C] COMMON USES: Insomnia ACTIONS: Benzodiazepine DOSAGE: Adults & Peds >15 y. 15–30 mg PO hs PRN SUPPLIED: Caps 15, 30 mg NOTES: ↓ Dose in elderly Flurbiprofen (Ansaid) COMMON USES: Arthritis ACTIONS: NSAID DOSAGE: 50–100 mg bid–qid, to a max of 300 mg/d SUPPLIED: Tabs 50, 100 mg Flutamide (Eulexin)

COMMON USES: Advanced prostate cancer (in combination with GnRH agonists, eg, leuprolide or goserelin) with or without radiation for localized prostate cancer ACTIONS: Nonsteroidal antiandrogen DOSAGE: 250 mg PO tid (750 mg total) SUPPLIED: Caps 125 mg 22 542 Clinician’s Pocket Reference, 9th Edition NOTES: Toxicity symptoms: Hot flashes, loss of libido, impotence, diarrhea, nausea and vomiting, and gynecomastia; follow LFT Fluticasone Nasal (Flonase) COMMON USES: Seasonal allergic rhinitis ACTIONS: Topical steroid DOSAGE: Adults & adolescents. 100–250 µg bid. Nasal: 1–2 sprays/nostril/d. Peds 4–11 y. 50 µg bid. Nasal: 1–2 sprays/nostril/d SUPPLIED: Nasal spray 50 µg/actuation Fluticasone Oral (Flovent, Flovent Rotadisk) COMMON USES: Chronic treatment of asthma ACTIONS: Topical steroid DOSAGE: Adults & adolescents. 2–4 puffs bid. Peds 4–11 y. 50 µg bid SUPPLIED: Multidose inhaler 44, 110, or 220 µg/activation; Rotadisk dry powder 50, 100, and 250 µg/activation; risk of thrush NOTES: Counsel patients carefully on use of device Fluvastatin (Lescol) COMMON USES: Adjunct to diet in the treatment of elevated total cholesterol ACTIONS: HMG-CoA reductase inhibitor DOSAGE: 20–40 mg PO hs, may be ↑ to 80 mg/d SUPPLIED: Caps 20, 40 mg NOTES: Avoid concurrent use with gemfibrozil Fluvoxamine (Luvox) COMMON USES: OCD ACTIONS: SSRI DOSAGE: Initial 50 mg as single hs dose, may be ↑ to 300 mg/d in ÷ doses SUPPLIED: Tabs 25, 50, 100 mg NOTES: ÷ doses of >100 mg; numerous drug interactions Folic Acid COMMON USES: Megaloblastic anemia ACTIONS: Dietary supplementation DOSAGE: Adults. Supplement: 0.4 mg/d PO. PRG: 0.8 mg/d PO. Folate deficiency: 1.0 mg PO qd–tid. Peds. Supplement: 0.04–0.4 mg/24h PO, IM, IV, or SC. Folate deficiency: 0.5–1.0 mg/24h PO, IM, IV, or SC SUPPLIED: Tabs 0.1, 0.4, 0.8, 1.0 mg; inj 5 mg/mL NOTES: Recommended for all women of childbearing age; ↓ incidence of fetal neural tube defects by 50% Foscarnet (Foscavir) COMMON USES: CMV; acyclovir-resistant herpes infections ACTIONS: Inhibits viral DNA polymerase and reverse transcriptase DOSAGE: Induction: 60 mg/kg IV q8h for 14–21 d. Maintenance: 90–120 mg/kg/d IV (Monday–Friday) SUPPLIED: Inj 24 mg/mL NOTES: Dosage must be adjusted for renal function; nephrotoxic; monitor ionized calcium closely (causes electrolyte abnormalities); administer through a central line Fosfomycin (Monurol) COMMON USES: Uncomplicated UTI 22 ACTIONS: Inhibits bacterial cell wall synthesis 22 Commonly Used Medications 543 DOSAGE: 3 g PO dissolved in 90–120 mL of water as single dose SUPPLIED: Granule packets 3 g NOTES: May take 2–3 d for symptoms to improve Fosinopril (Monopril) COMMON USES: HTN and heart failure ACTIONS: ACE inhibitor DOSAGE: Initially, 10 mg/d PO; may be ↑ to a max of 80 mg/d PO ÷ qd–bid SUPPLIED: Tabs 10, 20, 40 mg NOTES: ↓ Dose in elderly; may cause nonproductive cough and dizziness Fosphenytoin (Cerebyx) COMMON USES: Status epilepticus ACTION: Inhibits seizure spread in the motor cortex DOSAGE: Dosed as phenytoin equivalents (PE) Loading 15–20 mg PE/kg, maintenance 4–6 mg PE/kg/d SUPPLIED: Inj; 150 mg (= phenytoin 100 mg); 750 mg (= phenytoin 500 mg) NOTES: Requires 15 min to convert the prodrug fosphenytoin to phenytoin; administer at <150 mg PE/min to prevent hypotension; administer with BP monitoring; dosage adjustment/plasma moni- toring may be necessary in hepatic impairment Furosemide (Lasix) Used for emergency cardiac care (see Chapter 21) COMMON USES: Edema, HTN, and CHF ACTIONS: Loop diuretic; inhibits Na and Cl reabsorption in the ascending loop of Henle and the distal renal tubule DOSAGE: Adults. 20–80 mg PO or IV qd–bid. Peds. 1 mg/kg/dose IV q6–12h; 2 mg/kg/dose PO q12h–24h SUPPLIED: Tabs 20, 40, 80 mg; soln 10 mg/mL, 40 mg/5 mL; inj 10 mg/mL NOTES: Monitor for hypokalemia; use with caution in hepatic disease; high doses of the IV form may cause ototoxicity Gabapentin (Neurontin) COMMON USES: Adjunctive therapy in the treatment of partial seizures ACTIONS: Anticonvulsant DOSAGE: 900–1800 mg/d PO in 3 ÷ doses SUPPLIED: Caps 100, 300, 400 mg NOTES: Not necessary to monitor serum gabapentin levels; dosage adjustment in renal impairment Gallium Nitrate (Ganite) COMMON USES: Hypercalcemia of malignancy; bladder cancer ACTIONS: Inhibits resorption of Ca from the bones DOSAGE: Hypercalcemia: 10–200 mg/m2/d for 5 d. Cancer: 350 mg/m2 cont inf for 5 d to 700 mg/m2 rapid IV inf q 2 wk in antineoplastic settings SUPPLIED: Inj 25 mg/mL NOTES: Can cause renal insufficiency; may cause hypocalcemia, hypophosphatemia, and decreased bicarbonate; <1% of patients developed acute optic neuritis; for bladder cancer, use in combination with vinblastine and ifosfamide Ganciclovir (Cytovene, Vitrasert) COMMON USES: Rx and prevention of CMV retinitis and prevention of CMV disease in transplant recipients ACTIONS: Inhibits viral DNA synthesis 22 544 Clinician’s Pocket Reference, 9th Edition DOSAGE: Adults & Peds. IV: 5 mg/kg IV q12h for 14–21 d, then maintenance of 5 mg/kg/d IV for 7 d/wk or 6 mg/kg/d IV for 5 d/wk. Ocular implant: One implant q 5–8 mo. Adults. PO: Following induction, 1000 mg PO tid. Prevention: 1000 mg PO tid SUPPLIED: Caps 250, 500 mg; inj 500 mg; ocular implant 4.5 mg NOTES: NOT a cure for CMV; granulocytopenia and thrombocytopenia are major toxicities; injec- tion should be handled with cytotoxic precautions; take caps with food; implant confers no sys- temic benefit; dosage adjustment in renal impairment Gatifloxacin (Tequin) COMMON USES: Acute exacerbation of chronic bronchitis, sinusitis, community acquired pneumo- nia, UTI ACTIONS: Quinolone antibiotic, inhibits DNA-gyrase DOSAGE: 400 mg/d PO or IV SUPPLIED: Tabs 200, 400 mg; inj NOTES: Avoid use with antacids; do NOT use in children <18 y, pregnant or lactating women; reli- able activity against S. pneumoniae; dosage adjustment in renal impairment Gemcitabine (Gemzar) COMMON USES: Pancreatic cancer, gastric cancer, and lung cancer ACTIONS: Antimetabolite; inhibits ribonucleotide reductase; produces false nucleotide base-inhibit- ing DNA synthesis DOSAGE: 1000 mg/m2 as a 1-h IV inf weekly for 3–4 wk or 6–8 wk SUPPLIED: Inj 20 mg/mL NOTES: Toxicity symptoms: Myelosuppression, nausea and vomiting, diarrhea, drug fever, and skin rash Gemfibrozil (Lopid) COMMON USES: Hypertriglyceridemia, and reduction of CHD risk ACTIONS: Lipid-regulating agent DOSAGE: 1200 mg/d PO in 2 ÷ doses 30 min ac AM and PM SUPPLIED: Tabs 600 mg; caps 300 mg NOTES: Monitor AST, ALT, LDH, alkaline phosphatase, and serum lipids during therapy; cholelithiasis may occur secondary to treatment; may enhance the effect of warfarin; avoid concur- rent use with the HMG-CoA reductase inhibitors Gentamicin (Garamycin, others) COMMON USES: Serious infections caused by susceptible Pseudomonas, Proteus, E. coli, Kleb- siella, Enterobacter, and Serratia, and for initial treatment of gram (−) sepsis ACTIONS: Bactericidal; inhibits protein synthesis DOSAGE: See also Aminoglycoside dosing (page 620). Adults. 3–5 mg/kg/24h IV ÷ q8–24h. Peds. Infants <7 d <1200 g: 2.5 mg/kg/dose q18–24h. >1200 g: 2.5 mg/kg/dose q12–18h. Infants >7 d: 2.5 mg/kg/dose IV q8–12h. Children: 2.5 mg/kg/d IV q8h SUPPLIED: Inj 10, 40 mg/mL, IT preservative-free 2 mg/mL NOTES: Nephrotoxic and ototoxic; ↓ dose with renal insufficiency; monitor CrCl and serum concentration for dosage adjustments (see Table 22–7, pages 631–634). Daily dosing becoming popular Gentamicin, Ophthalmic (Garamycin, Genoptic, Gentacidin, others) COMMON USES: Conjunctival infections ACTIONS: Bactericidal; inhibits protein synthesis DOSAGE: Oint apply bid or tid; soln: 1–2 gtt q2–4h, up to 2 gtt/h for severe infections 22 SUPPLIED: Soln and oint 0.3% 22 Commonly Used Medications 545 Gentamicin, Topical (Garamycin, G-Myticin) COMMON USES: Skin infections caused by susceptible organisms ACTIONS: Bactericidal; inhibits protein synthesis DOSAGE: Adult and Peds >1 y. Apply tid–qid SUPPLIED: Cream; oint; soln 0.3% Gentamicin and Prednisolone, Ophthalmic (Pred-G Ophthalmic) COMMON USES: Steroid-responsive ocular and conjunctival infections sensitive to gentamicin (eg, Staphylococcus, E. coli, H. influenzae, Klebsiella, Neisseria, Pseudomonas, Proteus, and Serratia spp) ACTIONS: Bactericidal; inhibits protein synthesis DOSAGE: Oint apply bid or tid; Soln: 1–2 gtt q2–4h, up to 2 gtt/h for severe infections SUPPLIED: Oint, ophth: Prednisolone acetate 0.6% and gentamicin sulfate 0.3% (3.5 g); Susp, ophth: Prednisolone acetate 1% and gentamicin sulfate 0.3% (2 mL, 5 mL, 10 mL); Soln and oint 0.3% Glimepiride (Amaryl) COMMON USES: Type 2 DM ACTION: Sulfonylurea. Stimulates the release of insulin from the pancreas; increases insulin sensi- tivity at peripheral sites; reduces glucose output from the liver DOSAGE: 1–4 mg/d, up to max of 8 mg SUPPLIED: Tabs 1, 2, 4 mg Glipizide (Glucotrol) COMMON USES: Type 2 DM ACTION: Sulfonylurea. Stimulates the release of insulin from the pancreas; increases insulin sensi- tivity at peripheral sites; reduces glucose output from the liver DOSAGE: 5–15 mg qd–bid SUPPLIED: Tabs 5, 10 mg; ER tabs 5, 10 mg Glucagon Emergency care (see Chapter 21) COMMON USES: Severe hypoglycemic reactions in diabetic patients with sufficient liver glycogen stores or β-blocker overdose ACTIONS: Accelerates liver gluconeogenesis DOSAGE: Adults. 0.5–1.0 mg SC, IM, or IV; repeat after 20 min PRN. β-Blocker overdose: 3–10 mg IV; repeat in 10 min PRN; may be given as cont inf. Peds. Neonates: 0.3 mg/kg/dose SC, IM, or IV q4h PRN. Children: 0.025–0.1 mg/kg/dose SC, IM, or IV; repeat after 20 min PRN SUPPLIED: Inj 1 mg NOTES: Administration of glucose IV necessary; ineffective in states of starvation, adrenal insuffi- ciency, or chronic hypoglycemia Glyburide (Dia
eta, Micronase Glynase Prestab) COMMON USES: Type 2 DM ACTION: Sulfonylurea. Stimulates the release of insulin from the pancreas; increases insulin sensi- tivity at peripheral sites; reduces glucose output from the liver DOSAGE: Nonmicronized: 1.25–10 mg qd–bid. Micronized: 1.5–6 mg qd–bid SUPPLIED: Tabs 1.25, 2.5, 5 mg; micronized tabs [Glynase] 1.5, 3, 4.5, 6 mg NOTES: NOT recommended in renal impairment Glycerin Suppository COMMON USES: Constipation ACTIONS: Hyperosmolar laxative DOSAGE: Adults. 1 adult supp PR PRN. Peds. 1 infant supp PR qd–bid PRN 22 546 Clinician’s Pocket Reference, 9th Edition SUPPLIED: Supp (adult, infant); liq 4 mL/applicatorful Gonadorelin (Lutrepulse) COMMON USES: Primary hypothalamic amenorrhea ACTIONS: Stimulates the pituitary to release the gonadotropins LH and FSH DOSAGE: 5–20 µg IV q 90 min for 21 d using a reservoir and pump SUPPLIED: Inj 0.8 mg, 3.2 mg NOTES: Risk of multiple pregnancies Goserelin (Zoladex) COMMON USES: Advanced prostate cancer and with radiation for localized prostate cancer; en- dometriosis ACTIONS: Slow-release form of LHRH agonist, thereby inhibiting the release of gonadotropin, de- creasing testosterone levels DOSAGE: 3.6 mg SC (implant) q 28 d or 10.8 mg SC q 3 mo SUPPLIED: Subcutaneous implant 3.6, 10.8 mg NOTES: Toxicity symptoms: Hot flashes, ↓ libido, gynecomastia, and transient exacerbation of can- cer-related bone pain (“flare reaction” 7–10 d after 1st dose) Granisetron (Kytril) COMMON USES: Prevention of nausea and vomiting ACTIONS: Serotonin receptor antagonist DOSAGE: Adults & Peds. 10 mg/kg IV 30 min prior to initiation of chemotherapy. Adults. 1 mg PO 1 h prior to chemotherapy, then 12 h later SUPPLIED: Tabs 1 mg; inj 1 mg/mL Guaifenesin (Robitussin, others) COMMON USES: Symptomatic relief of dry, nonproductive cough ACTIONS: Expectorant DOSAGE: Adults. 200–400 mg (10–20 mL) PO q4h. Peds. <2 y: 12 mg/kg/d in 6 ÷ doses. 2–5 y: 50–100 mg (2.5–5 mL) PO q4h. 6–11 y: 100–200 mg (5–10 mL) PO q4h SUPPLIED: Tabs 100, 200, 1200 mg; SR tabs 600 mg; caps 200 mg; SR caps 300 mg; liq 100, 200 mg/5 mL Guaifenesin and Codeine (Robitussin A-C, Brontex, others) [C] COMMON USES: Symptomatic relief of dry, nonproductive cough ACTIONS: Antitussive with expectorant DOSAGE: Adults. 10 mL or 1 tab PO q6–8h. Peds. 2–6 y: 1–1.5 kg/kg codeine/d ÷ dose q4–6h; 6–12 y: 5 mL q4h; >12 y: 10 mL q4h, max 60 mL/24h SUPPLIED: Brontex tab contains 10 mg codeine; Brontex liq 2.5 mg codeine/5 mL; others 10 mg codeine/5 mL Guaifenesin and Dextromethorphan (Many OTC Brands) COMMON USES: Cough due to upper respiratory irritation ACTIONS: Antitussive with expectorant DOSAGE: Adults & Peds >12 y. 10 mL PO q6h. Peds. 2–6 y: 2.5 mL q6–8h, 10 mL/d max; 6–12 y: 5 mL q6–8h, 20 mL max/d Guanabenz (Wytensin) COMMON USES: HTN ACTIONS: Central α-adrenergic agonist DOSAGE: Adults. Initially, 4 mg PO bid; ↑ by 4 mg/d increments at 1–2-wk intervals up to 32 mg bid. Peds >12 y. Initially, 0.5–4 mg/d; ↑ by increments of 0.5–2 mg/d at 1-wk intervals up to 22 24 mg/d ÷ bid 22 Commonly Used Medications 547 SUPPLIED: Tabs 4, 8 mg NOTES: Sedation, dry mouth, dizziness, and headache common Guanadrel (Hylorel) COMMON USES: HTN ACTIONS: Inhibits norepinephrine release from peripheral storage sites DOSAGE: Initially, 5 mg PO bid; ↑ by 10 mg/d increments at 1-wk intervals up to 75 mg PO bid SUPPLIED: Tabs 10, 25 mg NOTES: Interactions with tricyclic antidepressants; lower incidence of orthostatic changes and im- potence than guanethidine;

dosage adjustment in renal impairment Guanethidine (Ismelin) COMMON USES: Moderate to severe HTN or renal HTN ACTIONS: Inhibits release of norepinephrine from peripheral storage sites DOSAGE: Adults. Initially, 10–25 mg PO qd; ↑ the dose based on response. Peds. Initially, 0.2 mg/kg/24h PO; ↑ by 0.2 mg/kg/24h increments q 7–10 d to a max of 3 mg/kg/24h SUPPLIED: Tabs 10, 25 mg NOTES: May produce profound orthostatic hypotension, especially with diuretic use; may potenti- ate the effects of vasopressor agents; increased bowel movements and explosive diarrhea possible; interaction with tricyclic antidepressants reduces effectiveness Guanfacine (Tenex) COMMON USES: HTN ACTIONS: Centrally acting α-adrenergic agonist DOSAGE: Initially, 1 mg hs; ↑ by 1 mg/24h increments to a max of 3 mg/24h; split the dose bid if BP increases at the end of the dosing interval SUPPLIED: Tabs 1, 2 mg NOTES: Use with a thiazide diuretic recommended; sedation and drowsiness common; rebound HTN possible with abrupt cessation of therapy Haemophilus B Conjugate Vaccine (Prohibit, Comvax, others) COMMON USES: Routine immunization of children against diseases caused by H. influenzae type B ACTIONS: Active immunization against Haemophilus B DOSAGE: Peds. 0.5 mL (25 mg) IM in deltoid or vastus lateralis SUPPLIED: Inj 7.5, 10, 15, 25 µg/0.5 mL NOTES: Booster NOT required; observe for anaphylaxis. (See Table 22–9, page 636.) Haloperidol (Haldol) COMMON USES: Psychotic disorders, agitation, Tourette’s disorders, and hyperactivity in children ACTIONS: Antipsychotic, neuroleptic DOSAGE: Adults. Moderate symptoms: 0.5–2.0 mg PO bid–tid. Severe symptoms or agitation: 3–5 mg PO bid–tid or 1–5 mg IM q4h PRN (max 100 mg/d). Peds. 3–6 y: 0.01–0.03 mg/kg/24h PO qd. 6–12 y: Initially, 0.5–1.5 mg/24h PO; ↑ by increments of 0.5 mg/24h to maintenance of 2–4 mg/24h (0.05–0.1 mg/kg/24h) or 1–3 mg/dose IM q4–8h to a max of 0.1 mg/kg/24h; Tourette’s syndrome may require up to 15 mg/24h PO SUPPLIED: Tabs 0.5, 1, 2, 5, 10, 20 mg; conc liq 2 mg/mL; inj 5 mg/mL; decanoate inj 50, 100 mg/mL NOTES: Can cause extrapyramidal symptoms and hypotension; ↓ dose in elderly Haloprogin (Halotex) COMMON USES: Topical treatment of tinea pedis, tinea cruris, tinea corporis, tinea manus ACTIONS: Topical antifungal DOSAGE: Adults. Apply bid for up to 2 wk; intertriginous may require up to 4 wk SUPPLIED: 1% Cream; soln 22 548 Clinician’s Pocket Reference, 9th Edition Heparin Used for emergency cardiac care (see Chapter 21) COMMON USES: Rx and prevention of DVT and PE, AF with emboli formation, and acute arterial occlusion ACTIONS: Acts with antithrombin III to inactivate thrombin and inhibit thromboplastin formation DOSAGE: Adults. Prophylaxis: 3000–5000 U SC q8–12h. Thrombosis Rx: Loading dose of 50–75 U/kg IV, then 10–20 U/kg IV qh (adjust based on PTT). Peds. Infants: Loading dose 50 U/kg IV bolus, then 20 U/kg/h IV by cont inf. Children: Loading dose 50 U/kg IV, then 15–25 U/kg cont inf or 100 U/kg/dose q4h IV intermittent bolus SUPPLIED: Inj 10, 100, 1000, 2000, 2500, 5000, 7500, 10,000, 20,000, 40,000 U/mL NOTES: Follow PTT, thrombin time, or activated clotting time to assess effectiveness; heparin has little effect on the prothrombin time; with proper dose, PTT is about 1.5–2 × the control; can cause thrombocytopenia; follow platelet counts Hepatitis A Vaccine (Havrix, Vaqta) COMMON USES: Prevention of hepatitis A in individuals at high risk, eg, travelers, those in certain professions, or those practicing high-risk behavior ACTIONS: Provides active immunity DOSAGE: (Expressed as ELISA units [EL.U]) Havrix: Adults. 1440 EL.U. as a single IM dose. Peds >2 y. 720 EL.U. as a single IM dose. Vaqta: Adults. 50 U as a single IM dose. Peds. 25 U as a single IM dose SUPPLIED: Inj 720 EL.U./0.5 mL, 1440 EL.U./1 mL.; 50 U/mL NOTES: Booster is recommended 6–12 mo after primary vaccination Hepatitis B Immune Globulin [HBIG] (BayhepB, NAbi-HB) COMMON USES: Exposure to HBsAg-positive materials, eg, blood, plasma, or serum (accidental needle-stick, mucous membrane contact, or oral ingestion) ACTIONS: Passive immunization DOSAGE: Adults & Peds. 0.06 mL/kg IM to a max of 5 mL; within 24 h of needle-stick or percuta- neous exposure; within 14 d of sexual contact; repeat 1 and 6 mo after exposure SUPPLIED: Inj NOTES: Administered in gluteal or deltoid muscle; if exposure continues, the patient should also re- ceive the hepatitis B vaccine Hepatitis B Vaccine (Engerix-B, Recombivax HB) COMMON USES: Prevention of hepatitis B ACTIONS: Active immunization DOSAGE: Adults. 3 IM doses of 1 mL each, the first 2 doses given 1 mo apart, the 3rd 6 mo after the first. Peds. 0.5 mL IM given on the same schedule as for adults (see Table 22–9, page 636) SUPPLIED: Engerix-B: Inj 20 µg/mL; Ped inj 10 µg/0.5 mL. Recombivax HB: Inj 10 and 40 µg/mL; Ped inj 5 µg/0.5 mL NOTES: Administer IM injections for adults and older Peds in the deltoid; in other Peds, administer in the anterolateral thigh; may cause fever, inj site soreness; derived from recombinant DNA tech- nology Hetastarch (Hespan) COMMON USES: Plasma volume expansion as an adjunct in the treatment of shock and leukaphere- sis ACTIONS: Synthetic colloid with actions similar to those of albumin DOSAGE: 500–1000 mL (do not exceed 1500 mL/d) IV at a rate not to exceed 20 mL/kg/h. Leuka- pheresis: 250–700 mL SUPPLIED: Inj 6 g/100 mL NOTES: NOT a substitute for blood or plasma; contra in patients with severe bleeding disorders, se- 22 vere CHF, or renal failure with oliguria or anuria 22 Commonly Used Medications 549 Hydralazine (Apresoline, others) COMMON USES: Moderate to severe HTN ACTIONS: Peripheral vasodilator DOSAGE: Adults. Begin at 10 mg PO qid, then ↑ to 25 mg qid to max of 300 mg/d. Peds. 0.75–3 mg/kg/24h PO ÷ q12–6h SUPPLIED: Tabs 10, 25, 50, 100 mg; inj 20 mg/mL NOTES: Use caution with impaired hepatic function and CAD; compensatory sinus tachycardia can be eliminated with the addition of propranolol; chronically high doses can cause SLE-like syn- drome and Vitamin B6 deficiency; SVT can occur following IM administration; dosage adjustment in renal impairment Hydrochlorothiazide (Hydrodiuril, Esidrix, others) COMMON USES: Edema, HTN, and CHF ACTIONS: Thiazide diuretic; inhibits Na reabsorption in the distal tubule DOSAGE: Adults. 25–100 mg/d PO in single or ÷ doses. Peds. <6 mo: 2–3 mg/kg/d in 2 ÷ doses. >6 mo: 2 mg/kg/d in 2 ÷ doses SUPPLIED: Tabs 25, 50, 100 mg; caps 12.5 mg; oral soln 50 mg/5 mL NOTES: Hypokalemia frequent; hyperglycemia, hyperuricemia, hyperlipidemia, and hyponatremia common Hydrochlorothiazide and Amiloride (Moduretic) COMMON USES: HTN; adjunctive therapy for CHF ACTIONS: Combined effects of a thiazide diuretic and a potassium-sparing diuretic DOSAGE: 1–2 tabs/d PO SUPPLIED: Tabs (amiloride/hydrochlorothiazide) 5 mg/50 mg NOTES: Do NOT give to diabetics or patients with renal failure Hydrochlorothiazide and Spironolactone (Aldactazide) COMMON USES: Edema (CHF, cirrhosis) and HTN ACTIONS: Combined effects of a thiazide diuretic and a K-sparing diuretic DOSAGE: 25–200 mg each component/d in ÷ doses SUPPLIED: Tabs (hydrochlorothiazide/spironolactone) 25 mg/25 mg, 50 mg/50 mg Hydrochlorothiazide and Triamterene (Dyazide, Maxzide) COMMON USES: Edema and HTN ACTIONS: Combined effects of a thiazide diuretic and a K-sparing diuretic DOSAGE: Dyazide: 1–2 caps PO qd–bid. Maxzide: 1 tab/d PO SUPPLIED: (triamterene/HCTZ) 37.5 mg/25 mg, 50 mg/25 mg, 75 mg/50 mg NOTES: HCTZ component in Maxzide more bioavailable than Dyazide; can cause hyperkalemia as well as hypokalemia; follow serum K levels Hydrocodone and Acetaminophen (Lorcet, Vicodin, others) [C-III] COMMON USES: Moderate to severe pain; hydrocodone has antitussive properties ACTIONS: Narcotic analgesic with nonnarcotic analgesic DOSAGE: 1–2 caps or tabs PO q4–6h PRN SUPPLIED: Many different combinations; specify hydrocodone/acetaminophen dose. Caps 5/500; tabs 2.5/500, 5/400, 5/500, 7.5/400, 10/400, 7.5/500, 7.5/650, 7.5/750, 10/325, 10/400, 10/500, 10/650; elixir and soln (fruit punch flavor) 2.5 mg hydrocodone/167 mg acetaminophen/5 mL Hydrocodone and Aspirin (Lortab ASA, others) [C-III] COMMON USES: Moderate-to-severe pain ACTIONS: Narcotic analgesic with NSAID DOSAGE: 1–2 PO q4–6h PRN SUPPLIED: 5 mg hydrocodone/500 mg aspirin/tab 22 550 Clinician’s Pocket Reference, 9th Edition Hydrocodone and Guaifenesin (Hycotuss Expectorant, others) [C-III] COMMON USES: Nonproductive cough associated with respiratory infection ACTIONS: Expectorant plus cough suppressant DOSAGE: Adults & Peds. >12 y: 5 mL q4h, pc and hs. Peds. <2 y: 0.3 mg/kg/d ÷ qid; 2–12 y: 2.5 mL q4h pc and hs SUPPLIED: Hydrocodone 5 mg/guaifenesin 100 mg/5 mL Hydrocodone and Homatropine (Hycodan, others) [C-III] COMMON USES: Relief of cough ACTIONS: Combination antitussive DOSAGE: Dose based on hydrocodone. Adults. 5–10 mg q4–6h. Peds. 0.6 mg/kg/d ÷ tid–qid SUPPLIED: Syrup 5-mg hydrocodone/5 mL; tabs 5-mg hydrocodone Hydrocodone and Ibuprofen (Vicoprofen) [C-III] COMMON USES: Moderate to severe pain (<10 d) ACTIONS: Narcotic with NSAID DOSAGE: 1–2 tabs q4–6h PRN SUPPLIED Tabs 7.5 mg hydrocodone/200 mg ibuprofen Hydrocodone and Pseudoephedrine (Entuss-D, Histussin-D, others) [C-III] COMMON USES: Cough and nasal congestion ACTIONS: Narcotic cough suppressant with decongestant DOSAGE: 5 mL qid, PRN SUPPLIED: Entuss-D 5-mg hydrocodone/30 mg pseudoephedrine/5 mL; Histussin-D 5-mg hy- drocodone/60 mg pseudoephedrine/5 mL Hydrocodone, Chlorpheniramine, Phenylephrine, Acetaminophen, and Caffeine (Hycomine Compound) [C-III] COMMON USES: Cough and symptoms of upper respiratory infections ACTIONS: Narcotic cough suppressant with decongestants and analgesic DOSAGE: 1 PO, q4h, PRN SUPPLIED: Hydrocodone 5 mg/chlorpheniramine/2 mg/phenylephrine/10 mg/acetaminophen 250 mg/caffeine 30 mg/tab Hydrocortisone See Steroids (topical Table 22–6, pages 628–630, systemic, Table 22–5, page 627) Hydrocortisone, Rectal (Anusol-HC Suppository, C Ortifoam Rectal, Proctocort others) COMMON USES: Adjunct to painful anorectal conditions; radiation proctitis, management of ulcer- ative colitis ACTIONS: Antiinflammatory steroid DOSAGE: Adults. Ulcerative colitis 10–100 mg rectally qd–bid 2–3 wk 1–2×/d for 2–3 wk SUPPLIED: Hydrocortisone acetate: Rectal aerosol 90 mg/applicator; supp 25 mg; Hydrocortisone base: Rectal 1%; rectal susp: 100 mg/60 mL Hydrocortisone, Topical (see also Table 22–6, pages 628–630) Hydromorphone (Dilaudid) [C-II] COMMON USES: Moderate to severe pain ACTIONS: Narcotic analgesic DOSAGE: 1–4 mg PO, IM, IV, or PR q4–6h PRN; 3 mg PR q6–8h PRN SUPPLIED: Tabs 1, 2, 3, 4, 8 mg; liq 5 mg/mL; inj 1, 2, 4, 10 mg/mL; supp 3 mg 22 NOTES: 1.5 mg IM = 10 mg of morphine IM 22 Commonly Used Medications 551 Hydroxyurea (Hydrea, Droxia) COMMON USES: CML, head and neck cancer, ovarian cancer, melanoma, colon cancer, acute leukemia, and sickle cell anemia, HIV ACTIONS: Probable inhibitor of the ribonucleotide reductase system DOSAGE: 50–75 mg/kg for WBC counts of >100,000 cells/mL; 20–30 mg/kg in refractory CML. HIV: 1000–1500 mg/d in single or ÷ doses SUPPLIED: Caps 200, 300, 400, 500 mg NOTES: Toxicity symptoms: Myelosuppression (primarily leukopenia), nausea and vomiting, rashes, facial erythema, radiation recall reactions, and renal dysfunction; dosage adjustment in renal dys- function Hydroxyzine (Atarax, Vistaril) COMMON USES: Anxiety, tension, sedation, itching ACTIONS: Antihistamine, anxiety DOSAGE: Adults. Anxiety or sedation: 50–100 mg PO or IM qid or PRN (max 600 mg/d). Itching: 25–50 mg PO or IM tid–qid. Peds. 0.5–1.0 mg/kg/24h PO or IM q6h SUPPLIED: Tabs 10, 25, 50, 100 mg; caps 25, 50, 100 mg; syrup 10 mg/5 mL; susp 25 mg/5 mL; inj 25, 50 mg/mL NOTES: Useful in potentiating effects of narcotics; NOT for IV use; drowsiness and anticholinergic effects common Hyoscyamine (Anaspaz, Cystospaz, Levsin, others) COMMON USES: Spasm associated with GI and bladder disorders DOSAGE: Adults. 0.125–0.25 mg (1–2 tabs) SL 3–4/×/d, pc and hs; 1 SR caps q12h SUPPLIED: Caps SR [Cystospaz-M, Levsinex]) Hyoscyamine, Atropine, Scopolamine, and Phenobarbital (Donnatal, others) COMMON USES: Irritable bowel, spastic colitis, peptic ulcer, spastic bladder DOSAGE: 0.125–0.25 mg (1–2 tabs) 3–4×/d, 1 cap q12h (SR), 5–10 mL elixir 3–4×/d or q8h Ibuprofen (Motrin, Rufen, Advil, others) COMMON USES: Arthritis and pain ACTIONS: NSAID DOSAGE: Adults. 200–800 mg PO bid–qid. Peds. 30–40 mg/kg/d in 3–4 ÷ doses SUPPLIED: Tabs 100, 200, 400, 600, 800 mg; chewable tabs 50, 100 mg; caps 200 mg; susp 100 mg/2.5 mL, 100 mg/5 mL, 40 mg/mL Ibutilide (Corvert) COMMON USES: Rapid conversion of Afib or flutter ACTIONS: Class III antiarrhythmic agent DOSAGE: 0.01 mg/kg (max 1 mg) IV inf over 10 min. May be repeated once SUPPLIED: Inj 0.1 mg/mL NOTES: Do NOT administer Class I or III antiarrhythmics concurrently or within 4 h of ibutilide inf Idarubicin (Idamycin) COMMON USES: AML (in combination with cytarabine), CML in blast crisis, and ALL ACTIONS: DNA intercalating agent; inhibits of DNA topoisomerases I and II DOSAGE: 10–12 mg/m2/d for 3–4 d SUPPLIED: Inj 1 mg/mL (5-, 10-, 20-mg vials NOTES: Toxicity symptoms: Myelosuppression, cardiotoxicity, nausea and vomiting, mucositis, alopecia, and irritation at sites of IV administration; rare changes in renal and hepatic function; dosage adjustment in renal or hepatic dysfunction 22 552 Clinician’s

Pocket Reference, 9th Edition Ifosfamide (Ifex, Holoxan) COMMON USES: Lung cancer (small-cell and non-small-cell), soft tissue sarcoma, testicular cancer, and non-Hodgkin’s lymphoma ACTIONS: Alkylating agent DOSAGE: 1.2 g/m2/d for 5 d by bolus or cont inf; 2.4 g/m2/d for 3 d; with MESNA uroprotection (see MESNA) SUPPLIED: Inj 1, 3 g NOTES: Toxicity symptoms: Hemorrhagic cystitis, nephrotoxicity, nausea and vomiting, mild to moderate leukopenia, lethargy and confusion, alopecia, and hepatic enzyme elevations; dosage ad- justment in renal impairment Imipenem-Cilastatin (Primaxin) COMMON USES: Serious infections caused by a wide variety of susceptible bacteria; inactive against S. aureus, group A and B streptococci, etc ACTIONS: Bactericidal; interferes with cell wall synthesis DOSAGE: Adults. 250–500 mg (imipenem) IV q6h. Peds. 60–100 mg/kg/24h IV ÷ q6h SUPPLIED: Inj (imipenem/cilastatin) 250 mg/250 mg, 500 mg/500 mg NOTES: Seizures may occur if drug accumulates; ↓ dosage for renal insufficiency to avoid drug ac- cumulation if calculated CrCl is <70 mL/min Imipramine (Tofranil) COMMON USES: Depression, enuresis, and chronic pain ACTIONS: Tricyclic antidepressant; ↑ synaptic conc of serotonin or norepinephrine in the CNS DOSAGE: Adults. Hospitalized: Start at 100 mg/24h PO in ÷ doses; can ↑ over several weeks to 250–300 mg/24h. Outpatient: Maintenance of 50–150 mg PO hs, not to exceed 200 mg/24h. Peds. Antidepressant: 1.5–5.0 mg/kg/24h ÷ 1–4×/d. Enuresis: >6 y: 10–25 mg PO hs; ↑ by 10–25 mg at 1–2-wk intervals; treat for 2–3 mo, then taper SUPPLIED: Tabs 10, 25, 50 mg; caps 75, 100, 125, 150 mg NOTES: Do NOT use with MAO inhibitors; less sedation than with amitriptyline Imiquimod Cream, 5% (Aldara) COMMON USES: External genital warts ACTIONS: Exact mechanism unknown; may induce cytokines DOSAGE: Applied 3×/wk; leave on skin for 6–10 h, continue therapy for a max of 16 wk SUPPLIED: Single-dose packets (250 mg of the cream) NOTES: Local skin reactions common Immune Globulin, Intravenous (Gamimmune N, Sandoglobulin, Gammar IV) COMMON USES: IgG antibody deficiency disease states (eg, congenital agammaglobulinemia), CVH, and BMT; and ITP ACTIONS: IgG supplementation DOSAGE: Adults & Peds. Immunodeficiency: 100–200 mg/kg/mo IV at a rate of 0.01–0.04 mL/kg/min to a max of 400 mg/kg/dose. ITP: 400 mg/kg/dose IV qd for 5 d. BMT: 500 mg/kg/wk SUPPLIED: Inj NOTES: Adverse effects associated mostly with rate of infusion Indapamide (Lozol) COMMON USES: HTN and CHF ACTIONS: Thiazide diuretic; enhances Na, Cl, and water excretion in the proximal segment of the distal tubule DOSAGE: 1.25–5.0 mg/d PO SUPPLIED: Tabs 1.25, 2.5 mg 22 NOTES: Doses >5 mg do NOT have additional effects on lowering BP 22 Commonly Used Medications 553 Indinavir (Crixivan) COMMON USES: HIV infection when antiretroviral therapy is indicated ACTIONS: Protease inhibitor; inhibits maturation of immature noninfectious virions to mature in- fectious virus DOSAGE: 800 mg PO q8h SUPPLIED: Caps 200, 400 mg NOTES: Use in combination with other antiretroviral agents; take on an empty stomach; may cause nephrolithiasis; drink six 8-oz glasses of water/d; numerous drug interactions; dosage adjustment in hepatic impairment Indomethacin (Indocin) COMMON USES: Arthritis and closure of the ductus arteriosus; tocolytic ACTIONS: Inhibits prostaglandin synthesis DOSAGE: Adults. 25–50 mg PO bid–tid, to a max of 200 mg/d. SR dosed 1–2 × day Tocolysis: 50–100 10 PR, then 25 mg PO/PR q4–6h/× 48h. Infants: 0.2–0.25 mg/kg/dose IV; may be repeated in 12–24 h for up to 3 doses SUPPLIED: Inj 1 mg/vial; caps 25, 50 mg; SR caps 75 mg; supp 50 mg; susp 25 mg/5 mL NOTES: Monitor renal function carefully Infliximab (Remicade) COMMON USES: Moderate to severe Crohn’s disease; RA (in combination with methotrexate) ACTIONS: IgG1κ neutralizes biologic activity of TNFα DOSAGE: Crohn’s disease: 5 mg/kg IV inf, may follow with subsequent doses given at 2 and 6 wk after initial inf. RA: 3 mg/kg IV inf at 0, 2, 6 wk, followed by q 8 wk SUPPLIED: Inj NOTES: May cause hypersensitivity reaction, made up of human constant and murine variable re- gions; patients are predisposed to infection Influenza Vaccine (Fluzone, Fluogen, Flushield, Flu-immune) COMMON USES: Prevention of influenza in high-risk populations (chronic medical conditions, eg, heart disease, lung disease, or diabetes; children with asthma; residents of chronic care facilities; and any person >50 y). Health care workers or members of households who may come into contact with these patients also encouraged to be immunized ACTIONS: Active immunization to inactivated virus grown in eggs DOSAGE: 0.5 mL/dose IM in adults. Optimal time for vaccination in the U.S. is October–November because protection begins 1–2 wk after vaccination and lasts up to 6 mo SUPPLIED: Each year, specific vaccines manufactured based on predictions of the strains likely to be active in the influenza season. The flu season generally December–Spring in the U.S. (Flu- immune = surface antigen, Fluogen = split virus, Flurone = whole virus) NOTES: Soreness at the inj site and fever or malaise common after inj; severe reactions rare. Whole or split virus usually given to adults; give children <13 y split virus or purified surface antigen form to decrease febrile reactions Insulin COMMON USES: DM refractory to diet change or oral hypoglycemic agents; adjunct to the manage- ment of acute life-threatening hyperkalemia ACTIONS: Insulin supplementation DOSAGE: Based on serum glucose levels; usually given SC but can also be given IV or IM (only regular insulin can be given IV) SUPPLIED: See Table 22–2 (page 622) NOTES: Highly purified insulins ↑ free insulin; monitor patients closely for several weeks when changing doses 22 554 Clinician’s Pocket Reference, 9th Edition Interferon Alfa (Roferon-A, Intron A) COMMON USES: HCL, Kaposi’s sarcoma, multiple myeloma, CML, renal cell carcinoma, bladder cancer, melanoma, and chronic hepatitis C ACTIONS: Direct antiproliferative action against tumor cells; modulation of the host immune re- sponse DOSAGE: Dictated by treatment protocol. Alfa-2a (Roferon): 3 million IU/d for 16–24 wk SC or IM. Alfa-2b (Intron A): 2 million IU/m2 IM or SC 3×/wk for 2–6 mo; intravesical 50–100 million IU in 50 mL/wk NS × 6 SUPPLIED: Injectable forms NOTES: May cause flu-like symptoms; fatigue common; anorexia occurs in 20–30% of patients; neurotoxicity may occur at high doses; neutralizing antibodies can occur in up to 40% of patients receiving prolonged therapy Interferon Alfa-2B and Ribavirin Combination (Rebetron) COMMON USES: Chronic hepatitis C in patients with compensated liver disease who have relapsed following α-interferon therapy ACTIONS: Combination antiviral agents DOSAGE: 3 million U Intron A SC 3×/wk with 1000–1200 mg of Rebtrol PO ÷ bid dose for 24 wk; Patients <75 kg: 1000 mg of Rebetrol/d SUPPLIED: Patients <75 kg: Combination pack; 6 vials Intron A (3 million U/0.5 mL ) with 6 sy- ringes and alcohol swabs; 70 Rebtrol caps. One 18-million-U multidose vial of Intron A inj (22.8 million U/3.8 mL; 3 million U/0.5 mL) and 6 syringes and alcohol swabs; 70 Rebetrol caps. One 18 million IU Intron A inj multidose pen (22.5 million IU/1.5 mL; 3 million IU/0.2 mL) and 6 dis- posable needles and alcohol swabs 70 Rebetrol caps. Patients >75 kg: Identical except for 84 Rebe- trol caps/pack NOTES: Instruct patients in self-administration of SC Intron A Interferon Alfacon-1 (Infergen) COMMON USES: Management of chronic hepatitis C ACTIONS: Biologic response modifier DOSAGE: 9 µg SC 3×/wk SUPPLIED: Inj 9, 15 µg NOTES: At least 48 h between inj Interferon β-1B (Betaseron) COMMON USES: Management of MS ACTIONS: Biologic response modifier DOSAGE: 0.25 mg SC qod SUPPLIED: Powder for inj 0.3 mg NOTES: May cause flu-like syndrome Interferon Gamma-1B (Actimmune) COMMON USES: Chronic granulomatous disease ACTIONS: Biologic response modifier DOSAGE: 50 mg/m2 SC 3×/wk SUPPLIED: Inj 100 mg NOTES: 100 mg = 3 million U; may cause flu-like syndrome Ipecac Syrup See also Chapter 21 COMMON USES: Drug overdose and certain cases of poisoning ACTIONS: Irritation of the GI mucosa; stimulation of the chemoreceptor trigger zone DOSAGE: Adults. 15–30 mL PO, followed by 200–300 mL of water; if no emesis occurs in 20 min, 22 may repeat once. Peds. Children 6–12 mo: 5–10 mL PO, followed by 10–20 mL/kg of water; if no 22 Commonly Used Medications 555 emesis occurs in 20 min, may repeat once. Children 1–12 y: 15 mL PO followed by 10–20 mL/kg of water; if no emesis occurs in 20 min, may repeat once SUPPLIED: Syrup 15, 30 mL NOTES: Do NOT use for ingestion of petroleum distillates or strong acid, base, or other corrosive or caustic agents; NOT for use in comatose or unconscious patients; caution in CNS depressant over- dose Ipratropium (Atrovent) COMMON USES: Bronchospasm associated with COPD, bronchitis, and emphysema; rhinorrhea ACTIONS: Synthetic anticholinergic agent similar to atropine DOSAGE: Adults & Peds >12 y. 2–4 puffs qid. Nasal: 2 sprays/nostril bid–tid SUPPLIED: Met-dose inhaler 18 µg/dose; soln for inhal 0.02%; nasal spray 0.03%, 0.06% NOTES: Not for initial treatment of acute episodes of bronchospasm Irbesartan (Avapro) COMMON USES: HTN ACTIONS: Angiotensin II receptor antagonists DOSAGE: 150 mg/d PO, may be ↑ to 300 mg/d SUPPLIED: Tabs 75, 150, 300 mg Irinotecan (Camptosar) COMMON USES: Advanced colorectal cancer; lung cancer ACTIONS: Topoisomerase I inhibitor; interferes with DNA synthesis Dose: 125–250 mg/m2 weekly to every other week SUPPLIED: Inj 20 mg/mL NOTES: Toxicity symptoms: Myelosuppression, diarrhea (acute or subacute), nausea and vomiting, abdominal cramping, and alopecia. Diarrhea dose-limiting in many studies; acute diarrhea associ- ated with crampy abdominal pain successfully treated with atropine; subacute diarrhea treated with Imodium or loperamide. Diarrhea correlated to levels of metabolite SN-38 Iron Dextran (Dexferrum, InFeD) COMMON USES: Iron deficiency when oral supplementation not possible ACTIONS: Parenteral iron supplementation DOSAGE: Based on estimate of iron deficiency, given IM/IV. A 0.5-mL test dose (0.25 mL in in- fants) prior to starting iron dextran. Total replacement dose (mL) = 0.0476 × weight (kg) × [desired hemoglobin (g/dL) – measured hemoglobin (g/dL)] + 1 mL/5 kg weight (max 14 mL). Max daily dose: Adults >50 kg. 100 mg Fe. Peds <5 kg. 25 mg Fe, 5–10 kg: 50 mg Fe, 0–50 kg: 100 mg Fe SUPPLIED: Inj 50 mg (Fe)/mL NOTES: Use test dose because anaphylaxis common; may be given deep IM using the “Z-track” technique, although IV route preferred Isoetharine (Bronkosol, Bronkometer) COMMON USES: Bronchial asthma and reversible bronchospasm ACTIONS: Sympathomimetic bronchodilator DOSAGE: Adults. 0.25–1.0 mL diluted 1:3 with saline q4–6h. Peds. 0.01 mL/kg; min dose 0.1 mL; max dose 0.5 mL; dilute with saline q4–6h SUPPLIED: Soln for inhal; aerosol Isoniazid (INH) COMMON USES: Treatment and prophylaxis of Mycobacterium spp infections ACTIONS: Bactericidal; interferes with mycolic acid synthesis, thus disrupting the bacterial cell wall 22 556 Clinician’s Pocket Reference, 9th Edition DOSAGE: Adults. Active TB: 5 mg/kg/24h PO or IM (usually 300 mg/d). Prophylaxis: 300 mg/d PO for 6–12 mo. Peds. Active TB: 10–20 mg/kg/24h PO or IM to a max of 300 mg/d. Prophylaxis: 10 mg/kg/24h PO SUPPLIED: Tabs 50, 100, 300 mg; syrup 50 mg/5 mL; inj 100 mg/mL NOTES: Can cause severe hepatitis; given with other antituberculous drugs for active TB; consult MMWR for the latest recommendations on the treatment and prophylaxis of TB; IM route rarely used; to prevent peripheral neuropathy, give pyridoxine 50–100 mg/d; dosage adjustment in hepatic impairment Isoproterenol (Isuprel, Medihaler-Iso) Used for emergency cardiac care (see Chapter 21) COMMON USES: Shock, cardiac arrest, and AV nodal block; antiasthmatic ACTIONS: β1- and β2-receptor stimulant DOSAGE: Adults. For emergency cardiac care, also see Chapter 21. Shock: 1–4 mg/min IV inf; titrate to effect. AV nodal block: 20–60 mg IV push; may repeat q 3–5 min; maintenance 1–5 mg/min IV inf. Inhalation: 1–2 inhal 4–6×/d. Peds. For emergency cardiac care, also see Chapter 21. Inhal: 1–2 inhal 4–6×/d SUPPLIED: Metered inhaler; soln for neb 0.5%, 1%; inj 0.02 mg/mL, 0.2 mg/mL NOTES: Contra in tachycardia; pulse >130 may induce ventricular arrhythmias. (See Table 20–10, page 637.) Isosorbide Dinitrate (Isordil, Sorbitrate) COMMON USES: Rx and prevention of angina pectoris ACTIONS: Relaxation of vascular smooth muscle DOSAGE: Acute angina: 5–10 mg PO (chewable tabs) q2–3h or 2.5–10 mg SL PRN q 5–10 min; >3 doses should not be given in a 15–30-min period. Angina prophylaxis: 5–60 mg PO tid SUPPLIED: Tabs 5, 10, 20, 30, 40 mg; SR tabs 40 mg; SL tabs 2.5, 5, 10 mg; chewable tabs 5, 10 mg; SR caps 40 mg NOTES: Do NOT give nitrates on a chronic q6h or qid basis because of development of tolerance; can cause headaches; higher oral dose usually needed to achieve same results as SL forms Isosorbide Mononitrate (Ismo, Imdur) COMMON USES:

Prevention of angina pectoris ACTIONS: Causes relaxation of the vascular smooth muscle DOSAGE: 20 mg PO bid, with the 2 doses given 7 h apart or ER (Imdur) 30–120 mg/d PO SUPPLIED: Tabs 10, 20 mg; ER 30, 60, 120 mg Isotretinoin [13-cis Retinoic Acid] (Accutane) COMMON USES: Refractory severe acne ACTIONS: Retinoic acid derivative DOSAGE: 0.5–2 mg/kg/d PO ÷ bid SUPPLIED: Caps 10, 20, 40 mg NOTES: Contra in PRG and lactation; isolated reports of depression, psychosis, suicidal thoughts; dosage adjustment in hepatic impairment Isradipine (Dyna-Circ) COMMON USES: HTN and CHF ACTIONS: Ca channel-blocker DOSAGE: 2.5–10 mg PO bid SUPPLIED: Caps 2.5, 5.0 mg; tabs CR 5, 10 mg Itraconazole (Sporanox) COMMON USES: Systemic fungal infections caused by Aspergillus, Blastomycosis, and Histoplasma 22 ACTIONS: Inhibits synthesis of ergosterol 22 Commonly Used Medications 557 DOSAGE: 200 mg PO or IV qd–bid SUPPLIED: Caps 100 mg; soln 10 mg/mL; inj 10 mg/mL NOTES: Administer with meals or cola; do NOT use concurrently with H2-antagonist, omeprazole, antacids, terfenadine, astemizole, or cisapride; numerous other interactions Kaolin-Pectin (Kaodene, Kao-Spen, Kapectolin) COMMON USES: Diarrhea ACTIONS: Adsorbent demulcent DOSAGE: Adults. 60–120 mL PO after each loose stool or q3–4h PRN. Peds. 3–6 y: 15–30 mL/dose PO PRN. 6–12 y: 30–60 mL/dose PO PRN SUPPLIED: Multiple OTC forms NOTES: Also available with opium (Parepectolin [C-V]) Ketoconazole (Nizoral) COMMON USES: Systemic fungal infections (candidiasis, chronic mucocutaneous candidiasis, blas- tomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis); topical cream for localized fungal infections due to dermatophytes and yeast; short-term treatment of prostate cancer when rapid reduction of testosterone needed (ie, spinal cord compression) ACTIONS: Inhibits fungal cell wall synthesis DOSAGE: Adults. Oral: 200 mg PO qd; ↑ to 400 mg PO qd for serious infections; prostate cancer 400 mg PO tid (short term). Topical: Apply to the affected area qd (cream or shampoo). Peds >2 y. 5–10 mg/kg/24h PO ÷ q12–24h SUPPLIED: Tabs 200 mg; topical cream 2%; shampoo 2% NOTES: Systemic use associated with hepatotoxicity; monitor LFT; drug interaction with any agent ↑ gastric pH prevents absorption of ketoconazole; avoid concurrent use with cisapride; may en- hance oral anticoagulants; may react with alcohol to produce a disulfiram-like reaction; numerous other drug interactions Ketoprofen (Orudis, Oruvail) COMMON USES: Arthritis and pain ACTIONS: NSAID; inhibits prostaglandin synthesis DOSAGE: 25–75 mg PO tid–qid, to a max of 300 mg/d SUPPLIED: Tabs 12.5 mg; caps 50, 75 mg; caps, SR 100, 150, 200 mg Ketorolac (Toradol) COMMON USES: Arthritis and pain ACTIONS: NSAID; inhibits prostaglandin synthesis DOSAGE: 15–30 mg IV/IM q6h or 10 mg PO qid SUPPLIED: Tabs 10 mg; inj 15 mg/mL, 30 mg/mL NOTES: Do NOT use for longer than 5 d; adjust dose for age and renal dysfunction Ketorolac Ophthalmic (Acular) COMMON USES: Relief of ocular itching caused by seasonal allergic conjunctivitis ACTIONS: NSAID DOSAGE: 1 gt qid SUPPLIED: Soln 0.5% Labetalol (Trandate, Normodyne) COMMON USES: HTN and hypertensive emergencies ACTIONS: α- and β-Adrenergic blocking agent DOSAGE: Adults. HTN: Initially, 100 mg PO bid; then 200–400 mg PO bid. Hypertensive emer- gency: 20–80 mg IV bolus, then 2 mg/min IV infusion, titrated to effect. Peds. Oral: 3–20 mg/kg/d in ÷ doses. Hypertensive emergency: 0.4–3 mg/kg/h IV cont inf SUPPLIED: Tabs 100, 200, 300 mg; inj 5 mg/mL. (See Table 22–10, page 637.) 22 558 Clinician’s Pocket Reference, 9th Edition Lactic Acid and Ammonium Hydroxide [Ammonium Lactate] (Lac-Hydrin) COMMON USES: Severe xerosis and ichthyosis ACTIONS: Emollient moisturizer DOSAGE: Apply bid SUPPLIED: Lactic acid 12% with ammonium hydroxide Lactobacillus (Lactinex Granules) COMMON USES: Control of diarrhea, especially after antibiotic therapy ACTIONS: Replaces normal intestinal flora DOSAGE: Adult and Peds >3 y. 1 packet, 2 caps, or 4 tabs with meals or liqs tid–qid SUPPLIED: Tabs; caps; EC caps; powder in packets Lactulose (Chronulac, Cephulac) COMMON USES: Hepatic encephalopathy; laxative ACTIONS: Acidifies the colon, allowing ammonia to diffuse into the colon DOSAGE: Adults. Acute hepatic encephalopathy: 30–45 mL PO q1h until soft stools are observed, then tid–qid. Chronic laxative therapy: 30–45 mL PO tid–qid; adjust the dosage q 1–2 d to produce 2–3 soft stools/d. Rectally: 200 g diluted with 700 mL of water instilled PR. Peds. Infants: 2.5–10 mL/24h ÷ tid–qid. Children: 40–90 mL/24h ÷ tid–qid SUPPLIED: Syrup 10 g/15 mL NOTES: Can cause severe diarrhea Lamivudine (Epivir, Epivir-HBV) COMMON USES: HIV infection when therapy warranted based on clinical or immunologic evidence of disease progression, and chronic hepatitis B ACTIONS: Inhibits HIV reverse transcriptase, resulting in viral DNA chain termination DOSAGE: HIV: Adults & Peds >12 y. 150 mg PO bid. Peds <12 y. 4 mg/kg bid. HBV: 100 mg/d SUPPLIED: Tabs 100, 150 mg; soln 5 mg/mL, 10 mg/mL NOTES: Use in combination with zidovudine; use with caution in pediatric patients because of an increased incidence of pancreatitis; adjust dose for renal dysfunction Lamotrigine (Lamictal) COMMON USES: Partial seizures ACTIONS: Phenyltriazine antiepileptic DOSAGE: Adults. Initial dose 50 mg/d PO, followed by 50 mg PO bid for 2 wk, then maintenance dose of 300–500 mg/d in 2 ÷ doses. Peds. 0.15 mg/kg in 1–2 ÷ doses for weeks 1 and 2, then 0.3 mg/kg for weeks 3 and 4, then maintenance dose of 1 mg/kg/d in 1–2 ÷ doses SUPPLIED: Tabs 25, 100, 150, 200 mg; chewable tabs 5, 25 mg NOTES: May cause rash and photosensitivity; value of therapeutic monitoring not established; in- teracts with other antiepileptics Lansoprazole (Prevacid) COMMON USES: Duodenal ulcers, H. pylori infection, erosive esophagitis, and hypersecretory con- ditions ACTIONS: Proton pump inhibitor DOSAGE: 15–30 mg/d PO SUPPLIED: Caps 15, 30 mg Latanoprost (Xalatan) COMMON USES: Refractory glaucoma ACTIONS: Prostaglandin DOSAGE: 1 gtt SUPPLIED: 0.005% Soln 22 NOTES: May darken light irides 22 Commonly Used Medications 559 Leflunomide (Arava) COMMON USES: Active RA ACTIONS: Inhibits pyrimidine synthesis DOSAGE: Initial 100 mg/d for 3 d, followed by 10–20 mg/d SUPPLIED: Tabs 10, 20, 100 mg NOTES: PRG category X DO NOT USE; monitor serum transaminase levels during initial therapy Lepirudin (Refludan) COMMON USES: Heparin-induced thrombocytopenia ACTIONS: Direct inhibitor of thrombin DOSAGE: Bolus 0.4 mg/kg IV, followed by 0.15 mg/kg cont inf SUPPLIED: Inj 50 mg NOTES: Adjust dose based on aPTT ratio; maintain aPTT ratio of 1.5–2.0 Letrozole (Femara) COMMON USES: Advanced breast cancer ACTIONS: Nonsteroidal inhibitor of the aromatase enzyme system DOSAGE: 2.5 mg/d SUPPLIED: Tabs 2.5 mg NOTES: Requires periodic CBC, thyroid function, electrolyte, LFT, and renal monitoring Leucovorin (Wellcovorin) COMMON USES: Overdose of folic acid antagonist; augmentation of 5-FU ACTIONS: Reduced folate source; circumvents the action of folate reductase inhibitors (ie, methotrexate) DOSAGE: Adults & Peds. MTX rescue: 10 mg/m2/dose IV or PO q6h for 72 h until MTX level <10–8. 5-FU: 200 mg/m2/d IV 1–5 d during daily 5-FU treatment or 500 mg/m2/wk with weekly 5-FU therapy. Adjunct to antimicrobials: 5–15 mg/d PO SUPPLIED: Tabs 5, 15, 25 mg; inj NOTES: Many different dosing schedules for leucovorin rescue following MTX therapy Leuprolide (Lupron, Viadur) COMMON USES: Prostate cancer, endometriosis, and CPP ACTIONS: LHRH agonist; paradoxically inhibits release of gonadotropin, resulting in decreased LH and testosterone levels DOSAGE: Adults. Prostate: 7.5 mg IM q 28 d or 22.5 mg IM q 3 mo of depot. Endometriosis (depot only): 3.75 mg IM as a single monthly dose. Viadur: SQ implant 1 × year Peds. CPP: 50 mg/kg/d as a daily SC inj. ↑ by 10 mg/kg/d until total down-regulation achieved. Depot: <25 kg: 7.5 mg IM q 4 wk. >25–37.5 kg: 11.25 mg IM q 4 wk. >37.5 kg: 15 mg IM q 4 wk SUPPLIED: Inj 5 mg/mL; depot forms 3.75, 7.5, 11.25, 15, 22.5, 30 mg; Viadur 12 mo implant NOTES: Toxicity symptoms: Hot flashes, gynecomastia, nausea and vomiting, constipation, anorexia, dizziness, headache, insomnia, paresthesias, peripheral edema, and bone pain (transient “flare reaction” at 7–14 d after the first dose due to testosterone surge) Levalbuterol (Xopenex) COMMON USES: Rx and prevention of bronchospasm ACTIONS: Sympathomimetic bronchodilator DOSAGE: 0.63 mg neb q6–8h SUPPLIED: Soln for inhal 0.63, 1.25 mg/3mL NOTES: Therapeutically active R-isomer of albuterol 22 560 Clinician’s Pocket Reference, 9th Edition Levamisole (Ergamisol) COMMON USES: Adjuvant therapy of Dukes C colon cancer (in combination with 5-FU) ACTIONS: Multiple poorly understood immunostimulatory effects DOSAGE: 50 mg PO q8h for 3 d q 14 d during 5-FU therapy SUPPLIED: Tabs 50 mg NOTES: Toxicity symptoms: Nausea and vomiting, diarrhea, abdominal pain, taste disturbance, anorexia, hyperbilirubinemia, disulfiram-like reaction on alcohol ingestion, minimal bone marrow depression, fatigue, fever, and conjunctivitis Levetiracetam (Keppra) COMMON USES: Partial onset seizures ACTIONS: Unknown DOSAGE: 500 mg PO bid, may be ↑ to a max of 3000 mg/d SUPPLIED: Tabs 250, 500, 750 mg NOTES: May cause dizziness and somnolence; may impair coordination; adjust dosage in renal im- pairment Levobunolol (Betagan, Liquidfilm Ophthalmic) COMMON USES: Glaucoma ACTIONS: β-Adrenergic blocker DOSAGE: 1–2 gtt/d 0.5% or 1–2 gtt 0.25% bid SUPPLIED: Soln 0.25, 0.5% Levocabastine (Livostin) COMMON USES: Allergic seasonal conjunctivitis ACTIONS: Antihistamine DOSAGE: 1 gtt in eye(s) qid up to 4 wk SUPPLIED: 0.05% soln Levofloxacin (Levaquin) COMMON USES: Lower respiratory tract infections, sinusitis, and UTI ACTIONS: Quinolone antibiotic, inhibits DNA gyrase DOSAGE: 250–500 mg/d PO or IV SUPPLIED: Tabs 250, 500 mg; inj 5, 25 mg/mL NOTES: Reliable activity against S. pneumoniae, drug interactions with cation-containing products; renal dosage adjustment Levonorgestrel Implant (Norplant) COMMON USES: Contraceptive (Progestin) DOSAGE: Implant 6 caps in the midforearm during first 7 days of menses SUPPLIED: Kits containing 6 implantable caps, each containing 36 mg NOTES: Prevents pregnancy for up to 5 y; caps may be removed if pregnancy desired Levorphanol (Levo-Dromoran) [C-II] COMMON USES: Moderate to severe pain ACTIONS: Narcotic analgesic DOSAGE: 2 mg PO or SC PRN q6–8h SUPPLIED: Tabs 2 mg; inj 2 mg/mL Levothyroxine (Synthroid) COMMON USES: Hypothyroidism 22 ACTIONS: Supplementation of L-thyroxine 22 Commonly Used Medications 561 DOSAGE: Adults. Initially, 25–50 µg/d PO or IV; ↑ by 25–50 µg/d every month; usual dose 100–200 µg/d. Peds. 0–1 y: 8–10 µg/kg/24h PO or IV. 1–5 y: 4–6 µg/kg/24h PO or IV. >5 y: 3–4 µg/kg/24h PO or IV SUPPLIED: Tabs 25, 50, 75, 88, 100, 112, 125, 150, 175, 200, 300 µg; inj 200, 500 µg NOTES: Titrate dosage based on clinical response and thyroid function tests; can ↑ dosage more rapidly in young to middle-aged patients Lidocaine (Anestacon Topical, Xylocaine, others) Used for emergency cardiac care (see Chapter 21) COMMON USES: Local anesthetic; treatment of cardiac arrhythmias ACTIONS: Anesthetic; class IB antiarrhythmic DOSAGE: Adults. Antiarrhythmic, endotracheal: 5 mg/kg; follow with 0.5 mg/kg in 10 min if effec- tive. IV Load: 1 mg/kg/dose bolus over 2–3 min; repeat in 5–10 min up to 200–300 mg/h; cont inf of 20–50 µg/kg/min or 1–4 mg/min. Peds. Antiarrhythmic, endotracheal, Loading dose: 1 mg/kg; repeat in 10–15 min max total dose of 5 mg/kg; then IV inf 20–50 µg/kg/min. Topical: Apply max 3 mg/kg/dose. Local inj anesthetic: Max 4.5 mg/kg; See Chapter 17. SUPPLIED: Inj (Local) 0.5, 1, 1.5, 2, 4, 10, 20%; (Inj IV) 1% (10 mg/mL, 2% 20 mg/mL); admixture 4, 10, 20%; (IV inf) 0.2%, 0.4%; cream 2%; gel 2, 2.5%; oint 2.5, 5%; liq 2.5%; soln 2, 4%; vis- cous 2%. (For infusion, see Table 20–10, page 637.) NOTES: Endotracheal doses should be diluted to 1–2 mL with NS; epinephrine may be added for local anesthesia to prolong effect and help decrease bleeding; do NOT use lidocaine with epineph- rine on the digits, ears, or nose because vasoconstriction may cause necrosis; for IV forms, ↓ dose with liver disease or CHF; dizziness, paresthesias, and convulsions associated with toxicity; see Table 22–7 (pages 631–634) for drug levels Lidocaine/Prilocaine (EMLA) COMMON USES: Topical anesthetic; adjunct to phlebotomy or invasive dermal procedures ACTIONS: Topical anesthetic DOSAGE: Adults. EMLA cream and anesthetic disc (1 g/10 cm2): Apply thick layer of cream 2–2.5 g to intact skin and cover with an occlusive dressing (eg, Tegaderm) for at least 1 h. Anesthetic disc: 1 g/10 cm2 for at least 1 h. Peds. Max dose: ≤3 mo or <5 kg: 1 g/10 cm2 for 1 h. 3–12 mo and >5 kg: 2 g/20 cm2 for 4 h. 1–6 y and »10 kg: 10 g/100 cm2 for 4 h. 7–12 y and >20 kg: 20 g/200 cm2 for 4 h SUPPLIED: Cream 2.5% lidocaine/2.5% prilocaine; anesthetic disc (1 g) NOTES: Not for ophth use; use with caution when risk of methemoglobinemia; longer contact time gives greater effect Lindane (Kwell) COMMON USES: Head lice,

crab lice, scabies ACTIONS: Ectoparasiticide and ovicide DOSAGE: Adults & Peds. Cream or lotion: Apply thin layer after bathing and leave in place for 8–12h (6–8 h for children, 6 h for infants), pour on laundry. Shampoo: Apply 30 mL and develop a lather with warm water for 4 min; comb out nits SUPPLIED: Lotion 1%; shampoo 1% NOTES: Caution with overuse; may be absorbed into blood; repeat in 7 d if necessary Linezolid (Zyvox) COMMON USES: Infections caused by gram+ bacteria, including vancomycin-resistant and methi- cillin-resistant strains ACTIONS: Unique action, binds ribosomal bacterial RNA; bacteriocidal for strep, bacteriostatic for enterococci and staph DOSAGE: 400–600 mg IV or PO q12h SUPPLIED: Inj 2 mg/mL; tabs 400, 600 mg; susp 100 mg/5 mL NOTES: Reversible MAO inhibitor; avoid foods containing tyramine; avoid cough and cold prod- ucts containing pseudoephedrine 22 562 Clinician’s Pocket Reference, 9th Edition Liothyronine (Cytomel) COMMON USES: Hypothyroidism ACTIONS: T3 replacement DOSAGE: Adults. Initial dose of 25 µg/24h, then titrate q 1–2 wk according to clinical response and TFT to maintenance of 25–100 µg/d PO. Myxedema coma: 25–50 µg IV. Peds. Initial dose of 5 µg/24h, then titrate by 5 µg/24h increments at 1–2-wk intervals; maintenance 25–75 µg/24h PO qd SUPPLIED: Tabs 5, 25, 50 µg; inj 10 µg/mL NOTES: ↓ Dose in elderly; monitor TFT Lisinopril (Prinivil, Zestril) COMMON USES: HTN, heart failure, and AMI ACTIONS: ACE inhibitor DOSAGE: 5–40 mg/24h PO qd–bid. AMI: 5 mg within 24h of MI, followed by 5 mg after 24h, 10 mg after 48 h, then 10 mg/d SUPPLIED: Tabs 2.5, 5, 10, 20, 30, 40 mg NOTES: Dizziness, headache, and cough common side effects; Do NOT use in PRG Lithium Carbonate (Eskalith, others) COMMON USES: Manic episodes of bipolar illness; maintenance therapy in recurrent disease ACTIONS: Effects shift toward intraneuronal metabolism of catecholamines DOSAGE: Adults. Acute mania: 600 mg PO tid or 900 mg SR bid. Maintenance: 300 mg PO tid–qid. Peds 6–12 y. 15–60 mg/kg/d in 3–4 ÷ doses SUPPLIED: Caps 150, 300, 600 mg; tabs 300 mg; SR tabs 300, 450 mg; syrup 300 mg/5 mL NOTES: Dosage must be titrated; follow serum levels (Table 22–7, pages 631–634); common side effects polyuria and tremor; contra in patients with severe renal impairment; Na retention or di- uretic use may potentiate toxicity Lodoxamide (Alomide Ophthalmic) COMMON USES: Seasonal allergic conjunctivitis ACTIONS: Stabilizes mast cells DOSAGE: Adults & Peds >2 y. 1–2 gtt in eye(s) qid up to 3 mo SUPPLIED: Soln 0.1% Lomefloxacin (Maxaquin) COMMON USES: UTI and lower respiratory tract infections caused by gram– bacteria; prophylaxis in transurethral procedures ACTIONS: Quinolone antibiotic; inhibits DNA gyrase DOSAGE: 400 mg/d PO SUPPLIED: Tabs 400 mg NOTES: May cause photosensitivity; renal dosage adjustment Lomustine (CCNU, CeeNu) COMMON USES: Hodgkin’s lymphoma and primary brain tumors ACTIONS: Nitrosourea alkylating agent DOSAGE: 130 mg/m2 single dose repeated q 6 wk SUPPLIED: Caps 10, 40, 100 mg; dose pack NOTES: Toxicity symptoms: Myelosuppression, renal injury, anorexia, nausea and vomiting, stom- atitis, pulmonary fibrosis, and hepatotoxicity. High lipid solubility translates into excellent penetra- tion into the CNS Loperamide (Imodium) COMMON USES: Diarrhea 22 ACTIONS: Slows intestinal motility 22 Commonly Used Medications 563 DOSAGE: Adults. Initially, 4 mg PO; then 2 mg after each loose stool, up to 16 mg/d. Peds. 0.4–0.8 mg/kg/24h PO ÷ q6–12h until diarrhea resolves or for 7 d max SUPPLIED: Caps 2 mg; tabs 2 mg; liq 1 mg/5 mL, 1 mg/mL NOTES: Do NOT use in acute diarrhea caused by Salmonella, Shigella, or C. difficile Loracarbef (Lorabid) COMMON USES: Infections caused by susceptible bacteria involving the upper and lower respira- tory tract, skin, bone, urinary tract, abdomen, and gynecologic system ACTIONS: 2nd-generation cephalosporin; inhibits cell wall synthesis DOSAGE: Adults. 200–400 mg PO bid. Peds. 7.5–15 mg/kg/d PO ÷ bid SUPPLIED: Caps 200, 400 mg; susp 125, 250 mg/5 mL NOTES: More gram (−) activity than 1st-generation cephalosporins Loratadine (Claritin) COMMON USES: Allergic rhinitis ACTIONS: Nonsedating antihistamine DOSAGE: 10 mg/d PO SUPPLIED: Tabs 10 mg; syrup 1 mg/mL NOTES: Take on an empty stomach Lorazepam (Ativan, others) [C-IV] COMMON USES: Anxiety and anxiety mixed with depression; preop sedation; control of status epilepticus; antiemetic ACTIONS: Benzodiazepine; antianxiety agent DOSAGE: Adults. Anxiety: 1–10 mg/d PO in 2–3 ÷ doses. Preop sedation: 0.05 mg/kg to a max of 4 mg IM 2 h before surgery. Insomnia: 2–4 mg PO hs. Status epilepticus: 4 mg/dose IV may be re- peated at 10–15-min intervals; usual total dose 8 mg. Antiemetic: 0.5–2 mg IV or PO q4–6h PRN. Peds. Status epilepticus: 0.05 mg/kg/dose IV repeated at 1–20-min intervals × 2 PRN. Antiemetic, 2–15 y old: 0.05 mg/kg (to 2 mg/dose) prior to chemotherapy SUPPLIED: Tabs 0.5, 1, 2 mg; soln, oral conc 2 mg/mL; inj 2, 4 mg/mL NOTES: ↓ Dose in elderly; do NOT administer IV faster than 2 mg/min or 0.05 mg/kg/min; may take up to 10 min to see effect when given IV Losartan (Cozaar) COMMON USES: HTN ACTIONS: Angiotensin II antagonist DOSAGE: 25–50 mg PO qd–bid SUPPLIED: Tabs 25, 50, 100 mg NOTES: Do NOT use in PRG; symptomatic hypotension may occur in patients on diuretics; dosage adjustment in elderly or hepatic impairment Lovastatin (Mevacor) COMMON USES: Hypercholesterolemia; to slow the progression of atherosclerosis ACTIONS: HMG-CoA reductase inhibitor DOSAGE: 20 mg/d PO with PM meal; may ↑ at 4-wk intervals to a max of 80 mg/d taken with meals SUPPLIED: Tabs 10, 20, 40 mg NOTES: Patient must maintain standard cholesterol-lowering diet throughout treatment; monitor LFT q 6 wk during the 1st year of therapy; headache and GI intolerance common; patient should promptly report any unexplained muscle pain, tenderness, or weakness; avoid concurrent use with gemfibrozil Lyme Disease Vaccine (Lymerix) COMMON USE: Prevention of Lyme disease ACTION: Provides active immunity against Borrelia burgdorferi 22 564 Clinician’s Pocket Reference, 9th Edition DOSAGE: 30 µg/0.5 mL IM administered at 0, 1, and 12 mo SUPPLIED: Vaccine 0.3 µg/0.5 mL Magaldrate (Riopan, Lowsium) COMMON USES: Hyperacidity associated with peptic ulcer, gastritis, and hiatal hernia ACTIONS: Low-Na antacid DOSAGE: 5–10 mL PO between meals and hs SUPPLIED: Susp NOTES: <0.3 mg Na/tab or tsp; do NOT use in renal insufficiency due to Mg content Magnesium Citrate COMMON USES: Vigorous bowel preparation; constipation ACTIONS: Cathartic laxative DOSAGE: Adults. 120–240 mL PO PRN. Peds. 0.5 mL/kg/dose, to a max of 200 mL PO SUPPLIED: Effervescent soln NOTES: Do NOT use in renal insufficiency or intestinal obstruction Magnesium Hydroxide (Milk of Magnesia) COMMON USES: Constipation ACTIONS: Saline laxative DOSAGE: Adults. 15–30 mL PO PRN. Peds. 0.5 mL/kg/dose PO PRN SUPPLIED: Tabs 311 mg, liq 400 mg/5 mL, 800 mg/5 mL NOTES: Do NOT use in renal insufficiency or intestinal obstruction Magnesium Oxide (Mag-Ox 400, others) COMMON USES: Replacement for low plasma levels ACTIONS: Mg supplementation DOSAGE: 400–800 mg/d ÷ qd–qid. (See Chapter 9) SUPPLIED: Caps 140 mg; tabs 400 mg NOTES: May cause diarrhea Magnesium Sulfate Used for emergency cardiac care (see Chapter 21) COMMON USES: Replacement for low plasma levels; refractory hypokalemia and hypocalcemia; preeclampsia and premature labor ACTIONS: Mg supplement DOSAGE: Adults. Supplement: 1–2 g IM or IV; repeat dosing based on response and continued hy- pomagnesemia. (See also Chapter 9.) Preeclampsia, premature labor: 4 g load then 1–4 g/h IV in- fusion. Peds. 25–50 mg/kg/dose IM or IV q4–6h for 3–4 doses; may repeat if hypomagnesemia persists SUPPLIED: Inj 100, 125, 250, 500 mg/mL; oral soln 500 mg/mL; granules 40 meq/5 g NOTES: ↓ Dose with low urine output or renal insufficiency Mannitol Used for emergency care (see Chapter 21) COMMON USES: Cerebral edema, oliguria, anuria, myoglobinuria ACTIONS: Osmotic diuretic DOSAGE: Adults. Diuresis: 0.2 g/kg/dose IV over 3–5 min; if no diuresis within 2 h, discontinue. Peds. Diuresis: 0.75 g/kg/dose IV over 3–5 min; if no diuresis within 2 h, discontinue. Adults & Peds. Cerebral edema: 0.25 g/kg/dose IV push, repeated at 5-min intervals PRN; ↑ incrementally to 1 g/kg/dose PRN for increased intracranial pressure SUPPLIED: Inj 5%, 10%, 15%, 20%, 25% 22 NOTES: Caution with CHF or volume overload 22 Commonly Used Medications 565 Maprotiline (Ludiomil) COMMON USES: Depressive neurosis, bipolar illness, major depressive disorder, and anxiety asso- ciated with depression ACTIONS: Tetracyclic antidepressant DOSAGE: 75–150 mg/d hs, to a max of 300 mg/d SUPPLIED: Tabs 25, 50, 75 mg NOTES: Contra with MAO inhibitors or seizure history; patients >60 y, give only 50–75 mg/d; anti- cholinergic side effects Mechlorethamine (Mustargen) COMMON USES: Hodgkin’s and non-Hodgkin’s lymphoma, cutaneous T-cell lymphoma (mycosis fungoides), lung cancer, CLL, CML, and malignant pleural effusions ACTIONS: Alkylating agent (bifunctional) DOSAGE: 0.4 mg/kg single dose or 0.1 mg/kg/d for 4 d; 6 mg/m2 1–2 ×/mo SUPPLIED: Inj 10 mg NOTES: Toxicity symptoms: Myelosuppression, thrombosis, or thrombophlebitis at inj site; tissue damage with extravasation (Na thiosulfate may be used topically to treat); nausea and vomiting; skin rash; amenorrhea; and sterility. High rates of sterility (especially in men) and secondary leukemia in patients treated for Hodgkin’s disease. Highly volatile; must be administered within 30–60 min of preparation Meclizine (Antivert) COMMON USES: Motion sickness; vertigo associated with diseases of the vestibular system ACTIONS: Antiemetic, anticholinergic, and antihistaminic properties DOSAGE: Adults & Peds >12 y. 25 mg PO tid–qid PRN SUPPLIED: Tabs 12.5, 25, 50 mg; chewable tabs 25 mg; caps 25, 30 mg NOTES: Drowsiness, dry mouth, and blurred vision common Medroxyprogesterone (Provera, Depot Provera, Cycrin) COMMON USES: Secondary amenorrhea and abnormal uterine bleeding caused by hormonal imbal- ance; endometrial cancer ACTIONS: Progestin supplement DOSAGE: Secondary amenorrhea: 5–10 mg/d PO for 5–10 d. Abnormal uterine bleeding: 5–10 mg/d PO for 5–10 d beginning on the 16th or 21st d of the menstrual cycle. Endometrial cancer: 400–1000 mg/wk IM SUPPLIED: Tabs 2.5, 5, 10 mg; depot inj 100, 150, 400 mg/mL NOTES: Contra with past thromboembolic disorders or with hepatic disease Megestrol Acetate (Megace) COMMON USES: Breast and endometrial cancers; appetite stimulant in cancer and HIV-related cachexia ACTIONS: Hormone; progesterone analogue DOSAGE: Cancer: 40–320 mg/d PO in ÷ doses. Appetite: 800 mg/d PO SUPPLIED: Tabs 20, 40 mg; soln 40 mg/mL NOTES: May induce DVT; do NOT abruptly discontinue therapy Meloxicam (Mobic) COMMON USES: Osteoarthritis ACTIONS: NSAID agent DOSAGE: 7.5–15 mg/d PO SUPPLIED: Tabs 7.5 mg NOTES: ↓ Dose in renal impairment 22 566 Clinician’s Pocket Reference, 9th Edition Melphalan [L-PAM] (Alkeran) COMMON USES: Multiple myeloma, breast cancer, testicular cancer, ovarian cancer, melanoma, and allogenic and ABMT in high doses ACTIONS: Alkylating agent (bifunctional) DOSAGE: (Per protocol) 9 mg/m2 or 0.25 mg/kg/d for 4–7 d, repeated at 4–6-wk intervals, or 1 mg/kg single dose once q 4–6 wk; 0.15 mg/kg/d for 5 d q 6 wk. High dose for high-risk multiple myeloma: Single dose 140 mg/m2.ABMT: 140–240 mg/m2 IV SUPPLIED: Tabs 2 mg; inj 50 mg NOTES: Toxicity symptoms: Myelosuppression (leukopenia and thrombocytopenia), secondary leukemia, alopecia, dermatitis, stomatitis, and pulmonary fibrosis; very rare hypersensitivity reac- tions Meperidine (Demerol) [C-II] COMMON USES: Relief of moderate to severe pain ACTIONS: Narcotic analgesic DOSAGE: Adults. 50–150 mg PO or IM q3–4h PRN. Peds. 1–1.5 mg/kg/dose PO or IM q3–4h PRN, up to 100 mg/dose SUPPLIED: Tabs 50, 100 mg; syrup 50 mg/mL; inj 10, 25, 50, 75, 100 mg/mL NOTES: 75 mg IM = 10 mg of morphine IM; beware of respiratory depression; do NOT use in renal failure; ↓ dose in elderly and renal impairment Meprobamate (Equanil, Miltown) [C-IV] COMMON USES: Short-term relief of anxiety ACTIONS: Mild tranquilizer; antianxiety DOSAGE: Adults. 400 mg PO tid–qid up to 2400 mg/d; SR 400–800 mg PO bid. Peds 6–12 y. 100–200 mg bid–tid; SR 200 mg bid SUPPLIED: Tabs 200, 400, 600 mg; SR caps 200, 400 mg NOTES: May cause drowsiness; adjust dose for renal impairment Mercaptopurine [6-MP] (Purinethol) COMMON USES: Acute leukemias of children and adults, 2nd-line Rx of CML and non-Hodgkin’s lymphoma, maintenance therapy of ALL in children, and immunosuppressant therapy for autoim- mune diseases (Crohn’s disease) ACTIONS: Antimetabolite; mimics hypoxanthine DOSAGE: 80–100 mg/m2/d or 2.5–5 mg/kg/d; maintenance 1.5–2.5 mg/kg/d SUPPLIED: Tabs 50 mg NOTES: Toxicity symptoms: Mild hematologic toxicity; uncommon GI toxicity, except mucositis, stomatitis, and diarrhea. Rash, fever, eosinophilia, jaundice, and hepatitis. Concurrent allopurinol therapy requires a 67–75% ↓ of 6-MP because of interference with metabolism by xanthine oxidase Meropenem (Merrem) COMMON USES: Serious infections caused by a wide variety of bacteria including intraabdominal and polymicrobial; bacterial meningitis ACTIONS: Carbapenem; inhibition of cell wall synthesis, a

β-lactam DOSAGE: Adults. 1 g IV q8h. Peds. 20–40 mg/kg IV q8h SUPPLIED: Inj NOTES: Adjust dose for renal function; less seizure potential than imipenem; beware of possible anaphylaxis Mesalamine [5-Amino salicylic acid] (Rowasa, Asacol, Pentasa) COMMON USES: Mild to moderate distal ulcerative colitis, proctosigmoiditis, or proctitis ACTIONS: Unknown; may topically inhibit prostaglandins DOSAGE: Retention enema qd hs or insert 1 supp bid. Oral: 800–1000 mg PO 3–4×/d 22 SUPPLIED: Tabs 400 mg; caps 250 mg; supp 500 mg; rectal susp 4 g/60 mL 22 Commonly Used Medications 567 Mesna (Mesnex) COMMON USES: ↓ Incidence of ifosfamide and cyclophosphamide-induced hemorrhagic cystitis ACTIONS: Antidote DOSAGE: 20% of the ifosfamide dose (+/–) or cyclophosphamide dose IV at 15 min prior to and 4 and 8 h after chemotherapy SUPPLIED: Inj 100 mg/mL Mesoridazine (Serentil) COMMON USES: Schizophrenia, acute and chronic alcoholism, and chronic brain syndrome ACTIONS: Phenothiazine antipsychotic DOSAGE: Initially, 25–50 mg PO or IV tid; ↑ to a max of 300–400 mg/d SUPPLIED: Tabs 10, 25, 50, 100 mg; oral conc 25 mg/mL; inj 25 mg/mL NOTES: Low incidence of extrapyramidal side effects Metaproterenol (Alupent, Metaprel) COMMON USES: Bronchodilator for asthma and reversible bronchospasm ACTIONS: Sympathomimetic bronchodilator DOSAGE: Adults. Inhal: 1–3 inhal q3–4h to a max of 12 inhal/24h; allow at least 2 min between inhal. Oral: 20 mg q6–8h. Peds. Inhal: 0.5 mg/kg/dose to a max of 15 mg/dose inhaled q4–6h by neb or 1–2 puffs q4–6h. Oral: 0.3–0.5 mg/kg/dose q6–8h SUPPLIED: Aerosol 75, 150 mg; soln for inhal 0.4%, 0.6% 5%; tabs 10, 20 mg; syrup 10 mg/ 5 mL NOTES: Fewer β1-effects than isoproterenol and longer acting Metaraminol (Aramine) COMMON USES: Prevention and Rx of hypotension due to spinal anesthesia ACTIONS: α-Adrenergic agent DOSAGE: Adults. Prevention: 2–10 mg IM q10–15min PRN. Rx: 0.5–5 mg IV bolus followed by IV inf of 1–4 mg/kg/min titrated to effect. Peds. Prevention: 0.1 mg/kg/dose IM PRN. Rx: 0.01 mg/kg IV bolus followed by IV inf of 5 mg/kg/min titrated to effect SUPPLIED: Injectable forms NOTES: Allow 10 min for max effect; employ other shock management techniques, eg, fluid resus- citation as needed; may cause cardiac arrhythmias Metaxalone (Skelaxin) COMMON USES: Relief of painful musculoskeletal conditions ACTIONS: Centrally acting skeletal muscle relaxant DOSAGE: 800 mg PO 3–4×/d SUPPLIED: Tabs 400 mg Metformin (Glucophage) COMMON USES: Type 2 DM ACTIONS: Decreases hepatic glucose production; ↓ intestinal absorption of glucose; improves in- sulin sensitivity DOSAGE: Initial dose of 500 mg PO bid; may ↑ to max dose 2500 mg/d SUPPLIED: Tabs 500, 850 mg NOTES: Administer with the AM and PM meals; may cause lactic acidosis; do NOT use if SCr >1.3 in females or >1.4 in males; withhold prior to and following IV contrast studies; contra in hypox- emic conditions, including acute CHF and sepsis Methadone (Dolophine) [C-II] COMMON USES: Severe pain; detoxification and maintenance of narcotic addiction ACTIONS: Narcotic analgesic 22 568 Clinician’s Pocket Reference, 9th Edition DOSAGE: Adults. 2.5–10 mg IM q 3–8h or 5–15 mg PO q8h; titrate as needed. Peds. 0.7 mg/kg/24h PO or IM ÷ q8h SUPPLIED: Tabs 5, 10, 40 mg; oral soln 5, 10 mg/5 mL; oral conc 10 mg/mL; inj 10 mg/mL NOTES: Equianalgesic with parenteral morphine; long half-life; ↑ slowly to avoid respiratory de- pression Methenamine (Hiprex, Urex, others) COMMON USES: Suppression or elimination of bacteriuria associated with chronic and recurrent UTI DOSAGE: Adults. Hippurate: 1 g bid, mandelate: 1 g qid pc and hs. Peds 6–12 y. Hippurate: 25–50 mg/kg/d ÷ bid. Mandelate: 50–75 mg/kg/d ÷ qid SUPPLIED: Methenamine hippurate (Hiprex, Urex): 1-g tabs. Methenamine mandelate: 500 mg/1 g EC tabs NOTES: Contra in patients with renal insufficiency, severe hepatic disease, and severe dehydration Methimazole (Tapazole) COMMON USES: Hyperthyroidism and preparation for thyroid surgery or radiation ACTIONS: Blocks the formation of T3 and T4 DOSAGE: Adults. Initial: 15–60 mg/d PO ÷ tid. Maintenance: 5–15 mg PO qd. Peds. Initial: 0.4–0.7 mg/kg/24h PO ÷ tid. Maintenance: 1⁄3–2⁄3 of the initial dose PO qd SUPPLIED: Tabs 5, 10 mg NOTES: Follow patient clinically and with TFT Methocarbamol (Robaxin) COMMON USES: Relief of discomfort associated with painful musculoskeletal conditions ACTIONS: Centrally acting skeletal muscle relaxant DOSAGE: Adults. 1.5 g PO qid for 2–3 d, then 1 g PO qid maintenance therapy; IV form rarely in- dicated. Peds. 15 mg/kg/dose may be repeated if necessary. (Recommended for tetanus only) SUPPLIED: Tabs 500, 750 mg; inj 100 mg/mL NOTES: Can discolor urine; may cause drowsiness or GI upset; contra with MyG Methotrexate (Folex, Rheumatrex) COMMON USES: ALL and AML, leukemic meningitis, trophoblastic tumors (chorioepithelioma, choriocarcinoma, chorioadenoma destruens, hydatidiform mole), breast cancer, Burkitt’s lym- phoma, mycosis fungoides, osteosarcoma, head and neck cancer, Hodgkin’s and non-Hodgkin’s lymphoma, lung cancer; psoriasis; and RA ACTIONS: Inhibits dihydrofolate reductase-mediated generation of tetrahydrofolate DOSAGE: Cancer, “conventional dose”: 15–30 mg PO or IV 1–2×/wk q 1–3 wk. “Intermediate dose”: 50–240 mg or 0.5–1 g/m2 IV once q 4 d to 3 wk. “High dose”: 1–12 g/m2 IV once q 1–3 wk; 12 mg/m2 (max 15 mg) IT, weekly until the CSF cell count returns to normal. RA: 7.5 mg/wk PO as a single dose or 2.5 mg q12h PO for 3 doses/wk SUPPLIED: Tabs 2.5 mg; inj 2.5, 25 mg/mL; preservative-free inj 25 mg/mL NOTES: Toxicity symptoms: Myelosuppression, nausea and vomiting, anorexia, mucositis, diarrhea, hepatotoxicity (transient and reversible; may progress to atrophy, necrosis, fibrosis, cirrhosis), rashes, dizziness, malaise, blurred vision, renal failure, pneumonitis, and, rarely, pulmonary fibro- sis. Chemical arachnoiditis and headache with IT delivery. High-dose therapy requires leucovorin rescue to prevent severe hematologic and mucosal toxicity (see page 559); monitor blood counts and MTX levels carefully Methoxamine (Vasoxyl) COMMON USES: Support, restoration, or maintenance of blood pressure during anesthesia; for ter- mination of some episodes of PSVT ACTIONS: α-Adrenergic DOSAGE: Adults. Anesthesia: 10–15 mg IM; if emergency, 3–5 mg slow IV push. PSVT: 10 mg by 22 slow IV push. Peds. 0.25 mg/kg/dose IM or 0.08 mg/kg/dose slow IV push 22 Commonly Used Medications 569 SUPPLIED: Injectable forms NOTES: IM dose requires 15 min to act; use 5–10 mg phentolamine locally in case of extravasation; interaction with MAO inhibitors and tricyclic antidepressants to potentiate methoxamine effect Methyldopa (Aldomet) COMMON USES: Essential HTN ACTIONS: Centrally acting antihypertensive DOSAGE: Adults. 250–500 mg PO bid–tid (max 2–3 g/d) or 250 mg–1 g IV q6–8h. Peds. 10 mg/kg/24h PO in 2–3 ÷ doses (max 40 mg/kg/24h ÷ q6–12h) or 5–10 mg/kg/dose IV q6–8h to total dose of 20–40 mg/kg/24h SUPPLIED: Tabs 125, 250, 500 mg; oral susp 50 mg/mL; inj 50 mg/mL NOTES: Do NOT use in the presence of liver disease; can discolor urine; initial transient sedation or drowsiness frequent Methylergonovine (Methergine) COMMON USES: Prevention and Rx postpartum hemorrhage caused by uterine atony ACTIONS: Ergotamine derivative DOSAGE: 0.2 mg IM after delivery of placenta, may repeat at 2–4-h intervals or 0.2–0.4 mg PO q6–12h for 2–7 d SUPPLIED: Injectable forms, 0.2 mg tabs NOTES: IV doses should be given over a period of not less than 1 min with frequent BP monitoring Methylprednisolone (Solu-Medrol) See Steroids (Table 22–5, see page 627). Metoclopramide (Reglan, Clopra, Octamide) COMMON USES: Relief of diabetic gastroparesis; symptomatic GERD; relief of cancer chemother- apy-induced nausea and vomiting ACTIONS: Stimulates motility of the upper GI tract and blocks dopamine in the chemoreceptor trig- ger zone DOSAGE: Adults. Diabetic gastroparesis: 10 mg PO 30 min ac and hs for 2–8 wk PRN; or same dose given IV for 10 d, then switch to PO. Reflux: 10–15 mg PO 30 min ac and hs. Antiemetic: 1–3 mg/kg/dose IV 30 min prior to antineoplastic agent, then q2h for 2 doses, then q3h for 3 doses. Peds. Reflux: 0.1 mg/kg/dose PO qid. Antiemetic: 1–2 mg/kg/dose IV on the same schedule as for adults SUPPLIED: Tabs 5, 10 mg; syrup 5 mg/5 mL; soln 10 mg/mL; inj 5 mg/mL NOTES: Dystonic reactions common with high doses; can be treated with IV diphenhydramine; can also be used to facilitate small bowel intubation and radiologic evaluation of the upper GI tract Metolazone (Mykrox, Zaroxolyn) COMMON USES: Mild to moderate essential HTN and edema of renal disease or cardiac failure ACTIONS: Thiazide-like diuretic; inhibits reabsorption of sodium in the distal tubules DOSAGE: Adults. HTN: 2.5–5 mg/d PO. Edema: 5–20 mg/d PO. Peds. 0.2–0.4 mg/kg/d PO ÷ q12h–qd SUPPLIED: Tabs 0.5, 2.5, 5, 10 mg NOTES: Monitor fluid and electrolyte status during treatment Metoprolol (Lopressor, Toprol XL) Used for emergency cardiac care (see also Chapter 21) COMMON USES: HTN, angina, and AMI ACTIONS: Competitively blocks β-adrenergic receptors, β1. DOSAGE: Angina: 50–100 mg PO bid. HTN: 100–450 mg/d PO. AMI: 5 mg IV × 3 doses, then 50 mg PO q6h × 48 h, then 100 mg PO bid SUPPLIED: Tabs 50, 100 mg; ER tabs 50, 100, 200 mg; inj 1 mg/mL 22 570 Clinician’s Pocket Reference, 9th Edition Metronidazole (Flagyl, Metrogel) COMMON USES: Amebiasis, trichomoniasis, C. difficile, H. pylori, anaerobic infections, and bacte- rial vaginosis ACTIONS: Interferes with DNA synthesis DOSAGE: Adults. Anaerobic infections: 500 mg IV q6–8h. Amebic dysentery: 750 mg/d PO for 5–10 d. Trichomoniasis: 250 mg PO tid for 7 d or 2 g PO in a single dose. C. difficile infection: 500 mg PO or IV q8h for 7–10 d. Vaginosis: 1 applicatorful intravaginally bid or 500 mg PO bid for 7 d. Acne rosacea and skin: Apply bid. Peds. Anaerobic infections: 15 mg/kg/24h PO or IV ÷ q6h. Amebic dysentery: 35–50 mg/kg/24h PO in 3 ÷ doses for 5–10 d SUPPLIED: Tabs 250, 500 mg; ER tabs 750 mg; caps 375 mg; topical lotion and gel 0.75%; gel, vaginal 0.75% (5 g/applicator 37.5 mg in 70 g tube) NOTES: For Trichomonas infections, also treat patient’s partner; ↓ in hepatic failure; no activity against aerobic bacteria; use in combination in serious mixed infections; may cause a disulfiram- like reaction; adjust dose in renal failure Metyrapone (Metopirone) COMMON USES: Diagnostic test for hypothalamic-pituitary ACTH function ACTIONS: Inhibits adrenocortical synthesis by blocking 11b-hydroxylase DOSAGE: Metyrapone test: Day 1: Control period, collect 24 h urine to measure 17-OHCS or 17-KSG. Day 2: ACTH test, administer 50 U of ACTH infused over 8 h and measure 24-h urinary steroids. Days 3–4: Rest period. Day 5: Administer metyrapone with milk or a snack. Adults. 750 mg PO q4h for 6 doses. Peds. 15 mg/kg q4h for 6 doses (min 250-mg dose). Day 6: Determine 24-h urinary steroids SUPPLIED: Tabs 250 mg (Limited availability in U.S.) NOTES: Normal 24-h urine 17-OHCS is 3–12 mg; following ACTH, it ↑ to 15–45 mg/24h; normal response to metyrapone is 2-fold to 4-fold increase in 17-OHCS excretion; drug interactions with phenytoin, cyproheptadine, and estrogens may lead to subnormal response Metyrosine (Demser) COMMON USES: Pheochromocytoma; short-term preop and long-term when surgery contraindi- cated ACTIONS: Tyrosine hydroxylase inhibitor DOSAGE: Adults & Peds >12 y. 250 mg PO qid, ↑ by 250–500 mg/d up to 4 g/d. Maintenance dose: 2–3 g/d ÷ qid SUPPLIED: 250 mg caps NOTES: Administer at least 5–7 d preop Mexiletine (Mexitil) COMMON USES: Suppression of symptomatic ventricular arrhythmias; diabetic neuropathy ACTIONS: Class IB antiarrhythmic DOSAGE: Administer with food or antacids; 200–300 mg PO q8h; do not exceed 1200 mg/d SUPPLIED: Caps 150, 200, 250 mg NOTES: Do NOT use in cardiogenic shock or 2nd- or 3rd-degree AV block if no pacemaker; may worsen severe arrhythmias; monitor LFT during therapy; drug interactions with hepatic enzyme in- ducers and suppressors requiring dosage changes Mezlocillin (Mezlin) COMMON USES: Infections caused by susceptible strains of gram (−) bacteria (including Kleb- siella, Proteus, E. coli, Enterobacter, P. aeruginosa, and Serratia) involving the skin, bone, respira- tory tract, urinary tract, abdomen, and septicemia ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults. 3 mg IV q4–6h. Peds. 200–300 mg/kg/d ÷ q4–6h SUPPLIED: Inj 22 NOTES: Often used in combination with aminoglycoside; adjust dosage for renal impairment 22 Commonly Used Medications 571 Miconazole (Monistat, others) COMMON USES: Severe systemic fungal infections, including coccidioidomycosis, candidiasis, Cryptococcus, etc; various tinea forms; cutaneous candidiasis; vulvovaginal candidiasis; tinea ver- sicolor ACTIONS: Fungicidal; alters permeability of the fungal cell membrane DOSAGE: Adults. Apply to affected area bid for 2–4 wk. Candidiasis: 600–1800 mg/day ÷ Q8h Intravaginally: Insert 1 applicatorful or supp hs for 7 d SUPPLIED: Topical cream 2%; lotion 2%; powder 2%; spray 2%; vaginal supp 100, 200 mg; vaginal cream 2%, IU forms NOTES: Antagonistic to

amphotericin B in vivo; rapid IV infusion may cause tachycardia or ar- rhythmias; may potentiate warfarin drug activity Midazolam (Versed) [C-IV] COMMON USES: Preoperative sedation, conscious sedation for short procedures, and induction of general anesthesia ACTIONS: Short-acting benzodiazepine DOSAGE: Adults. 1–5 mg IV or IM; titrate dose to effect. Peds. Conscious sedation: 0.08 mg/kg IM in a single dose. General anesthesia: 0.15 mg/kg IV followed by 0.05 mg/kg/dose q 2 min for 1–3 doses as needed to induce anesthesia SUPPLIED: Inj 1, 5 mg/mL; syrup 2 mg/mL NOTES: Monitor for respiratory depression; may produce hypotension in conscious sedation Mifepristone [RU 486] (Mifeprex) COMMON USES: Termination of intrauterine pregnancies of <49 d ACTIONS: Antiprogestin; increases prostaglandins, resulting in uterine contraction DOSAGE: Must be administered with 3 office visits: Day 1, three 200-mg tablets, PO; Day 3 if no abortion has occurred, give two 200-µg misoprostol PO; on or about day 14, verify termination of pregnancy SUPPLIED: Tabs 200 mg NOTES: Must be administered under physician supervision; can cause abdominal pain and 1–2 wk of uterine bleeding Miglitol (Glyset) COMMON USES: Type 2 DM ACTIONS: α-Glucosidase inhibitor; delays digestion of ingested carbohydrates DOSAGE: Initial 25 mg PO tid taken at the first bite of each meal; maintenance 50–100 mg tid with meals SUPPLIED: Tabs 25, 50, 100 mg NOTES: May be used alone or in combination with sulfonylureas Milrinone (Primacor) COMMON USES: CHF ACTIONS: Positive inotrope and vasodilator, with little chronotropic activity DOSAGE: Loading dose of 50 µg/kg, followed by cont inf of 0.375–0.75 µg/kg/min SUPPLIED: Inj 1 µg/mL NOTES: Carefully monitor fluid and electrolyte status; dosage adjustment in renal impairment Mineral Oil COMMON USES: Constipation ACTIONS: Emollient laxative DOSAGE: Adults. 5–45 mL PO PRN. Peds >6 y. 5–20 mL PO bid SUPPLIED: Liq 22 572 Clinician’s Pocket Reference, 9th Edition Minoxidil (Loniten, Rogaine) COMMON USES: Severe HTN; male and female pattern baldness ACTIONS: Peripheral vasodilator; stimulates vertex hair growth DOSAGE: Adults. Oral: 2.5–10 mg PO bid–qid. Topical: [Rogaine] Apply bid to the affected area. Peds. 0.2–1 mg/kg/24h ÷ PO q12–24h SUPPLIED: Tabs 2.5, 10 mg; topical soln (Rogaine) 2% NOTES: Pericardial effusion and volume overload may occur with oral use; hypertrichosis after chronic use Mirtazapine (Remeron) COMMON USES: Depression ACTIONS: Tetracyclic antidepressant, unrelated to tricyclics or MAOIs. DOSAGE: 15 mg PO hs, up to 45 mg/d hs SUPPLIED: Tabs 15, 30, 45 mg NOTES: Do NOT ↑ dose at intervals of less than 1–2 wk; may cause agranulocytosis Misoprostol (Cytotec) COMMON USES: Prevention of NSAID-induced gastric ulcers ACTIONS: Synthetic prostaglandin with both antisecretory and mucosal protective properties DOSAGE: 200 µg PO qid with meals SUPPLIED: Tabs 100, 200 µg NOTES: Do NOT take during PRG; can cause miscarriage with potentially dangerous bleeding; GI side effects common Mitomycin C (Mutamycin) COMMON USES: Adenocarcinomas of the stomach, pancreas, colon, and breast; non-small-cell lung cancer; head and neck cancer; cervical cancer; squamous cell carcinoma of the anus; and blad- der cancer (intravesically) ACTIONS: Alkylating agent; may also generate oxygen free radicals, which induce DNA strand breaks DOSAGE: 20 mg/m2 q 6–8 wk or 10 mg/m2 in combination with other myelosuppressive drugs; bladder cancer 20–40 mg in 40 mL of NS via a urethral catheter once/wk for 8 wk, followed by monthly treatments for 1 y SUPPLIED: Inj NOTES: Toxicity symptoms: Myelosuppression, which may persist up to 3–8 wk after a dose and may be cumulative (minimized by a lifetime dose <50–60 mg/m2), nausea and vomiting, anorexia, stomatitis, and renal toxicity. Microangiopathic hemolytic anemia (similar to hemolytic-uremic syndrome) with progressive renal failure. Venoocclusive disease of the liver, interstitial pneumonia, and alopecia (rare); extravasation reactions can be severe. Adjust dose in renal impairment Mitotane (Lysodren) COMMON USES: Palliative treatment of inoperable adrenal cortex carcinoma ACTIONS: Exact action unclear; induces mitochondrial injury in adrenocortical cells DOSAGE: 8–10 g/d in 3–4 ÷ doses (begin at 2 g/d with full glucocorticoid replacement therapy) SUPPLIED: Tabs 500 mg NOTES: Toxicity symptoms: Anorexia, nausea and vomiting, and diarrhea. Acute adrenal insuffi- ciency may be precipitated by physical stresses (shock, trauma, infection), in which case cortico- steroid replacement necessary. Allergic reactions (rare), visual disturbances, hemorrhagic cystitis, albuminuria, hematuria, HTN or hypotension, minor aches, and fever Mitoxantrone (Novantrone) COMMON USES: AML (with cytarabine), ALL, CML, breast and prostate cancer, non-Hodgkin’s lymphoma 22 ACTIONS: DNA-intercalating agent; inhibitor of DNA topoisomerase II 22 Commonly Used Medications 573 DOSAGE: 12 mg/m2/d for 3 d (ANLL induction), 12–14 mg/m2 q 3 wk (advanced solid tumors) SUPPLIED: Inj 20, 25, 30 mg NOTES: Toxicity symptoms: Myelosuppression, nausea and vomiting, stomatitis, alopecia (infre- quent), cardiotoxicity; cumulative dose not to exceed 160 mg/m2 in patients receiving mediastinal radiation therapy or 120 mg/m2 in patients receiving prior anthracycline therapy; dosage adjust- ment for hepatic failure may be warranted Mivacurium (Mivacron) COMMON USES: Adjunct to general anesthesia or mechanical ventilation ACTIONS: Nondepolarizing neuromuscular blocker DOSAGE: Adults. 0.15 mg/kg/dose IV; may need to repeat at 15-min intervals. Peds. 0.2 mg/kg/dose IV; may need to repeat at 10-min interval SUPPLIED: Inj 0.5, 2 mg/mL NOTES: Dosage adjustment in renal impairment Moexipril (Univasc) COMMON USES: HTN ACTIONS: ACE inhibitor DOSAGE: 7.5–30 mg in 1–2 ÷ doses administered 1 h ac SUPPLIED: Tabs 7.5, 15 mg; adjust dose in renal impairment Molindone (Moban) COMMON USES: Psychotic disorders ACTIONS: Piperazine phenothiazine DOSAGE: Adults. 50-75 mg/d, ↑ to 225 mg/d if necessary. Peds. 3–5 y: 1–2.5 mg/d in 4 ÷ doses. 5–12 y: 0.5–1.0 mg/kg/d in 4 ÷ doses SUPPLIED: Tabs 5, 10, 25, 50, 100 mg; conc 20 mg/mL Montelukast (Singulair) COMMON USES: Prophylaxis and Rx of chronic asthma ACTIONS: Leukotriene receptor antagonist DOSAGE: Adults >15 y. 10 mg/d PO taken in PM. Peds. 6–14 y: 5 mg/d PO taken in PM. 2–5 y: 4 mg/d PO taken in PM SUPPLIED: Tabs 10 mg; chewable tabs 4, 5 mg NOTES: NOT for acute asthma attacks Moricizine (Ethmozine) COMMON USES: Ventricular arrhythmias ACTIONS: Class I antiarrhythmic DOSAGE: 200–300 mg PO tid SUPPLIED: Tabs 200, 250, 300 mg Morphine (Roxanol, Duramorph, MS Contin, others) [C-II] Used for emergency cardiac care (see Chapter 21) COMMON USES: Relief of severe pain ACTIONS: Narcotic analgesic DOSAGE: Adults. Oral: 10–30 mg q4h PRN; SR tabs 30–60 mg q8–12h. IV/IM: 2.5–15 mg q2-6h. Peds. 0.1–0.2 mg/kg/dose IM/IV q2–4h PRN, to a max of 15 mg/dose SUPPLIED: Tabs 10, 15, 30 mg; SR tabs 15, 30, 60 mg; soln 10, 20, 100 mg; supp 5, 10, 20 mg; inj 2, 4, 5, 8, 10, 15 mg/mL; preservative-free inj 0.5, 1 mg/mL NOTES: Large number of narcotic side effects; may require scheduled dosing to relieve severe chronic pain. Duramorph and MS Contin commonly used SR forms 22 574 Clinician’s Pocket Reference, 9th Edition Moxifloxacin (Avelox) COMMON USES: Acute sinusitis, acute bronchitis, and community acquired pneumonia ACTIONS: Quinolone; inhibits DNA gyrase DOSAGE: 400 mg/d once SUPPLIED: Tabs 400 mg NOTES: Active against gram (−) bacteria and S. pneumoniae; interactions with Mg, Ca, Al and Fe containing products and Class IA and III antiarrhythmic agents Mupirocin (Bactroban) COMMON USES: Impetigo; eradication of MRSA nasal carrier state ACTIONS: Inhibits bacterial protein synthesis DOSAGE: Topical: Apply small amount to affected area. Nasal: Apply bid in the nostrils SUPPLIED: Oint 2%; cream 2% NOTES: Do NOT use concurrently with other nasal products Muromonab-CD3 [OKT3] (Orthoclone OKT3) COMMON USES: Acute rejection following organ transplantation ACTIONS: Blocks T-cell function DOSAGE: Adults. 5 mg/d IV for 10–14 d. Peds. 0.1 mg/kg/d for 10–14 d SUPPLIED: Inj 5 mg/5 mL NOTES: Murine antibody; may cause significant fever and chills after the first dose; requires close patient monitoring for anaphylaxis B or pulmonary edema Mycophenolate (CellCept) COMMON USES: Prevention of organ rejection following transplantation ACTIONS: Inhibits immunologically mediated inflammatory responses DOSAGE: 1 g PO bid SUPPLIED: Caps (as Mofetil) 250, 500 mg, inj 500 mg NOTES: Used in conjunction with corticosteroids and cyclosporine Nabumetone (Relafen) COMMON USES: Arthritis and pain ACTIONS: NSAID; inhibits prostaglandin synthesis DOSAGE: 1000–2000 mg/d ÷ qd–bid SUPPLIED: Tabs 500, 750 mg Nadolol (Corgard) COMMON USES: HTN and angina ACTIONS: Competitively blocks β-adrenergic receptors (β1 and β2) DOSAGE: 40–80 mg/d; up to 240 mg/d (angina) or 320 mg/d (HTN) may be needed SUPPLIED: Tabs 20, 40, 80, 120, 160 mg Nafcillin (Nallpen) COMMON USES: Infections caused by susceptible strains of Staphylococcus and Streptococcus ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults. 1–2 g IV q4–6h. Peds. 50–200 mg/kg/d ÷ q4–6h SUPPLIED: Inj NOTES: No adjustments for renal function Naftifine (Naftin) COMMON USES: Tinea cruris and tinea corporis ACTIONS: Antifungal antibiotic DOSAGE: Apply bid 22 SUPPLIED: 1% cream; gel 22 Commonly Used Medications 575 Nalbuphine (Nubain) COMMON USES: Moderate to severe pain; preop and obstetrical analgesia ACTIONS: Narcotic agonist–antagonist; inhibits ascending pain pathways DOSAGE: Adults. 10–20 mg IM or IV q4–6h PRN; max of 160 mg per d; single max dose, 20 mg. Peds. 0.2 mg/kg IV or IM to a max dose of 20 mg SUPPLIED: Inj 10, 20 mg/mL NOTES: Causes CNS depression and drowsiness; use with caution in patients receiving opiates Nalidixic Acid (NegGram) COMMON USES: UTI caused by susceptible strains of Proteus, Klebsiella, Enterobacter, and E. coli, but not Pseudomonas ACTIONS: Inhibits bacterial RNA and DNA synthesis DOSAGE: Adults. 1 g PO qid. Suppressive: 500 mg PO qid. Peds. 55 mg/kg/24h in 4 ÷ doses. Sup- pressive: 33 mg/kg/d in 4 ÷ doses SUPPLIED: Tabs 250 mg, 500 mg, 1 g; oral susp 250 mg/5 mL NOTES: Resistance emerges within 48 h in a significant percentage of trials; may enhance the effect of oral anticoagulants; may cause CNS adverse effects that reverse on discontinuation; decreased effect with concurrent use of antacids Naloxone (Narcan) Used for emergency care (see also Chapter 21) COMMON USES: Reversal of narcotic effect ACTIONS: Competitive narcotic antagonist DOSAGE: Adults. 0.4–2.0 mg IV, IM, or SC q 5 min; max total dose of 10 mg. Peds. 0.01–1.0 mg/kg/dose IV, IM, or SC; may repeat IV q 3 min for 3 doses PRN SUPPLIED: Inj 0.4, 1.0 mg/mL; neonatal inj 0.02 mg/mL NOTES: May precipitate acute withdrawal in addicts; if no response after 10 mg, suspect nonnar- cotic cause Naltrexone (Revia) COMMON USES: Alcoholism and narcotic addiction ACTIONS: Competitively binds to opioid receptors DOSAGE: 50 mg/d PO SUPPLIED: Tabs 50 mg NOTES: May cause hepatotoxicity; do NOT give until opioid-free for 7–10 d Naphazoline and Antazoline (Albalon-A Ophthalmic, others) Naphazoline and Pheniramine Acetate (Naphcon A) COMMON USES: Temporary relief from ocular redness and itching caused by allergy ACTIONS: Vasoconstrictor and antihistamine DOSAGE: 1–2 gtt up to 4×/d SUPPLIED: Soln 15 mL NOTES: Contra in those with glaucoma, children <6 y, and with contact lens use Naproxen (Aleve [OTC], Naprosyn, Anaprox) COMMON USES: Arthritis and pain ACTIONS: NSAID; inhibits prostaglandin synthesis DOSAGE: Adults & Peds >12 y. 200–500 mg bid–tid, to a max of 1500 mg/d SUPPLIED: Tabs 200 [OTC], 250, 375, 500 mg; DR tabs 375, 500 mg; susp 125 mg/5 mL NOTES: ↓ Dose in hepatic impairment Naratriptan (Amerge) COMMON USES: Acute migraine attacks ACTIONS: Serotonin 5-HT1 receptor antagonist 22 576 Clinician’s Pocket Reference, 9th Edition DOSAGE: 1–2.5 mg PO once; may be repeated once in 4 h SUPPLIED: Tabs 1, 2.5 mg NOTES: Contra in persons with severe renal impairment; adjust dose in renal dysfunction; avoid in angina, ischemic heart disease, uncontrolled HTN, and ergot administration Nedocromil (Tilade) COMMON USES: Mild to moderate asthma ACTIONS: Antiinflammatory agent DOSAGE: 2 inhal 4×/d SUPPLIED: Met-dose inhaler Nefazodone (Serzone) COMMON USES: Depression ACTIONS: Inhibits neuronal uptake of serotonin and norepinephrine DOSAGE: Initially, 100 mg PO bid; usual effective range is 300–600 mg/d in 2 ÷ doses SUPPLIED: Tabs 100, 150, 200, 250 mg NOTES: May cause postural hypotension and allergic reactions Nelfinavir (Viracept) COMMON USES: HIV infection ACTIONS: Protease inhibitor; results in formation of immature, noninfectious virion DOSAGE: Adults. 750 mg PO tid or 1250 mg PO bid. Peds. 20–30 mg/kg PO tid SUPPLIED: Tabs 250 mg; oral powder NOTES: Food necessary to increase absorption; interacts with St. John’s wort Neomycin, Bacitracin and Polymyxin B (Neosporin Ointment) (see Bacitracin, Neomycin and Polymyxin, page 502) Neomycin, Colistin, and Hydrocortisone (Cortisporin-TC Otic Drops) Neomycin, Colistin, Hydrocortisone, and Thonzonium (Cortisporin-TC Otic Suspension) COMMON USES: External otitis, infections of mastoidectomy and fenestration cavities ACTIONS: Antibiotic and antiinflammatory DOSAGE: Adults.4–5 gtt in the ear(s) tid–qid. Peds. 3–4 gtt in ear(s) tid–qid SUPPLIED: Otic gtt and susp Neomycin and Dexamethasone (Neo-Dexameth Ophthalmic, NeoDecadron

Ophthalmic) COMMON USES: Steroid responsive inflammatory conditions of the cornea, conjunctiva, lid, and anterior segment ACTIONS: Antibiotic with antiinflammatory corticosteroid DOSAGE: 1–2 gtt in eye(s) q3–4h or thin coat tid–qid until response observed, then reduce dose to qd SUPPLIED: Cream neomycin 0.5%/dexamethasone 0.1%; oint neomycin 0.35%/dexamethasone 0.05%; soln neomycin 0.35%/dexamethasone 0.1% Neomycin, Polymyxin B (Neosporin Cream) COMMON USES: Infection in minor cuts, scrapes, and burns ACTIONS: Bactericidal antibiotic DOSAGE: Apply bid–qid SUPPLIED: Cream neomycin 3.5 mg/polymyxin B 10,000 U/g 22 NOTES: Different from Neosporin oint (See page 502) 22 Commonly Used Medications 577 Neomycin, Polymyxin-B and Dexamethasone, (Maxitrol) COMMON USES: Steroid-responsive ocular conditions with bacterial infection ACTIONS: Antibiotic with antiinflammatory corticosteroid DOSAGE: 1–2 gtt in eye(s) q4–6h; apply oint in eye(s) 3–4×/d SUPPLIED: Oint neomycin sulfate 3.5 mg/ polymyxin B sulfate 10,000 U/dexamethasone 0.1%/g; susp identical/5 mL NOTES: Should be used under supervision of ophthalmologist Neomycin, Polymyxin Bladder Irrigant COMMON USES: Continuous irrigant for prophylaxis against bacteriuria and gram– bacteremia as- sociated with indwelling catheter use ACTIONS: Bactericidal antibiotic DOSAGE: 1-mL irrigant added to 1 L of 0.9% NaCl; continuous irrigation of the bladder with 1–2 L of soln/24h SUPPLIED: Ampules 1, 20 mL NOTES: Potential for bacterial or fungal superinfection; slight possibility for neomycin-induced ototoxicity or nephrotoxicity Neomycin, Polymyxin, and Hydrocortisone (Cortisporin Ophthalmic and Otic) COMMON USES: Ocular and otic bacterial infections ACTIONS: Antibiotic and antiinflammatory DOSAGE: Otic: 3–4 gtt in the ear(s) 3–4×/d. Ophth: Apply a thin layer to the eye(s) or 1 gt 1–4×/d SUPPLIED: Otic susp; ophth soln; ophth oint Neomycin, Polymyxin-B and Prednisolone (Poly-Pred Opthalmic) COMMON USES: Steroid-responsive ocular conditions with bacterial infection ACTIONS: Antibiotic and antiinflammatory DOSAGE: 1–2 gtt in eye(s) q4–6h; apply oint in eye(s) 3–4×/d SUPPLIED: Susp, neomycin 0.35%/polymyxin B 10,000 U/prednisolone 0.5%/mL NOTES: Should be used under supervision of ophthalmologist Neomycin Sulfate COMMON USES: Hepatic coma and preoperative bowel preparation ACTIONS: Aminoglycoside; suppresses GI bacterial flora DOSAGE: Adults. 3–12 g/24h PO in 3–4 ÷ doses. Peds. 50–100 mg/kg/24h PO in 3–4 ÷ dose SUPPLIED: Tabs 500 mg; oral soln 125 mg/5 mL NOTES: Part of the Condon bowel prep Nevirapine (Viramune) COMMON USES: HIV infection ACTIONS: Nonnucleoside reverse transcriptase inhibitor DOSAGE: Adults. Initially 200 mg/d for 14 d; then 200 mg bid. Peds. <8 y: 4 mg/kg/d for 14 d; then 7 mg/kg bid. >8 y: 4 mg/kg/d for 14 d; then 4 mg/kg bid SUPPLIED: Tabs 200 mg; susp 50 mg/5 mL NOTES: May cause life-threatening rash; give without regard to food Niacin (Nicolar) COMMON USES: Adjunctive therapy in patients with significant refractory hyperlipidemia ACTIONS: Inhibits lipolysis; decreases esterification of triglycerides; increases lipoprotein lipase activity DOSAGE: 1–6 g tid; max of 9 g/d SUPPLIED: SR caps 125, 250, 300, 400, 500 mg; tabs 25, 50, 100, 250, 500 mg; SR tabs 150, 250, 500, 750 mg; elixir 50 mg/5 mL NOTES: Upper body and facial flushing and warmth following dose; may cause GI upset 22 578 Clinician’s Pocket Reference, 9th Edition Nicardipine (Cardene) COMMON USES: Chronic stable angina and HTN; prophylaxis of migraine ACTIONS: Ca channel-blocker DOSAGE: Oral: 20–40 mg PO tid. SR: 30–60 mg PO bid. IV: 5 mg/h IV cont inf; ↑ by 2.5 mg/h q 15 min to max 15 mg/h SUPPLIED: Caps 20, 30 mg; SR caps 30, 45, 60 mg; inj 2.5 mg/mL NOTES: Oral-to-IV conversion: 20 mg tid = 0.5 mg/h, 30 mg tid = 1.2 mg/h, 40 mg tid = 2.2 mg/h; adjust dose in renal or hepatic impairment Nicotine Gum (Nicorette, Nicorette DS) COMMON USES AND ACTIONS: See Nicotine, Transdermal DOSAGE: 9–12 pieces/d PRN. Max 30 pieces/d SUPPLIED: 2 mg (96 pieces/box); Nicorette DS has 4 mg/piece NOTES: Patients must stop smoking and perform behavior modification for max effect Nicotine Nasal Spray (Nicotrol NS) COMMON USES: Aid to smoking cessation for the relief of nicotine withdrawal ACTIONS: Provides systemic delivery of nicotine DOSAGE: 0.5 mg/actuation; 1–2 sprays/h, not to exceed 10 sprays/h. SUPPLIED: Nasal inhaler 10 mg/mL NOTES: Patients must stop smoking and perform behavior modification for max effect Nicotine, Transdermal (Habitrol, Nicoderm, Nicotrol, Prostep) COMMON USES: Aid to smoking cessation for the relief of nicotine withdrawal ACTIONS: Provides systemic delivery of nicotine DOSAGE: Individualized to the patient’s needs; apply 1 patch (14–22 mg/d), and taper over 6 wk SUPPLIED: Habitrol and Nicoderm 7, 14, 21 mg of nicotine/24h; Nicotrol 5, 10, 15 mg/24h; ProStep 11, 22 mg/24h NOTES: Nicotrol to be worn for 16 h to mimic smoking patterns; others worn for 24 h; patients must stop smoking and perform behavior modification for max effect Nifedipine (Procardia, Procardia Xl, Adalat, Adalat CC) COMMON USES: Vasospastic or chronic stable angina and HTN; tocolytic ACTIONS: Ca channel-blocker DOSAGE: Adults. SR tabs 30–90 mg/d. Tocolysis: 10–20 mg PO q4–6h. Peds. 0.6–0.9 mg/kg/24h ÷ tid–qid SUPPLIED: Caps 10, 20 mg; SR tabs 30, 60, 90 mg NOTES: Headaches common on initial treatment; reflex tachycardia may occur with regular release dosage forms; Adalat CC and Procardia XL are NOT interchangeable; SL administration NOT ad- visable Nilutamide (Nilandron) COMMON USES: Combination with surgical castration for the treatment of metastatic prostate can- cer ACTIONS: Nonsteroidal antiandrogen DOSAGE: 300 mg/d in ÷ doses for the first 30 d, then 150 mg/d SUPPLIED: 50-, 150-mg tabs NOTES: Toxicity symptoms: Hot flashes, loss of libido, impotence, diarrhea, nausea, vomiting, gy- necomastia, hepatic dysfunction (follow LFTs), and interstitial pneumonitis Nimodipine (Nimotop) COMMON USES: Prevention of vasospasm following subarachnoid hemorrhage ACTIONS: Ca channel-blocker 22 DOSAGE: 60 mg PO q4h for 21 d 22 Commonly Used Medications 579 SUPPLIED: Caps 30 mg NOTES: Contents of caps may be extracted and administered down a NG tube if caps cannot be swallowed whole; dosage adjustment in hepatic failure Nisoldipine (Sular) COMMON USES: HTN ACTIONS: Ca channel-blocker DOSAGE: 10–60 mg/d PO SUPPLIED: ER tabs 10, 20, 30, 40 mg NOTES: Do NOT take with grapefruit juice or high-fat meal; ↓ starting doses in elderly or hepatic impairment Nitrofurantoin (Macrodantin, Furadantin, Macrobid) COMMON USES: Prevention and Rx UTI ACTIONS: Bacteriostatic; interferes with carbohydrate metabolism DOSAGE: Adults. Suppression: 50–100 mg/d PO. Rx: 50–100 mg PO qid. Peds. 5–7 mg/kg/24h in 4 ÷ doses SUPPLIED: Caps and tabs 50, 100 mg; SR caps [Macrobid] 100 mg; susp 25 mg/5 mL NOTES: GI side effects common; should be taken with food, milk, or antacid; macrocrystals (Macrodantin) cause less nausea than other forms of the drug; avoid if CrCl <50 mL/min Nitroglycerin (Nitrostat, Nitrolingual, Nitro-Bid Ointment, Nitro-Bid IV, Nitrodisc, Transderm-Nitro, others) Used for emergency cardiac care (see Chapter 21) COMMON USES: Angina pectoris, acute and prophylactic therapy, CHF, BP control ACTIONS: Relaxation of vascular smooth muscle DOSAGE: Adults. SL: 1 tab q 5 min SL PRN for 3 doses. Translingual: 1–2 met-doses sprayed onto the oral mucosa q3–5 min, max 3 doses. Oral: 2.5–9 mg tid. IV: 5–20 µg/min, titrated to effect. Topical: Apply 1–2 in. of oint to the chest wall q6h, then wipe off at night. TD: 5–20-cm patch qd. Peds. 1 µg/kg/min IV, titrated to effect SUPPLIED: SL tabs 0.3, 0.4, 0.6 mg; translingual spray 0.4 mg/dose; SR caps 2.5, 6.5, 9, 13 mg; SR tabs 2.6, 6.5, 9.0 mg; inj 0.5, 5, 10 mg/mL; oint 2%; TD patches 2.5, 5, 7.5, 10, 15 mg/24h; buccal CR 1, 2, 3 mg NOTES: Tolerance to nitrates develops with chronic use after 1–2 wk; can be avoided by providing a nitrate-free period each day; use shorter-acting nitrates tid, and remove long-acting patches and oint before hs to prevent development of tolerance. (See Table 20–10, page 637.) Nitroprusside (Nitropress) COMMON USES: Hypertensive emergency, aortic dissection, and pulmonary edema ACTIONS: Reduces systemic vascular resistance DOSAGE: Adults & Peds. 0.5–10 µg/kg/min IV inf, titrated to desired effect; usual dose 3 µg/kg/min SUPPLIED: Inj 10 mg/mL, 25 mg/mL NOTES: Thiocyanate, the metabolite, excreted by the kidney; thiocyanate toxicity occurs at plasma levels of 5–10 mg/dL; if used to treat aortic dissection; use β-blocker concomitantly. (See Table 20–10, page 637.) Nizatidine (Axid) COMMON USES: Duodenal ulcers, GERD, and heartburn ACTIONS: H2-receptor antagonist DOSAGE: Active ulcer: 150 mg PO bid or 300 mg PO hs; maintenance 150 mg PO hs. GERD: 150 mg PO bid; maintenance PO hs. Heartburn: 75 mg PO bid SUPPLIED: Caps 75, 150, 300 mg NOTES: Dosage adjustment in renal impairment 22 580 Clinician’s Pocket Reference, 9th Edition Norepinephrine (Levophed) Used for emergency cardiac care (see Chapter 21) COMMON USES: Acute hypotensive states ACTIONS: Peripheral vasoconstrictor acting on both the arterial and venous beds DOSAGE: Adults. 8–12 µg/min IV, titrated to desired effect. Peds. 0.05–0.1 mg/kg/min IV, titrated to desired effect SUPPLIED: Inj 1 mg/mL NOTES: Correct blood volume depletion as much as possible prior to initiation of vasopressor ther- apy; drug interaction with tricyclic antidepressants leading to severe profound HTN; infuse into large vein to avoid extravasation; phentolamine 5–10 mg/10 mL NS injected locally as an antidote to extravasation. (See Table 20–10, page 637.) Norfloxacin (Noroxin) COMMON USES: Complicated and uncomplicated UTI caused by a wide variety of gram (−) bacte- ria, prostatitis, and infectious diarrhea ACTIONS: Quinolone, inhibits DNA gyrase DOSAGE: Adults. 400 mg PO bid. Gonorrhea: 800 mg as single dose. Conjunctivitis: 1–2 gtt qid SUPPLIED: Tabs 400 mg; ophth soln 0.3% NOTES: Do NOT use in PRG; drug interactions with antacids, theophylline, and caffeine; good con- centrations in the kidney and urine, poor blood levels; do NOT use for urosepsis; dosage adjust- ment in renal impairment Norgestrel (Ovrette) COMMON USES: Contraceptive ACTIONS: Prevent follicular maturation and ovulation DOSAGE: 1 tab/d; begin day 1 of menses SUPPLIED: Tabs 0.075 mg NOTES: Progestin-only products have higher risk of failure in prevention of pregnancy Nortriptyline (Aventyl, Pamelor) COMMON USES: Endogenous depression ACTIONS: Tricyclic antidepressant; increases the synaptic concentrations of serotonin and/or norep- inephrine in the CNS DOSAGE: Adults. 25 mg PO tid–qid; doses >150 mg/d NOT recommended. Elderly: 10–25 mg hs. Peds. 6–7 y: 10 mg/d. 8–11 y: 10–20 mg/d. >11 y: 25–35 mg/d SUPPLIED: Caps 10, 25, 50, 75 mg; soln 10 mg/5 mL NOTES: Many anticholinergic side effects, including blurred vision, urinary retention, and dry mouth; max effect seen after 2 wk of therapy Nystatin (Mycostatin, Nilstat, others) COMMON USES: Mucocutaneous Candida infections (thrush, vaginitis) ACTIONS: Alters membrane permeability DOSAGE: Adults. Oral: 400,000–600,000 U PO “swish and swallow” qid. Vaginal: 1 tab vaginally hs for 2 wk. Topical: Apply bid–tid to the affected area. Peds. Infants: 200,000 U PO q6h. Chil- dren: See Adult dosage SUPPLIED: Oral susp 100,000 U/mL; oral tabs 500,000 U; troches 200,000 U; vaginal tabs 100,000 U; topical cream and oint 100,000 U/g NOTES: Not absorbed orally; therefore, NOT effective for systemic infections Octreotide (Sandostatin) COMMON USES: Suppresses or inhibits severe diarrhea associated with carcinoid and neuroen- docrine tumors of the intestinal tract; bleeding esophageal varices ACTIONS: Long-acting peptide that mimics the natural hormone somatostatin 22 22 Commonly Used Medications 581 DOSAGE: Adults. 100–600 µg/d SC in 2–4 ÷ doses; initiate at 50 µg qd–bid. Peds. 1–10 µg/kg/24h SC in 2–4 ÷ doses SUPPLIED: Inj 0.05, 0.1, 0.2, 0.5, 1 mg/mL NOTES: May cause nausea, vomiting, and abdominal discomfort Ofloxacin (Floxin, Ocuflox Ophthalmic) COMMON USES: Infections of the lower respiratory tract, skin and skin structure, and urinary tract, prostatitis, uncomplicated gonorrhea, and Chlamydia infections; topical for bacterial conjunctivitis; acute otitis media in children >1 y tympanostomy tubes; otitis externa in adults and children >1 y; if perforated ear drum >12 y ACTIONS: Bactericidal; inhibits DNA gyrase DOSAGE: Adults. 200–400 mg PO bid or IV q12h. Adults & Peds. >1 y: Ophth 1–2 gtt in eye(s) q2–4h for 2 d, then qid for 5 more d. Peds. Do NOT administer systemically in children <18 y. Peds 1–12 y: Otic 5 gtt in ear(s) bid for 10 d. Adults & Peds >12 y: Otic 10 gtt in ear(s) bid for 10 d SUPPLIED: Tabs 200, 300, 400 mg; inj 20, 40 mg/mL; ophth 0.3% NOTES: May cause nausea and vomiting, diarrhea, insomnia, and headache; drug interactions with antacids, sucralfate, and aluminum-, calcium-, magnesium-, iron-, or zinc-containing products de- crease absorption; may increase theophylline levels; dosage adjustment in renal impairment; ophth form used for ears Olanzapine (Zyprexa) COMMON USES: Psychotic disorders ACTIONS: Dopamine and serotonin antagonist DOSAGE: ↑ to max of 20 mg/d SUPPLIED: Tabs 5, 7.5, 10 mg NOTES: May take many weeks to titrate to therapeutic dose; cigarette smoking will decrease levels Olsalazine (Dipentum) COMMON

USES: Maintenance of remission of ulcerative colitis ACTIONS: Topical antiinflammatory activity DOSAGE: 500 mg PO bid SUPPLIED: Caps 250 mg NOTES: Take with food; may cause diarrhea Omeprazole (Prilosec) COMMON USES: Duodenal and gastric ulcers, Zollinger–Ellison syndrome, GERD, and H. pylori infections ACTIONS: Proton-pump inhibitor DOSAGE: 20–40 mg PO qd–bid SUPPLIED: Caps 10, 20, 40 mg NOTES: Combination (ie, antibiotic) therapy necessary for H. pylori infection Ondansetron (Zofran) COMMON USES: Prevention of nausea and vomiting associated with cancer chemotherapy and postoperative nausea and vomiting ACTIONS: Serotonin receptor antagonist DOSAGE: Adults & Peds. Chemotherapy: 0.15 mg/kg/dose IV prior to chemotherapy, then repeated 4 and 8 h after the first dose or 4–8 mg PO tid; administer the first dose 30 min prior to chemother- apy. Adults. Postop: 4 mg IV immediately before induction of anesthesia or postop SUPPLIED: Tabs 4, 8 mg; inj 2 mg/mL NOTES: May cause diarrhea and headache; administer on a schedule, NOT PRN 22 582 Clinician’s Pocket Reference, 9th Edition Oprelvekin (Neumega) COMMON USES: Prevention of severe thrombocytopenia due to chemotherapy ACTIONS: Promotes proliferation and maturation of megakaryocytes DOSAGE: Adults. 50 µg/kg/d SC for 10–21 d. Peds. 75–100 µg/kg/d SC for 10–21 d SUPPLIED: Inj NOTES: Interleukin-11 Oral Contraceptives,Biphasic, Monophasic, Triphasic, Progestin Only (see Table 22–3, pages 623–625) COMMON USES: Birth control and regulation of anovulatory bleeding ACTIONS: Birth Control: Suppresses LH surge, prevents ovulation, progestins thicken cervical mu- cous, inhibits fallopian tubule cilia, ↓ endometrial thickness and hence ↓ chances of fertilization. Anovulatory bleeding: Cyclic hormones mimic the body’s natural cycle and help regulate the en- dometrial lining, resulting in regular bleeding q 28 d; may also reduce uterine bleeding and dys- menorrhea DOSAGE: 28-d cycle pills taken qd. 21-d cycle pills taken qd, no pills taken during the last 7 d of the cycle (during the menstrual period) SUPPLIED: 28-d cycle pills (21 hormonally active pills + 7 placebo/Fe supplementation). 21-d cycle pills (21 hormonally active pills). See Table 22–3, page 000 NOTES: Taken correctly, 99.9% effective for preventing pregnancy, but do not protect against STD; encourage use of additional barrier contraceptive. Over long periods can ↓ risk of ectopic preg- nancy, benign breast disease, and future development of ovarian, and uterine cancer. Absolute con- tra: Undiagnosed abnormal vaginal bleeding, pregnancy, estrogen-dependent malignancy, hypercoagulation disorders, liver disease, and smokers >35 y. Relative contra: Migraine headaches, HTN, diabetes, sickle cell disease, and gallbladder disease. Rx for menstrual cycle control: Start with a monophasic pill. Pill must be taken for 3 mo before switching to another brand. Abnormal bleeding continues, changed to higher estrogen dose pill. Rx for birth control: Choose pill with the most beneficial side effect profile for particu- lar patient. Side effects numerous and due to symptoms of estrogen excess or progesterone deficiency. Because each pill’s side effect profile is unique (found in package insert), Rx may be tailored to specific patient. Common side effects: Intramenstrual bleeding, oligo- menorrhea, amenorrhea, increased appetite/weight gain, loss of libido, fatigue, depression, mood swings, mastalgia, headaches, melasma, increase vaginal discharge, acne/greasy skin, corneal edema, nausea Orphenadrine (Norflex) COMMON USES: Muscle spasms ACTIONS: Central atropine-like effects cause indirect skeletal muscle relaxation, euphoria, and analgesia DOSAGE: 100 mg PO bid, 60 mg IM/IV q12h SUPPLIED: Tabs 100 mg; SR tabs 100 mg; inj 30 mg/mL Oseltamivir (Tamiflu) COMMON USES: Influenza A and B ACTIONS: Inhibition of viral neuraminidase DOSAGE: 75 mg bid for 5 d SUPPLIED: Caps 75 mg NOTES: Initiate within 48 h of symptom onset; ↓ dose in renal impairment Oxacillin (Bactocill, Prostaphlin) COMMON USES: Infections caused by susceptible strains of S. aureus and Streptococcus ACTIONS: Bactericidal; inhibits cell wall synthesis 22 22 Commonly Used Medications 583 DOSAGE: Adults. 1–2 mg IV q4–6h. Peds. 150–200 mg/kg/d IV q4–6h SUPPLIED: Inj; caps 250, 500 mg; soln 250 mg/5 mL Oxaprozin (Daypro) COMMON USES: Arthritis and pain ACTIONS: NSAID; inhibits prostaglandin synthesis DOSAGE: 600–1200 mg/d SUPPLIED: Caplets 600 mg Oxazepam (Serax) [C] COMMON USES: Anxiety, acute alcohol withdrawal, and anxiety with depressive symptoms ACTIONS: Benzodiazepine DOSAGE: Adults. 10–15 mg PO tid–qid; severe anxiety and alcohol withdrawal may require up to 30 mg qid. Peds. 1 mg/kg/d in ÷ doses SUPPLIED: Caps 10, 15, 30 mg; tabs 15 mg NOTES: One of the metabolites of diazepam (Valium); avoid abrupt discontinuation Oxcarbazepine (Trileptal) COMMON USES: Partial seizures ACTIONS: Produce blockage of voltage-sensitive Na channels, resulting in stabilization of hyperex- cited neural membranes DOSAGE: Adults. 300 mg bid, ↑ dose weekly to a usual dose of 1200–2400 mg/d. Peds. 8–10 mg/kg bid, NOT to exceed 600 mg/d; ↑ dose weekly to target maintenance dose SUPPLIED: Tabs 150, 300, 600 mg NOTES: May cause clinically significant hyponatremia; possible cross-sensitivity to carbamazepine Oxiconazole (Oxistat) COMMON USES: Tinea pedis, tinea cruris, and tinea corporis ACTIONS: Antifungal antibiotic DOSAGE: Apply bid SUPPLIED: 1% Cream; lotion Oxybutynin (Ditropan, Ditropan XL) COMMON USES: Symptomatic relief of urgency, nocturia, and incontinence associated with neuro- genic or reflex neurogenic bladder ACTIONS: Direct antispasmodic effect on smooth muscle; increases bladder capacity DOSAGE: Adults & Peds > 5 y. 5 mg PO tid–qid. Adults. ER 5 mg PO qd; ↑ to 30 mg/d PO, (5 and 10 mg/tab). Peds 1–5 y. 0.02 mg/kg/dose bid–qid (syrup 5 mg/5 mL) SUPPLIED: Tabs 5 mg; ER tabs 5, 10, 15 mg; syrup 5 mg/5 mL NOTES: Anticholinergic side effects Oxycodone [Dihydrohydroxycodeinone] (OxyContin, OxyIR, Roxicodone) [C-II] COMMON USES: Moderate to severe pain, normally used in combination with nonnarcotic anal- gesics ACTIONS: Narcotic analgesic DOSAGE: Adults. 5 mg PO q6h PRN. Peds. 6–12 y: 1.25 mg PO q6h PRN. >12 y: 2.5 mg q6h PRN SUPPLIED: Immediate release caps (OxyIR) 5 mg; tabs (Percolone) 5 mg tabs; CR (OxyContin) 10, 20, 40, 80 mg; liq 5 mg/5 mL; soln conc 20 mg/mL NOTES: Usually prescribed in combination with acetaminophen or aspirin; OxyContin useful for chronic cancer pain Oxycodone and Acetaminophen (Percocet, Tylox) [C-II] COMMON USES: Moderate to severe pain 22 584 Clinician’s Pocket Reference, 9th Edition ACTIONS: Narcotic analgesic DOSAGE: Adults. 1–2 tabs/caps PO q4–6h PRN. Peds. Oxycodone 0.05–0.15 mg/kg/dose q4–6h PRN; up to 5 mg/dose SUPPLIED: Percocet tabs 5 mg of oxycodone, 325 mg of acetaminophen; Tylox caps 5 mg of oxy- codone, 500 mg of acetaminophen. Soln 5 mg of oxycodone and 325 mg of acetaminophen/5 mL NOTES: Acetaminophen max dose of 4 g/d Oxycodone and Aspirin (Percodan, Percodan-Demi) [C-II] COMMON USES: Moderate to moderately severe pain ACTIONS: Narcotic analgesic with NSAID DOSAGE: Adults.1–2 tabs/caps PO q4–6h PRN. Peds. 0.05–0.15 mg/kg/dose q4–6h, max 5 mg/dose (based on oxycodone) SUPPLIED: Percodan 4.5 mg oxycodone hydrochloride 0.38 mg oxycodone terephthalate, 325 mg aspirin; Percodan-Demi 2.25 mg oxycodone hydrochloride, 0.19 mg oxycodone terephthalate, 325 mg aspirin Oxymorphone (Numorphan) [C-II] COMMON USES: Moderate to severe pain, sedative ACTIONS: Narcotic analgesic DOSAGE: 0.5 mg IM, SC, IV initially, 1–1.5 mg q4–6h PRN. PR: 5 mg q4–6h PRN SUPPLIED: Inj 1, 1.5 mg/mL; supp 5 mg NOTES: Chemically related to hydromorphone Oxytocin (Pitocin, Syntocinon) COMMON USES: Induction of labor and control of postpartum hemorrhage; promote milk let down in lactating woman ACTIONS: Stimulate muscular contractions of the uterus, stimulate milk flow during nursing DOSAGE: 0.001–0.002 U/min IV inf; titrate to desired effect, to a max of 0.02 U/min. Breast feed- ing: 1 spray in both nostrils 2–3 min before feeding SUPPLIED: Inj 10 U/mL; nasal soln 40 U/mL NOTES: Can cause uterine rupture and fetal death; monitor vital signs closely; nasal form for breast feeding only Paclitaxel (Taxol) COMMON USES: Ovarian and breast cancer ACTIONS: Mitotic spindle poison promotes microtubule assembly and stabilization against depoly- merization (a taxrane) DOSAGE: 135–250 mg/m2 as a 3–24-h IV inf SUPPLIED: Inj 6 mg/mL NOTES: Toxicity symptoms: Hypersensitivity reactions (dyspnea, hypotension, urticaria, rash) usu- ally within 10 min of starting infusion; minimize with corticosteroid, antihistamine (H1 and H2 an- tagonist) pretreatment. Myelosuppression, peripheral neuropathy, transient ileus, myalgia, bradycardia, hypotension, mucositis, diarrhea, nausea and vomiting, fever, rash, headache, and phlebitis. Hematologic toxicity schedule-dependent; leukopenia dose-limiting by 24-h inf; neuro- toxicity dose-limiting by short (1–3-h) inf. Infuse this agent in glass or polyolefin containers using polyethylene-lined nitroglycerin tubing sets. PVC inf sets result in leaching of plasticizer Pamidronate (Aredia) COMMON USES: Hypercalcemia of malignancy and Paget’s disease; palliation of symptomatic bone metastases ACTIONS: Inhibition of normal and abnormal bone resorption DOSAGE: Hypercalcemia: 60 mg IV over 4 h or 90 mg IV over 24 h. Paget’s disease: 30 mg/d IV for 3 d 22 SUPPLIED: Powder for inj 30, 60, 90 mg 22 Commonly Used Medications 585 NOTES: Toxicity symptoms: Fever, tissue irritation at inj site, uveitis, fluid overload, HTN, abdomi- nal pain, nausea and vomiting, constipation, UTI, bone pain, hypokalemia, hypocalcemia, hypo- magnesemia, and hypophosphatemia; slow inf rate necessary Pancreatin/Pancrelipase (Pancrease, Cotazyme, Creon, Ultrase) COMMON USES: Exocrine pancreatic secretion deficiency (CF, chronic pancreatitis, other pancre- atic insufficiency) and for steatorrhea of malabsorption syndrome ACTIONS: Pancreatic enzyme supplementation DOSAGE: Adults & Peds. 1–3 caps (tabs) with meals and snacks; dosage ↑ to 8 caps (tabs) SUPPLIED: Caps, tabs NOTES: Avoid antacids; may cause nausea, abdominal cramps, or diarrhea; do not crush or chew EC products; dosage dependent on patient’s digestive requirements Pancuronium (Pavulon) COMMON USES: Rx of patients on mechanical ventilation ACTIONS: Nondepolarizing neuromuscular blocker DOSAGE: Adults. 2–4 mg IV q2–4h PRN. Peds. 0.02–0.10 mg/kg/dose q2–4h PRN SUPPLIED: Inj 1, 2 mg/mL NOTES: Intubate patient and keep on controlled ventilation; use an adequate amount of sedation or analgesia; adjust dose for renal or hepatic impairment Pantoprazole (Protonix) COMMON USES: GERD ACTION: Proton pump inhibitor DOSAGE: 40 mg/d PO SUPPLIED: Tabs 40 mg NOTES: DR tabs, therefore do NOT crush or chew tabs Paregoric [C] COMMON USES: Diarrhea, pain and neonatal opiate withdrawal syndrome ACTIONS: Narcotic DOSAGE: Adults. 5–10 mL PO qd–qid PRN. Peds. 0.25–0.5 mL/kg qd–qid. Neonatal withdrawal syndrome: 3–6 gtt PO q3–6h PRN to relieve symptoms for 3–5 d, then taper over 2–4 wk NOTES: Contains opium; short-term use only. (See also Kaolin-Pectin.) Paroxetine (Paxil) COMMON USES: Depression, OCD, panic disorder, and social anxiety disorder ACTIONS: Serotonin reuptake inhibitor DOSAGE: 10–60 mg PO as a single daily dose SUPPLIED: Tabs 10, 20, 30,40 mg; susp 10 mg/5 mL NOTES: Should be administered in AM; may cause sexual dysfunction Penbutolol (Levatol) COMMON USES: HTN ACTIONS: Competitively blocks β-adrenergic receptors, β1, β2 DOSAGE: 20–40 mg/d SUPPLIED: Tabs 20 mg Penciclovir (Denavir) COMMON USES: Herpes simplex ACTIONS: Competitive inhibitor of DNA polymerase DOSAGE: Apply topically at first sign of lesions, then q2h for 4 d SUPPLIED: Cream 1% 22 586 Clinician’s Pocket Reference, 9th Edition Penicillin G, Aqueous (Potassium or Sodium) (Pfizerpen) COMMON USES: Most gram (+) infections (except penicillin-resistant staphylococci), including streptococci, N. meningitidis, syphilis, clostridia, and some coliforms ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults. 400,000–800,000 U PO qid; IV doses vary greatly depending on indications; range from 1.2–24 million U/d in ÷ doses q4h. Peds. Newborns <1 wk: 25,000–50,000 U/kg/dose IV q12h. Infants 1 wk < 1 mo: 25,000–50,000 U/kg/dose IV q8h. Children: 100,000–300,000 U/kg/24h IV ÷ q4h SUPPLIED: Powder for inj NOTES: Beware of hypersensitivity reactions. Dosage adjustment in renal impairment Penicillin G Benzathine (Bicillin) COMMON USES: Useful as a single-dose treatment regimen for streptococcal pharyngitis, rheumatic fever and glomerulonephritis prophylaxis, and syphilis ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults. 1.2–2.4 million U deep IM inj q 2–4 wk. Peds. 50,000 U/kg/dose to a max of 2.4 million U/dose deep IM inj q 2–4 wk SUPPLIED: Inj 300,000, 600,000 U/mL NOTES: Sustained action with detectable levels up to 4 wk; considered the drug of choice for treat- ment of noncongenital syphilis; Bicillin L-A contains the benzathine salt only; Bicillin C-R con- tains a combination of the benzathine and procaine (300,000 U of procaine with 300,000 U of benzathine/mL or 900,000 U of benzathine with 300,000 U of procaine/2 mL) Penicillin G Procaine (Wycillin, others) COMMON USES: Moderately severe infections caused by penicillin G-sensitive organisms that re- spond to low, persistent serum levels ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults.0.6–4.8 million U/d in ÷ doses q12–24h. Peds. 25,000–50,000 U/kg/d IM ÷ qd–bid SUPPLIED: Inj 300,000, 500,000, 600,000 U/mL NOTES: Long-acting parenteral penicillin; blood levels up to 15 h; give probenecid at least 30 min prior to administration of penicillin to prolong action Penicillin V (Pen-Vee K, Veetids, others) COMMON USES: Most gram (+) infections, including streptococci, N. meningitidis, syphilis, clostridia, and some

coliforms ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults. 250–500 mg PO q6h. Peds. 25–50 mg/kg/24h PO in 4 ÷ doses SUPPLIED: Tabs 125, 250, 500 mg; susp 125, 250 mg/5 mL NOTES: Well-tolerated oral penicillin; 250 mg = 400,000 U of penicillin G Pentamidine (Pentam 300, Nebupent) COMMON USES: Rx and prevention of PCP ACTIONS: Inhibits DNA, RNA, phospholipid, and protein synthesis DOSAGE: Adults & Peds. 4 mg/kg/24h IV qd for 14–21 d. Adults & Peds >5 y. Prevention: 300 mg once q 4 wk, administered via Respigard II neb SUPPLIED: Inj 300 mg/vial; aerosol 300 mg NOTES: Monitor for severe hypotension following IV administration; associated with pancreatic islet cell necrosis leading to hypoglycemia and hyperglycemia; monitor hematology lab results for leukopenia and thrombocytopenia; IV requires dosage adjustment in renal impairment Pentazocine (Talwin) [C-IV] COMMON USES: Moderate to severe pain 22 22 Commonly Used Medications 587 ACTIONS: Partial narcotic agonist–antagonist DOSAGE: Adults. 30 mg IM or IV; 50–100 mg PO q3–4h PRN. Peds. 5–8 y: 15 mg IM q4h PRN. 8–14 y: 30 mg IM q4h PRN SUPPLIED: Tabs 50 mg (+ naloxone 0.5 mg); inj 30 mg/mL NOTES: 30–60 mg IM equianalgesic to 10 mg of morphine IM; associated with considerable dys- phoria; dosage adjustment in renal impairment Pentobarbital (Nembutal, others) [C-II] COMMON USES: Insomnia, convulsions, and induced coma following severe head injury ACTIONS: Barbiturate DOSAGE: Adults. Sedative: 20–40 mg PO or PR q6–12h. Hypnotic: 100–200 mg PO or PR hs PRN. Induced coma: Load 5–10 mg/kg IV, then maintenance 1–3 mg/kg/h IV cont inf to keep the serum level between 20 and 50 mg/mL. Peds. Hypnotic: 2–6 mg/kg/dose PO hs PRN. Induced coma: See adult dosage SUPPLIED: Caps 50, 100 mg; elixir 18.5 mg/5 mL; supp 30, 60, 120, 200 mg; inj 50 mg/mL NOTES: Can cause respiratory depression; may produce profound hypotension when used aggres- sively IV for cerebral edema; tolerance to sedative–hypnotic effect acquired within 1–2 wk; reduce dose in severe hepatic impairment Pentosan Polysulfate Sodium (Elmiron) COMMON USES: Relief of pain/discomfort associated with interstitial cystitis ACTIONS: Acts as buffer on bladder wall DOSAGE: 100 mg PO tid on empty stomach with water 1 h ac or 2 h pc SUPPLIED: Caps 100 mg NOTES: Toxicity symptoms: Alopecia, diarrhea, nausea, and headaches Pentostatin (Nipent) COMMON USES: Hairy cell leukemia, CLL, mycosis fungoides, ALL, and adult T-cell leukemia ACTIONS: Irreversible inhibitor of adenosine deaminase DOSAGE: 4–5 mg/m2/wk for 3 consecutive weeks SUPPLIED: Inj 10 mg NOTES: Toxicity symptoms: Renal dysfunction; myelosuppression (especially leukopenia), lympho- cytopenia, fever, and infection possible; neurologic toxicity symptoms (lethargy and fatigue, dry skin, keratoconjunctivitis, and nausea and vomiting); dosage adjustment in renal impairment Pentoxifylline (Trental) COMMON USES: Symptomatic management of peripheral vascular disease ACTIONS: Lowers blood cell viscosity by restoring erythrocyte flexibility DOSAGE: 400 mg PO tid pc SUPPLIED: Tabs 400 mg NOTES: Treat for at least 8 wk to see full effect; ↓ to bid if GI or CNS effects occur Pergolide (Permax) COMMON USES: Parkinson’s disease ACTIONS: Centrally active dopamine receptor agonist DOSAGE: Initially, 0.05 mg PO tid, titrated q 2–3 d to desired effect, usual maintenance dose 2–3 mg/d in ÷ doses SUPPLIED: Tabs 0.05, 0.25, 1.0 mg NOTES: May cause hypotension during initiation of therapy Perindopril Erbumine (Aceon) COMMON USES: HTN and CHF ACTIONS: ACE inhibitor DOSAGE: 4–8 mg/d 22 588 Clinician’s Pocket Reference, 9th Edition SUPPLIED: Tabs 2, 4, 8 mg NOTES: Avoid taking with food; dosage adjustment in renal impairment; contra in PRG Permethrin (Nix, Elimite) COMMON USES: Eradication of lice and scabies ACTIONS: Pediculicide DOSAGE: Adults & Peds. Saturate the hair and scalp; allow to remain in the hair for 10 min before rinsing out SUPPLIED: Topical liq 1%; cream 5% Perphenazine (Trilafon) COMMON USES: Psychotic disorders, intractable hiccups, and severe nausea ACTIONS: Phenothiazine; blocks postsynaptic mesolimbic dopaminergic receptors in the brain DOSAGE: Adults. Antipsychotic: 4–16 mg PO tid; max 64 mg/d. Hiccups: 5 mg IM q6h PRN or 1 mg IV at not less than 1–2 mg/min intervals to a max of 5 mg. Peds. 1–6 y: 4–6 mg/d in ÷ doses. 6–12 y: 6 mg/d in ÷ doses. >12 y: 4–16 mg 2–4×/d SUPPLIED: Tabs 2, 4, 8, 16 mg; oral conc 16 mg/5 mL; inj 5 mg/mL Phenazopyridine (Pyridium, others) COMMON USES: Lower urinary tract irritation ACTIONS: Local anesthetic on urinary tract mucosa DOSAGE: Adults. 100–200 mg PO tid. Peds 6–12 y. 12 mg/kg/24h PO in 3 ÷ doses SUPPLIED: Tabs 95, 100, 200 mg NOTES: GI disturbances; causes red-orange urine color, which can stain clothing; dosage adjust- ment in renal impairment Phenelzine (Nardil) COMMON USES: Depression ACTIONS: MAO inhibitor DOSAGE: Adults. 15 mg tid. Elderly: 15–60 mg/d in ÷ doses SUPPLIED: Tabs 15 mg NOTES: May cause postural hypotension; may take 2–4 wk to see therapeutic effect; avoid tyra- mine-containing foods Phenobarbital [C-IV] COMMON USES: Seizure disorders, insomnia, and anxiety ACTIONS: Barbiturate DOSAGE: Adults. Sedative–hypnotic: 30–120 mg/f PO or IM PRN. Anticonvulsant: Loading dose of 10–12 mg/kg in 3 ÷ doses, then 1–3 mg/kg/24h PO, IM, or IV. Peds. Sedative–hypnotic: 2–3 mg/kg/24h PO or IM hs PRN. Anticonvulsant: Loading dose of 15–20 mg/kg ÷ into 2 equal doses 4 h apart, then 3–5 mg/kg/24h PO ÷ in 2–3 doses SUPPLIED: Tabs 8, 15, 16, 30, 32, 60, 65, 100 mg; elixir 15, 20 mg/5 mL; inj 30, 60, 65, 130 mg/mL NOTES: Tolerance develops to sedation; paradoxic hyperactivity seen in pediatric patients; long half-life allows single daily dosing. (See Table 22–7, pages 631–634.) Phenylephrine (Neo-Synephrine) COMMON USES: Vascular failure in shock, hypersensitivity, or drug-induced hypotension; nasal congestion; mydriatic ACTIONS: α-Adrenergic agonist DOSAGE: Adults. Mild to moderate hypotension: 2–5 mg IM or SC elevates BP for 2 h; 0.1–0.5 mg IV elevates BP for 15 min. Severe hypotension or shock: Initiate cont inf at 100–180 mg/min; after BP is stabilized, maintenance rate of 40–60 mg/min. Nasal congestion: 1–2 sprays/nostril PRN. 22 Ophth: 1 gtt 15–30 min before examination. Peds. Hypotension: 5–20 µg/kg/dose IV q 10–15 min 22 Commonly Used Medications 589 or 0.1–0.5 mg/kg/min IV infusion, titrated to desired effect. Nasal congestion: 1 spray/nostril q3–4h PRN SUPPLIED: Inj 10 mg/mL; nasal soln 0.125, 0.16, 0.25, 0.5, 1%; ophth soln 0.12, 2.5, 10% NOTES: Promptly restore blood volume if loss has occurred; use with extreme caution in patients with hyperthyroidism, bradycardia, partial heart block, myocardial disease, or severe arteriosclero- sis; use large veins for infusion to avoid extravasation; phentolamine 10 mg in 10–15 mL of NS for local inj as antidote for extravasation; activity potentiated by oxytocin, MAO inhibitors, and tri- cyclic antidepressants. (See Table 20–10, page 637.) Phenytoin (Dilantin) COMMON USES: Seizure disorders ACTIONS: Inhibits seizure spread in the motor cortex DOSAGE: Adults & Peds. Load: 15–20 mg/kg IV at a max inf rate of 25 mg/min or orally in 400- mg doses at 4-h intervals. Adults. Maintenance: Initially, 200 mg PO or IV bid or 300 mg hs; then follow serum concentrations. Peds. Maintenance: 4–7 mg/kg/24h PO or IV ÷ qd–bid SUPPLIED: Caps 30, 100 mg; chewable tabs 50 mg; oral susp 30, 125 mg/5 mL; inj 50 mg/mL NOTES: Use caution with cardiac depressant side effects, especially with IV administration; follow levels as needed (see Table 22–7, pages 631–634); nystagmus and ataxia early signs of toxicity; gum hyperplasia occurs with long-term use; avoid use of oral susp if possible because of erratic ab- sorption; avoid use in pregnancy Physostigmine (Antilirium) COMMON USES: Antidote for tricyclic antidepressant, atropine, and scopolamine overdose; glau- coma ACTIONS: Reversible cholinesterase inhibitor DOSAGE: Adults. 2 mg IV or IM q 20 min. Peds. 0.01–0.03 mg/kg/dose IV q 15–30 min, to total of 2 mg if necessary SUPPLIED: Inj 1 mg/mL; ophth oint 0.25% NOTES: Rapid IV administration associated with convulsions; cholinergic side effects; may cause asystole. (See also Chapter 21.) Phytonadione [Vitamin K] (AquaMEPHYTON, others) COMMON USES: Coagulation disorders caused by faulty formation of factors II, VII, IX, and X; hy- peralimentation ACTIONS: Supplementation; needed for the production of factors II, VII, IX, and X DOSAGE: Children and Adults. Anticoagulant-induced prothrombin deficiency: 2.5–10.0 mg PO or IV slowly. Hyperalimentation: 10 mg IM or IV q wk. Infants. 0.5–1.0 mg/dose IM, SC, or PO SUPPLIED: Tabs 5 mg; inj 2, 10 mg/mL NOTES: With parenteral treatment, the first change in prothrombin usually seen in 12–24 h; ana- phylaxis can result from IV dosage; administer IV slowly Pindolol (Visken) COMMON USES: HTN ACTIONS: Competitively blocks β-adrenergic receptors, β1, β2, ISA DOSAGE: 5–10 mg bid, to max dose of 60 mg/d SUPPLIED: Tabs 5, 10 mg Pioglitazone (Actos) COMMON USES: Type 2 DM in combination with diet or other agents ACTIONS: Increases insulin sensitivity DOSAGE: 15–45 mg/d SUPPLIED: Tabs 15, 30, 45 mg NOTES: Do NOT use in hepatic impairment 22 590 Clinician’s Pocket Reference, 9th Edition Pipecuronium (Arduan) COMMON USES: Adjunct to general anesthesia ACTIONS: Nondepolarizing neuromuscular blocker DOSAGE: Adults & Peds. 0.05–0.085 mg/kg initially, followed by 0.5–2 µg/kg/min (ICU) SUPPLIED: Inj 10 mg NOTES: Dosage adjustment in renal failure Piperacillin (Pipracil) COMMON USES: Infections caused by susceptible strains of gram– bacteria (including Klebsiella, Proteus, E. coli, Enterobacter, P. aeruginosa, and Serratia) involving the skin, bone, respiratory tract, urinary tract, abdomen, and septicemia ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults. 3 gm IV q4–6h. Peds. 200–300 mg/kg/d IV ÷ q4–6h SUPPLIED: Inj NOTES: Often used in combination with aminoglycosides; dosage adjustment in renal failure Piperacillin-Tazobactam (Zosyn) COMMON USES: Infections caused by susceptible strains of gram (−) bacteria (including Kleb- siella, Proteus, E. coli, Enterobacter, P. aeruginosa, and Serratia) involving the skin, bone, respira- tory tract, urinary tract, abdomen, and septicemia ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults. 3.375–4.5 g IV q6h SUPPLIED: Inj NOTES: Often used in combination with aminoglycoside; dosage adjustment in renal failure Pirbuterol (Maxair) COMMON USES: Prevention and Rx of reversible bronchospasm ACTIONS: β2-Adrenergic agonist DOSAGE: Adults & Peds >12 y. 2 inhal q4–6h; max 12 inhal/d SUPPLIED: Aerosol 0.2 mg/actuation NOTES: Mouth rinsed with water after each use Piroxicam (Feldene) COMMON USES: Arthritis and pain ACTIONS: NSAID; inhibits prostaglandin synthesis DOSAGE: 10–20 mg/d SUPPLIED: Caps 10, 20 mg Plasma Protein Fraction (Plasmanate, others) COMMON USES: Shock and hypotension ACTIONS: Plasma volume expansion DOSAGE: Adults. Initially, 250–500 mL IV (NOT >10 mL/min); subsequent inf depend on clinical response. Peds. 10–15 mL/kg/dose IV; subsequent inf depend on clinical response SUPPLIED: Inj 5% NOTES: Hypotension associated with rapid inf; 130–160 meq Na/L; NOT substitute for RBC Plicamycin (Mithracin) COMMON USES: Hypercalcemia of malignancy; disseminated embryonal cell carcinoma or germ cell tumors of the testis ACTIONS: Antibiotic; binds to the outside of the DNA molecule, interrupting DNA-directed RNA synthesis, DNA intercalation DOSAGE: Hypercalcemia: 25 mg/kg/d IV qod for 3–8 doses. Cancer: 25–30 mg/kg/d for 8–10 d 22 SUPPLIED: Inj 22 Commonly Used Medications 591 NOTES: Toxicity symptoms: Thrombocytopenia; drug-induced deficiency of clotting factors II, V, VII, and X, resulting in bleeding and bruising; dosage adjustment in renal or hepatic impairment Pneumococcal Vaccine, Polyvalent (Pneumovax-23) COMMON USES: Immunization against pneumococcal infections in patients predisposed to or at high risk. (See Table 22–9, page 636.) ACTIONS: Active immunization DOSAGE: Adults & Peds >2 y. 0.5 mL IM SUPPLIED: Inj 25 mg each of polysaccharide isolates/0.5-mL dose NOTES: Do NOT vaccinate during immunosuppressive therapy Pneumococcal 7-valent Conjugate Vaccine (Prevnar) COMMON USES: Immunization against pneumococcal infections in infants and children. (See Table 22–9, page 636.) ACTIONS: Active immunization DOSAGE: 0.5 mL IM/dose; series consists of 3 doses; 1st dose at 2 mo of age with subsequent doses q 2 mo SUPPLIED: Inj Podophyllin (Podocon-25, Condylox Gel 0.5%, Condylox) COMMON USES: Topical therapy of benign growths (genital and perianal warts [condylomata acuminata], papillomas, fibroids ACTIONS: Direct antimitotic effect. Exact mechanism unknown DOSAGE: Condylox gel and Condylox are applied 3 consecutive d/wk for 4 wk. Use Podocon-25 sparingly on the lesion, leave on for 1–4 h, then thoroughly wash off SUPPLIED: Podocon-25 contains benzoin 15 mL bottles; Condylox gel 0.5% 35 g clear gel; Condy- lox soln 0.5% 35 g clear NOTES: Podocon-25 applied only by the clinician; NOT to be dispensed to patient. Contra in PRG, diabetics, bleeding lesions, immunocompromised Polyethylene Glycol [PEG] Electrolyte Solution (GoLYTELY, CoLyte) COMMON USES: Bowel cleansing prior to examination or surgery ACTIONS: Osmotic cathartic DOSAGE: Adults. Following 3–4-h fast, drink 240 mL of soln q 10 min until 4 L is consumed. Peds. 25–40

mL/kg/h for 4–10 h SUPPLIED: Powder for reconstitution to 4 L in container NOTES: 1st bowel movement should occur in approximately 1 h; may cause some cramping or nausea Polymyxin B and Hydrocortisone (Otobiotic Otic) COMMON USES Superficial bacterial infections of external ear canal ACTIONS: Antibiotic antiinflammatory combination DOSAGE: 4 gtt in ear(s) tid–qid SUPPLIED: Soln polymyxin B 10,000 U/ hydrocortisone 0.5%/ mL NOTES: Useful in neomycin allergy Potassium Citrate (Urocit-K) COMMON USES: Alkalinize urine, prevention of urinary stones (uric acid, calcium stones if hypoci- traturic) ACTIONS: Urinary alkalinizer DOSAGE: 10–20 mEq PO tid with meals, max 100 mEq/d NOTES: Tabs 540 mg = 5 mEq, 1080 mg = 10 mEq 22 592 Clinician’s Pocket Reference, 9th Edition Potassium Citrate and Citric Acid (Polycitra-K) COMMON USES: Alkalinize urine, prevention of urinary stones (uric acid, calcium stones if hypoci- traturic) ACTIONS: Urinary alkalinizer DOSAGE: 10–20 mEq PO tid with meals, max 100 mEq/d NOTES: Soln 10 mEq/5 mL; powder 30 mEq/packet Potassium Idodide [Lugol’s Solution] (SSKI, Thyro-Block) COMMON USES: Thyroid crisis, reduction of vascularity before thyroid surgery, block thyroid up- take of radioactive isotopes of iodine, thin bronchial secretions ACTIONS: Iodine supplement DOSAGE: Adults & Peds. Preop thyroidectomy: 50–250 mg PO tid (2–6 gtt strong iodine soln); ad- minister 10 d preop. Thyroid crisis: Adults & Peds >1 y. 300 mg (6 gtt SSKI q8h). Infants <1 y. ¹₂ dose) SUPPLIED: Tabs 130 mg; soln SSKI 1 g/mL; Lugol’s soln, strong iodine 100 mg/mL ; syrup 325 mg/5 mL Potassium Supplements (Kaon, Kaochlor, K-Lor, Slow-K, Micro-K, Klorvess, others). (See Table 22–4, page 626.) COMMON USES: Prevention or Rx of hypokalemia (often related to diuretic use) ACTIONS: Supplementation of potassium DOSAGE: Adult: 20–100 mEq/d PO ÷ qd–bid; IV 10–20 mEq/h, max 40 mEq/h and 150 mEq/d (monitor frequent potassium levels when using high-dose IV infusions). Peds. Calculate potassium deficit; 1–3 mEq/kg/d PO ÷ qd–qid; IV max dose 0.5–1 mEq/kg/h SUPPLIED: Oral forms (see Table 22–4, page 626); injectable forms NOTES: Can cause GI irritation; mix powder and liquid with beverage (unsalted tomato juice, etc); use cautiously in renal insufficiency as well as with NSAIDs and ACE inhibitors. Cl salt recom- mended in coexisting alkalosis, for coexisting acidosis use acetate, bicarbonate, citrate or gluconate salt. (See also Chapter 9.) Pramipexole (Mirapex) COMMON USES: Parkinson’s disease ACTION: Dopamine agonist DOSAGE: 1.5–4.5 mg/d, beginning with 0.375 mg/d in 3 ÷ doses SUPPLIED: Tabs 0.125, 0.25, 1, 1.5 mg NOTES: Titrate dosage slowly Pramoxine (Anusol Ointment, Proctofoam-NS, others) COMMON USES: Relief of pain and itching from external and internal hemorrhoids and anorectal surgery; topical for burns and dermatosis ACTIONS: Topical anesthetic DOSAGE: Apply cream, oint, gel or spray, freely to anal area q3–h SUPPLIED: [OTC] all 1%; foam (Proctofoam NS), cream, oint, lotion, gel, pads, spray Pramoxine + Hydrocortisone (Enzone, Proctofoam-HC) COMMON USES: Relief of pain and itching from hemorrhoids ACTIONS: Topical anesthetic DOSAGE: Apply freely to anal area tid–qid SUPPLIED: Cream pramoxine hydrochloride 1% hydrocortisone acetate 0.5/1%; foam pramoxine 1% hydrocortisone 1%; lotion pramoxine 1% hydrocortisone 0.25/1/2.5%, pramoxine 2.5% and hydrocortisone 1% Pravastatin (Pravachol) COMMON USES: Reduction of elevated cholesterol levels 22 ACTIONS: HMG-CoA reductase inhibitor 22 Commonly Used Medications 593 DOSAGE: 10–40 mg PO hs SUPPLIED: Tabs 10, 20, 40 mg NOTES: Avoid concurrent use with gemfibrozil. Follow LFT’s Prazepam (Centrax) [C] COMMON USES: Anxiety disorders and alcohol withdrawal ACTIONS: Benzodiazepine DOSAGE: 5–10 mg PO tid–qid, or 20–50 mg PO as a single dose hs to minimize daytime drowsi- ness SUPPLIED: Discontinued Prazosin (Minipress) COMMON USES: HTN and CHF ACTIONS: Peripherally acting α-adrenergic blocker DOSAGE: Adults. 1 mg PO tid; can ↑ to max daily dose of up to 20 mg/d. Peds. 5–25 µg/kg/dose q6h, up to 25 µg/kg/dose SUPPLIED: Caps 1, 2, 5 mg NOTES: Can cause orthostatic hypotension, so the patient should take the first dose hs; tolerance de- velops to this effect; tachyphylaxis may result Prednisolone See Steroids, systemic (Table 22–5, page 627) Prednisone See Steroids, systemic (Table 22–5, page 627) Probenecid (Benemid, others) COMMON USES: Prevention of gout and hyperuricemia; prolong serum levels of penicillins or cephalosporins ACTIONS: Renal tubular blocking agent DOSAGE: Adults. Gout: 250 mg bid for 1 wk, then 0.5 g PO bid. Can ↑ by 500 mg/mo up to 2–3 g/d. Antibiotic effect: 1–2 g PO 30 min prior to dose of antibiotic. Peds >2 y. 25 mg/kg, then 40 mg/kg/d PO ÷ qid SUPPLIED: Tabs 500 mg Procainamide (Pronestyl, Procan) Used for emergency cardiac care (see Chapter 21) COMMON USES: Supraventricular and ventricular arrhythmias ACTIONS: Class 1A antiarrhythmic DOSAGE: Adults. For emergency cardiac care, see Chapter 21. Chronic dosing: 50 mg/kg/d PO in ÷ doses q4–6h. Peds. For emergency cardiac care, see Chapter 21. Maintenance: 15–50 mg/kg/24h PO ÷ q3–6h SUPPLIED: Tabs and caps 250, 375, 500 mg; SR tabs 250, 500, 750, 1000 mg; inj 100, 500 mg/mL NOTES: Can cause hypotension and a lupus-like syndrome; dosage adjustment required with renal or hepatic impairment (see Table 22–7, pages 631–634. See also Table 20–10, p. 637.) Procarbazine (Matulane) COMMON USES: Hodgkin’s disease, non-Hodgkin’s lymphoma, and brain tumors ACTIONS: Alkylating agent; inhibition of DNA and RNA synthesis DOSAGE: 2–4 mg/kg/d × 7 d, then 4–6 mg/kg/d until response. Maintenance 1–2 mg/kg/d/ in com- bination, 60–100 mg/m2/d × 10–14 d SUPPLIED: Caps 50 mg NOTES: Toxicity symptoms: Myelosuppression, hemolytic reactions (with G6PD deficiency), nau- sea, vomiting, and diarrhea; disulfiram-like reaction. Cutaneous reactions. Constitutional symp- 22 594 Clinician’s Pocket Reference, 9th Edition toms, myalgia, and arthralgia. CNS effects may be related to the high concentrations of drug reached in CSF or because of MAO inhibitor effects. Azoospermia and cessation of menses com- mon Prochlorperazine (Compazine) COMMON USES: Nausea and vomiting, agitation, and psychotic disorders ACTIONS: Phenothiazine; blocks postsynaptic mesolimbic dopaminergic receptors in the brain DOSAGE: Adults. Antiemetic: 5–10 mg PO tid–qid or 25 mg PR bid or 5–10 mg deep IM q4–6h. Antipsychotic: 10–20 mg IM acutely or 5–10 mg PO tid–qid for maintenance. Peds. 0.1–0.15 mg/kg/dose IM q4–6h or 0.4 mg/kg/24h PO ÷ tid–qid SUPPLIED: Tabs 5, 10, 25 mg; SR caps 10, 15, 30 mg; syrup 5 mg/5 mL; supp 2.5, 5, 25 mg; inj 5 mg/mL NOTES: A much larger dose may be required for antipsychotic effect; extrapyramidal side effects common; treat acute extrapyramidal reactions with diphenhydramine Procyclidine (Kemadrin) COMMON USES: Parkinson’s syndrome ACTIONS: Blocking excess acetylcholine DOSAGE: 2.5 mg PO tid, up to 20 mg/d SUPPLIED: Tabs 5 mg NOTES: Contra in glaucoma Promethazine (Phenergan) COMMON USES: Nausea and vomiting, motion sickness, sedation ACTIONS: Phenothiazine; blocks postsynaptic mesolimbic dopaminergic receptors in the brain DOSAGE: Adults. 12.5–50 mg PO, PR, or IM bid–qid PRN. Peds. 0.1–0.5 mg/kg/dose PO or IM q12–6h PRN SUPPLIED: Tabs 12.5, 25, 50 mg; syrup 6.25 mg/5 mL, 25 mg/5 mL; supp 12.5, 25, 50 mg; inj 25, 50 mg/mL NOTES: High incidence of drowsiness Propafenone (Rythmol) COMMON USES: Life-threatening ventricular arrhythmias ACTIONS: Class IC antiarrhythmic DOSAGE: 150–300 mg PO q8h SUPPLIED: Tabs 150, 225, 300 mg NOTES: May cause dizziness, unusual taste, 1st-degree heart block, and prolongation of QRS and QT intervals Propantheline (Pro-Banthine) COMMON USES: Symptomatic treatment of small intestine hypermotility, spastic colon, ureteral spasm, bladder spasm, pylorospasm ACTIONS: Antimuscarinic agent DOSAGE: Adults. 15 mg PO ac and 30 mg PO hs. Peds. 1–3 mg/kg/24h PO ÷ tid–qid SUPPLIED: Tabs 7.5, 15 mg NOTES: Anticholinergic side effects, eg, dry mouth and blurred vision common Propofol (Diprivan) COMMON USES: Induction or maintenance of anesthesia; continuous sedation in intubated patients ACTIONS: Sedative hypnotic; mechanism unknown DOSAGE: Anesthesia: 2–2.5 mg/kg induction then 0.1–0.2 mg/kg/min cont inf. ICU sedation: 5–50 µg/kg/min cont inf SUPPLIED: Inj 10 mg/mL NOTES: 1 mL of propofol contains 0.1 g of fat; may increase serum triglycerides when adminis- 22 tered for extended periods 22 Commonly Used Medications 595 Propoxyphene (Darvon) [C-IV] Propoxyphene and Acetaminophen (Darvocet) [C-IV] Propoxyphene and Aspirin (Darvon Compound-65, Darvon-N + Aspirin) [C-IV] COMMON USES: Mild to moderate pain ACTIONS: Narcotic analgesic DOSAGE: 1–2 PO q4h PRN SUPPLIED: Darvon: propoxyphene HCl caps 65 mg; Darvon-N: propoxyphene napsylate 100-mg tabs; Darvocet-N: propoxyphene napsylate 50 mg/acetaminophen 325 mg; Darvocet-N 100: propoxyphene napsylate 100 mg/acetaminophen 650 mg; Darvon Compound-65: propoxyphene HCl 65-mg/aspirin 389-mg/caffeine 32-mg caps; Darvon-N with aspirin: propoxyphene napsylate 100 mg/aspirin 325 mg NOTES: Intentional overdose can be lethal Propranolol (Inderal) Used for emergency cardiac care (see also Chapter 21) COMMON USES: HTN, angina, MI ACTIONS: Competitively blocks β-adrenergic receptors, β1, β2 DOSAGE: Adults. Angina: 80–320 mg/d PO ÷ bid–qid or 80–160 mg/d SR. Arrhythmia: 10–80 mg PO tid–qid or 1 mg IV slowly, repeat q 5 min up to 5 mg. HTN: 40 mg PO bid or 60–80 mg/d SR, ↑ weekly to max 640 mg/d. Hypertrophic subaortic stenosis: 20–40 mg PO tid–qid. MI: 180–240 mg PO ÷ tid–qid. Migraine prophylaxis: 80 mg/d ÷ qid–tid, ↑ weekly to max 160–240 mg/d ÷ tid–qid; wean off if no response in 6 wk. Pheochromocytoma: 30–60 mg/d ÷ tid–qid. Thyrotoxicosis: 1–3 mg IV single dose; 10–40 mg PO q6h. Tremor: 40 mg PO bid, ↑ as needed to max 320 mg/d. Peds. Arrhythmia: 0.5–1.0 mg/kg/d ÷ tid–qid, ↑ as needed q3–7d to max 60 mg/d; 0.01–0.1 mg/kg IV over 10 min, max dose 1 mg. HTN: 0.5–1.0 mg/kg ÷ bid–qid, ↑ as needed q 3–7 d to 2 mg/kg/d max SUPPLIED: Tabs 10, 20, 40, 60, 80, 90 mg; caps SR 60, 80, 120, 160 mg; oral soln 4 mg/mL, 8 mg/mL, 80 mg/mL; inj 1 mg/mL NOTES: Dosage adjustment in renal impairment Propylthiouracil [PTU] COMMON USES: Hyperthyroidism ACTIONS: Inhibits production of T3 and T4 and conversion of T4 to T3 DOSAGE: Adults. Initial: 100 mg PO q8h (may need up to 1200 mg/d for control); after the patient is euthyroid (6–8 wk), taper the dose by 1⁄2 q 4–6 wk to Maintenance: 50–150 mg/24h; can usually be discontinued in 2–3 y. Peds. Initial: 5–7 mg/kg/24h PO ÷ q8h. Maintenance: 1⁄3–2⁄3 of the initial dose SUPPLIED: Tabs 50 mg NOTES: Follow the patient clinically; monitor TFT Protamine Sulfate COMMON USES: Reversal of heparin effect ACTIONS: Neutralizes heparin by forming a stable complex DOSAGE: Adults & Peds. Based on amount of heparin reversal desired; give IV slowly; 1 mg re- verses approximately 100 U of heparin given in the preceding 3–4 h, to a max dose of 50 mg SUPPLIED: Inj 10 mg/mL NOTES: Follow coagulation studies; may have anticoagulant effect if given without heparin Pseudoephedrine (Sudafed, Novafed, Afrinol, others) COMMON USES: Decongestant ACTIONS: Stimulates α-adrenergic receptors, resulting in vasoconstriction DOSAGE: Adults. 30–60 mg PO q6–8h; SR caps 120 mg PO q12h. Peds. 4 mg/kg/24h PO ÷ qid 22 596 Clinician’s Pocket Reference, 9th Edition SUPPLIED: Tabs 30, 60 mg; caps 60 mg; SR tabs 120, 240 mg; SR caps 120 mg; liq 7.5 mg/0.8 mL, 15, 30 mg/5 mL NOTES: Contra in patients with poorly controlled HTN or CAD and in patients taking MAO in- hibitors; ingredient in many cough and cold preparations Psyllium (Metamucil, Serutan, Effer-Syllium) COMMON USES: Constipation and diverticular disease of the colon ACTIONS: Bulk laxative DOSAGE: 1 tsp (7 g) in a glass of water qd–tid SUPPLIED: Granules 4, 25 g/tsp; powder 3.5 g/packet NOTES: Do NOT use if suspected bowel obstruction; one of the safest laxatives; psyllium in effer- vescent (Effer-Syllium) form usually contains potassium and should be used with caution in renal failure Pyrazinamide COMMON USES: Active TB ACTIONS: Bacteriostatic; mechanism unknown DOSAGE: Adults. 15–30 mg/kg/24h PO ÷ tid–qid; max 2 g/d. Peds. 15–30 mg/kg/d PO ÷ qd–bid SUPPLIED: Tabs 500 mg NOTES: May cause hepatotoxicity; use in combination with other antituberculosis drugs; consult MMWR for the latest recommendations on the treatment of tuberculosis; dosage regimen differs for directly observed therapy; adjust dose for renal or hepatic impairment Pyridoxine [Vitamin B6] (Nestrex) COMMON USES: Rx and prevention of vitamin B6 deficiency, including drug-induced (ie INH, hy- dralazine) ACTIONS: Supplementation of vitamin B6 DOSAGE: Adults. Deficiency: 10–20 mg/d. PO Drug-induced neuritis: 100–200 mg/d; 25–100 mg/d prophylaxis. Peds. 5–25 mg/d × 3 wk SUPPLIED: Tabs 25, 50, 100 mg; inj 100 mg/mL Quazepam (Doral) [CIV] COMMON USES: Insomnia ACTIONS: Benzodiazepine DOSAGE: 7.5–15 mg PO hs PRN SUPPLIED: Tabs 7.5, 15 mg NOTES: ↓ Dose in the elderly; do NOT discontinue abruptly Quetiapine (Seroquel) COMMON USES: Acute exacerbations of schizophrenia ACTIONS: Serotonin and dopamine antagonism DOSAGE: 150–750; mg/d; initiate at 25–100 mg bid–tid SUPPLIED: Tabs

25, 100, 200 mg NOTES: ↑ Dose slowly; adjust dose for hepatic and geriatric patients Quinapril (Accupril) COMMON USES: HTN and heart failure ACTIONS: ACE inhibitor DOSAGE: 10–80 mg PO qd in a single dose SUPPLIED: Tabs 5, 10, 20, 40 mg NOTES: Dosage adjustment in renal impairment Quinidine (Quinidex, Quinaglute) 22 COMMON USES: Prevention of tachydysrhythmias 22 Commonly Used Medications 597 ACTIONS: Class 1A antiarrhythmic DOSAGE: Adults. PAC, PVCs: 200–300 mg PO tid–qid. Conversion of AF or flutter: Use after digi- talization, 200 mg q2–3h for 8 doses; then ↑ daily dose to a max of 3–4 g or until normal rhythm. Peds. 15–60 mg/kg/24h PO in 4–5 ÷ dose SUPPLIED: Sulfate: Tabs 200, 300 mg; SR tabs 300 mg; Gluconate: SR tabs 324 mg; inj 80 mg/mL NOTES: Contra in digitalis toxicity and AV block; follow serum levels if available (see Table 22–7, pages 631–634); extreme hypotension seen with IV administration. Sulfate salt contains 83% quinidine; gluconate salt contains 62% quinidine; dosage adjustment in renal impairment Quinupristin/Dalfopristin (Synercid) COMMON USES: Infections caused by vancomycin-resistant Entercoccus faecium, and other gram+ organisms ACTIONS: Inhibits both the early and late phase of protein synthesis at the ribosomes DOSAGE: Adults & Peds. 7.5 mg/kg IV q8–12h SUPPLIED: Inj 500 mg (150 mg quinupristin/350 mg dalfopristin) NOTES: Administer through central line if possible; NOT compatible with saline or heparin, there- fore flush IV lines with dextrose Rabeprazole (Aciphex) COMMON USES: Peptic ulcers, GERD, and hypersecretory conditions ACTIONS: Proton pump inhibitor DOSAGE: 20 mg/d; may be ↑ to 60 mg/d SUPPLIED: Tabs 60 mg NOTES: Do NOT crush tabs Raloxifene (Evista) COMMON USES: Prevention of osteoporosis ACTIONS: Partial antagonist of estrogen that behaves like estrogen DOSAGE: 60 mg/d SUPPLIED: Tabs 60 mg Ramipril (Altace) COMMON USES: HTN and heart failure ACTIONS: ACE inhibitor DOSAGE: 2.5–20 mg/d PO ÷ qd–bid SUPPLIED: Caps 1.25, 2.5, 5, 10 mg NOTES: May use in combination with diuretics; may cause a nonproductive cough; dosage adjust- ment in renal impairment Ranitidine (Zantac) COMMON USES: Duodenal ulcer, active benign ulcers, hypersecretory conditions, and GERD ACTIONS: H2-receptor antagonist DOSAGE: Adults. Ulcer: 150 mg PO bid, 300 mg PO hs, or 50 mg IV q6–8h; or 400 mg IV/d cont inf, then maintenance of 150 mg PO hs. Hypersecretion: 150 mg PO bid, up to 600 mg/d. GERD: 300 mg PO bid; maintenance 300 mg PO hs. Peds. 0.75–1.5 mg/kg/dose IV q6–8h or 1.25–2.5 mg/kg/dose PO q12 SUPPLIED: Tabs 75, 150, 300 mg; syrup 15 mg/mL; inj 25 mg/mL NOTES: ↓ Dose with renal failure; oral and parenteral doses are different Repaglinide (Prandin) COMMON USES: Type 2 DM ACTIONS: Stimulates insulin release from pancreas DOSAGE: 0.5–4 mg ac SUPPLIED: Tabs 0.5, 1, 2 mg 22 598 Clinician’s Pocket Reference, 9th Edition Reteplase (Retavase) COMMON USES: Post-AMI ACTIONS: Thrombolytic agent DOSAGE: 10 U IV over 2 min, 2nd dose 30 min later of 10 U IV over 2 min SUPPLIED: Inj 10.8 U/2 mL Ribavirin (Virazole) COMMON USES: RSV infection in infants and; hepatitis C, (in combination with interferon alfa-2b) ACTIONS: Unknown DOSAGE: RSV: 6 g in 300 mL of sterile water inhaled over 12–18 h. Hep C: 600 mg PO bid in com- bination with interferon alfa-2b (See Rebetron, page 000) SUPPLIED: Powder for aerosol 6 g; caps 200 mg NOTES: Aerosolized by a SPAG ; may accumulate on soft contact lenses; monitor H/H frequently; PRG test monthly Rifabutin (Mycobutin) COMMON USES: Prevention of M. avium complex infection in AIDS patients with a CD4 count <100 ACTIONS: Inhibits DNA-dependent RNA polymerase activity DOSAGE: 150–300 mg/d PO SUPPLIED: Caps 150 mg NOTES: Adverse effects and drug interactions similar to rifampin Rifampin (Rifadin) COMMON USES: TB and Rx and prophylaxis of N. meningitidis, H. influenzae, or S. aureus carriers ACTIONS: Inhibits DNA-dependent RNA polymerase activity DOSAGE: Adults. N. meningitidis and H. influenzae carrier: 600 mg/d PO for 4 d. TB: 600 mg PO or IV qd or 2×/wk with combination-therapy regimen. Peds. 10–20 mg/kg/dose PO or IV qd–bid SUPPLIED: Caps 150, 300 mg; inj 600 mg NOTES: Multiple drug interactions; causes orange-red discoloration of bodily secretions, including tears; never used as a single agent to treat active TB Rifapentine (Priftin) COMMON USES: TB ACTIONS: Inhibits DNA-dependent RNA polymerase activity DOSAGE: Intensive phase: 600 mg PO 2×/wk for 2 mo; separate doses by 3 or more days. Continu- ation phase: 600 mg/wk SUPPLIED: Tabs 150 mg NOTES: Adverse effects and drug interactions similar to rifampin Rimantadine (Flumadine) COMMON USES: Prophylaxis and Rx of influenza A virus infections ACTIONS: Antiviral agent DOSAGE: Adults. 100 mg PO bid. Peds. 5 mg/kg/d PO, NOT to exceed 150 mg/d SUPPLIED: Tabs 100 mg; syrup 50 mg/5 mL NOTES: Dosage adjustment in severe renal or hepatic impairment; initiate within 48 h of symptom onset Rimexolone (Vexol Ophthalmic) COMMON USES: Postop inflammation and uveitis ACTIONS: Steroid DOSAGE: Adults & Peds > 2 y. Uveitis: 1–2 gtt/h daytime and q2h at night, taper to 1 gtt q4h; postop 1–2 gtt qid up to 2 wk 22 22 Commonly Used Medications 599 SUPPLIED: 1% susp NOTES: Taper dose to zero Risedronate (Actonel) COMMON USES: Prevention and Rx of postmenopausal osteoporosis; Paget’s disease ACTIONS: Bisphosphonate; inhibits osteoclast-mediated bone resorption DOSAGE: 5 mg/d PO with 6–8 oz water; 30 mg/d for 2 mo for Paget’s disease SUPPLIED: Tabs 5, 30 mg NOTES: Take 30 min before first food or drink of the day; maintain upright position for at least 30 min after administration, interaction with calcium supplements; may cause GI distress and arthral- gia; NOT recommended in moderate to severe renal impairment Risperidone (Risperdal) COMMON USES: Psychotic disorders ACTIONS: Benzisoxazole antipsychotic agent DOSAGE: 1–6 mg PO bid SUPPLIED: Tabs 1, 2, 3, 4 mg NOTES: ↓ Starting doses in elderly, renal or hepatic impairment; orthostatic hypotension; extrapyra- midal reactions with higher doses Ritonavir (Norvir) COMMON USES: HIV infection when therapy is warranted ACTIONS: Protease inhibitor; inhibits maturation of immature noninfectious virions to mature in- fectious virus DOSAGE: 600 mg PO bid or 400 mg PO bid in combination with Saquinavir SUPPLIED: Caps 100 mg; soln 80 mg/mL NOTES: Titrate dose over 1 wk to avoid GI complications; take with food; has many drug interac- tions; may cause perioral and peripheral paresthesias; store in refrigerator Rivastigmine (Exelon) COMMON USES: Mild to moderate dementia associated with Alzheimer’s disease ACTIONS: Enhances cholinergic activity DOSAGE: 1.5 mg bid; ↑ to 6 mg bid, with dosage increases at 2-wk intervals SUPPLIED: Caps 1.5, 3, 4.5, 6 mg; soln 2 mg/mL NOTES: Associated with significant dose-related GI adverse effects Rizatriptan (Maxalt) COMMON USES: Acute migraine attacks ACTIONS: Serotonin 5-HT1 receptor antagonist DOSAGE: 5–10 mg PO; may repeat once in 2 h SUPPLIED: Tabs 5, 10 mg; disintegrating tabs 5, 10 mg Rofecoxib (Vioxx) COMMON USES: Osteoarthritis, acute pain, and primary dysmenorrhea ACTIONS: NSAID; COX-2 inhibitor DOSAGE: 12.5–50 mg/d SUPPLIED: Tabs 12.5, 25 mg; susp 12.5 mg/5 mL, 25 mg/5 mL NOTES: Alert patients to be aware of GI ulceration or bleeding; use with caution in renal impair- ment; ↓ dose in elderly Rosiglitazone (Avandia) COMMON USES: Type 2 DM ACTIONS: ↑ Insulin sensitivity DOSAGE: 4–8 mg/d PO or in 2 ÷ doses 22 600 Clinician’s Pocket Reference, 9th Edition SUPPLIED: Tabs 2, 4, 8 mg NOTES: May be taken without regard to meals; do NOT use in active liver disease Salmeterol (Serevent) COMMON USES: Asthma and exercise-induced bronchospasm ACTIONS: Sympathomimetic bronchodilator DOSAGE: 2 inhal bid SUPPLIED: Met-dose inhaler; NOT for relief of acute attacks Saquinavir (Fortovase) COMMON USES: HIV infection ACTIONS: HIV protease inhibitor DOSAGE: 1200 mg PO tid within 2 h pc SUPPLIED: Caps 200 mg Sargramostim [GM-CSF] (Leukine) COMMON USES: Myeloid recovery following BMT or cancer chemotherapy ACTIONS: Activates mature granulocytes and macrophages DOSAGE: Adults & Peds. 250 mg/m2/d IV for 21 d (BMT) SUPPLIED: Inj 250, 500 mg NOTES: May cause bone pain Scopolamine, Transdermal (Transderm-Scop) COMMON USES: Prevention of nausea and vomiting associated with motion sickness ACTIONS: Anticholinergic, antiemetic DOSAGE: Apply 1 TD patch behind the ear q 3 d; 0.3–0.65 IM/IV/SC, repeat PRN q4–6h SUPPLIED: Patch 1.5 mg, injectable forms NOTES: May cause dry mouth, drowsiness, and blurred vision. Apply at least 4 h before exposure Secobarbital (Seconal) [C-II] COMMON USES: Insomnia ACTIONS: Rapid-acting barbiturate DOSAGE: Adults. 100–200 mg IM hs PRN. Peds. 3–5 mg/kg/dose IM hs PRN, up to 100 mg SUPPLIED: Inj 50 mg/mL NOTES: Beware of respiratory depression; tolerance acquired within 1–2 wk Selegiline (Eldepryl) COMMON USES: Parkinson’s disease ACTIONS: Inhibits MAO activity DOSAGE: 5 mg PO bid SUPPLIED: Tabs 5 mg NOTES: May cause nausea and dizziness Selenium Sulfide (Exsel Shampoo, Selsun Blue Shampoo, Selsun Shampoo) COMMON USES: Scalp seborrheic dermatitis, itching and flaking of the scalp due to dandruff; treat- ment of tinea versicolor ACTIONS: Antiseborrheic DOSAGE: Dandruff, seborrhea: Massage 5–10 mL into wet scalp, leave on 2–3 min, rinse and re- peat; use 2×/wk, then once q 1–4 wk PRN. Tinea versicolor: Apply qd for 7 d, 2.5% on area and lather with small amounts of water; leave on skin for 10 min, then rinse 22 SUPPLIED: Shampoo 1, 2.5% 22 Commonly Used Medications 601 Sertraline (Zoloft) COMMON USES: Depression ACTIONS: Inhibits neuronal uptake of serotonin DOSAGE: 50–200 mg/d PO SUPPLIED: Tabs 25, 50, 100 mg NOTES: Can activate manic/hypomanic state; has caused weight loss in clinical trials; caution in he- patic impairment Sibutramine (Meridia) COMMON USES: Obesity ACTIONS: Blocks uptake of norepinephrine, serotonin, and dopamine DOSAGE: 10 mg/d, may ↓ to 5 mg after 4 wk SUPPLIED: Caps 5, 10, 15 mg NOTES: Use with low-calorie diet, monitor BP Sildenafil (Viagra) COMMON USES: Erectile dysfunction ACTIONS: Smooth muscle relaxation and increased inflow of blood to the corpus cavernosum; in- hibits phosphodiesterase type 5 responsible for cGMP breakdown resulting in increased cGMP ac- tivity DOSAGE: 25–100 mg 1 h prior to attempted sexual activity, max dosing is once daily SUPPLIED: Tabs 25, 50, 100 mg NOTES: Contra with nitrates of any form; adjust dose in persons >65 y, hepatic/severe renal impair- ment, potent CYP3A4 inhibitors (ie, protease inhibitors); may cause headache, blue haze visual disturbance, usually reversible; cardiac events in the absence of nitrate use debatable Silver Nitrate (Dey-Drop) COMMON USES: Prevention of ophthalmia neonatorium due to GC; removal of granulation tissue, warts and cauterization of wounds ACTIONS: Caustic antiseptic and astringent DOSAGE: Adults & Peds. Apply to moist surface 2–3×/wk for several weeks or until desired effect. Peds. Newborns: Apply 2 gtt into conjunctival sac immediately after birth SUPPLIED: Topical impregnated applicator sticks, 10% oint, 10, 25, 50% soln; ophth 1% amp NOTES: May stain tissue black, usually resolves Silver Sulfadiazine (Silvadene) COMMON USES: Prevention of sepsis in 2nd- and 3rd-degree burns ACTIONS: Bactericidal DOSAGE: Adults & Peds. Aseptically cover the affected area with 1⁄16-in. coating bid SUPPLIED: Cream 1% NOTES: Can have systemic absorption with extensive application Simethicone (Mylicon) COMMON USES: Flatulence ACTIONS: Defoaming action DOSAGE: Adults & Peds. 40–125 mg PO pc and hs PRN SUPPLIED: Tabs 40, 80, 125 mg; caps 125 mg; gtt 40 mg/0.6 mL Simvastatin (Zocor) COMMON USES: Reduction of elevated cholesterol levels ACTIONS: HMG-CoA reductase inhibitor DOSAGE: 5–80 mg PO hs SUPPLIED: Tabs 5, 10, 20, 40 mg NOTES: Avoid concurrent use of gemfibrozil 22 602 Clinician’s Pocket Reference, 9th Edition Sirolimus [Rapamycin] (Rapamune) COMMON USES: Prophylaxis of organ rejection ACTIONS: Inhibits T-lymphocyte activation DOSAGE: 2 mg/d PO SUPPLIED: Soln 1 mg/mL NOTES: Dilute in water or orange juice; do NOT drink grapefruit juice while on sirolimus; take 4 h after cyclosporin; dosage adjustment in hepatic impairment. Routine blood levels not needed ex- cept in Peds or liver failure (trough 9–17 ng/mL) Sodium Bicarbonate Used for emergency cardiac care (see Chapter 21) COMMON USES: Alkalinization of urine, RTA, metabolic acidosis DOSAGE: Adults. Emergency cardiac care: Initiate adequate ventilation, 1 mEq/kg/dose IV ; can re- peat 0.5 mEq/kg in 10 min once or based on acid–base status. Metabolic acidosis: 2–5 mEq/kg IV over 8 h and PRN based on acid–base status. Alkalinize urine: 4 g (48 mEq) PO, then 1–2 g q4h; adjust based on urine pH. Chronic renal failure: 1–3 mEq/kg/d. Distal RTA: 1 mEq/kg/d PO. Peds. >1 y: Emergency cardiac care: See Adult. <1 y: Emergency cardiac care: Initiate adequate ventila- tion, 1:1 dilution 1 mEq/mL dosed 1 mEq/kg IV; can repeat with 0.5 mEq/kg in 10 min once or

based on acid–base status. Chronic renal failure: See Adult. Distal RTA: 2–3 mEq/kg/d PO. Proxi- mal RTA: 5–10 mEq/kg/d titrate based on serum bicarbonate levels. Urine alkalinization: 84–840 mg/kg/d (1–10 mEq/kg/d) ÷ doses; adjust based on urine pH SUPPLIED: IV inf, powder, and tabs. 300 mg = 3.6 mEq; 325 mg = 3.8 mEq; 520 mg = 6.3 mEq; 600 mg = 7.3 mEq; 650 mg = 7.6 mEq NOTES: 1 g neutralizes 12 mEq of acid; in infants, do NOT exceed 10 mEq/min inf Sodium Citrate (Bicitra) COMMON USES: Alkalinization of urine; dissolve uric acid and cysteine stones ACTIONS: Urinary alkalinizer DOSAGE: Adults: 2–6 tsp (10–30 mL) diluted in 1–3 oz water pc and hs. Peds. 1–3 tsp (5–15 mL) diluted in 1–3 oz water pc and hs SUPPLIED: 15- or 30-mL unit dose: 16 (473 mL) or 4 (118 mL) fl oz NOTES: Do NOT give to patients on aluminum-based antacids. Contra in patients with severe renal impairment of sodium-restricted diets Sodium Polystyrene Sulfonate (Kayexalate) COMMON USES: Hyperkalemia ACTIONS: Sodium and potassium ion-exchange resin DOSAGE: Adults. 15–60 g PO or 30–60 g PR q6h based on serum K+. Peds. 1 g/kg/dose PO or PR q6h based on serum K+ SUPPLIED: Powder; susp 15 g/60 mL sorbitol NOTES: Can cause hypernatremia; given with an agent, eg, sorbitol to promote movement through the bowel Sorbitol COMMON USES: Constipation ACTIONS: Laxative DOSAGE: 30–60 mL of a 20–70% soln PRN SUPPLIED: Liq 70% Sotalol (Betapace) COMMON USES: Ventricular arrhythmias ACTIONS: β-Adrenergic-blocking agent DOSAGE: 80 mg PO bid; may be ↑ to 240–320 mg/d 22 22 Commonly Used Medications 603 SUPPLIED: Tabs 80, 120, 160, 240 mg NOTES: Adjust dosage for renal insufficiency Spironolactone (Aldactone) COMMON USES: Hyperaldosteronism, essential HTN, and edematous states (CHF, cirrhosis) ACTIONS: Aldosterone antagonist; K-sparing diuretic DOSAGE: Adults. 25–100 mg PO qid. Peds. 1–3.3 mg/kg/24h PO ÷ bid–qid. Neonates: 0.5– 1 mg/kg/dose q8h SUPPLIED: Tabs 25, 50, 100 mg NOTES: Can cause hyperkalemia and gynecomastia; avoid prolonged use; diuretic of choice for cir- rhotic edema and ascites Stavudine (Zerit) COMMON USES: Advanced HIV disease ACTIONS: Reverse-transcriptase inhibitor DOSAGE: Adults. >60 kg: 40 mg bid. <60 kg: 30 mg bid SUPPLIED: Caps 15, 20, 30, 40 mg; soln 1 mg/mL NOTES: May cause peripheral neuropathy; not a cure for HIV; dosage adjustment in renal impair- ment Steroids, Systemic (see also Table 22–5, page 627) The following relates only to the commonly used systemic glucocorticoids. COMMON USES: Endocrine disorders (adrenal insufficiency), rheumatoid disorders, collagen- vascular diseases, dermatologic diseases, allergic states, edematous states (cerebral, nephrotic syndrome), immunosuppression for transplantation, hypercalcemia, malignancies (breast, lym- phomas), preoperatively (in any patient who has been on steroids in the previous year, known hypoadrenalism, preop for adrenalectomy); injection into joints/tissue ACTIONS: Glucocorticoid DOSAGE: Varies with use and institutional protocols. Adrenal insufficiency, acute (Addisonian cri- sis): Adult. Hydrocortisone: 100 mg IV q8h; then 300 mg/d ÷ q8h; convert to 50 mg PO q8h × 6 doses, taper to 30–50 mg/d ÷ bid. Peds. Hydrocortisone: 1–2 mg/kg IV; then 150–250 mg/d ÷ tid. Adrenal insufficiency, chronic (physiologic replacement): May need mineralocorticoid supplemen- tation such as Florinef Adults. Hydrocortisone 20 mg PO qAM, 10 mg PO qPM; cortisone 0.5–0.75 mg/kg/d ÷ bid; cortisone 0.25–0.35 mg/kg/d IM; dexamethasone 0.03–0.15 mg/kg/d or 0.6–0.75 mg/m2/d in ÷ q6–12h PO, IM, IV. Peds. Hydrocortisone 0.5–0.75 mg/kg/d PO tid; hydrocortisone succinate 0.25–0.35 mg/kg/d IM. Asthma, acute: Peds. Prednisolone 1–2 mg/kg/d or prednisone 1–2 mg/kg/d ÷ qd–bid for up to 5 d; prednisolone 2–4 mg/kg/d IV ÷ tid. Congenital adrenal hyper- plasia: Peds. Initially hydrocortisone 30–36 mg/m2/d PO ÷ ¹₃ dose q AM, ²₃ dose q PM; main- enance: 20–25 mg/m2/d ÷ bid. Extubation/airway edema: Dexamethasone 0.5–1 mg/kg/d IM/IV ÷ q6h, start beginning 24 h prior to extubation; continue for 4 additional doses. Immunosuppressive/ antiinflammatory: Adults & Older Peds. Hydrocortisone 15–240 mg PO, IM, IV q12h; methyl- prednisolone: 4–48 mg/d PO, taper to lowest effective dose; methylprednisolone sodium succinate 10–80 mg/d IM. Adults. Prednisone or prednisolone 5–60 mg/d PO, ÷ qd–qid. Infants and Younger Children. 2.5–10 mg/kg/d hydrocortisone PO ÷ q6–8h; 1–5 mg/kg/d IM/IV ÷ bid. Nephrotic syndrome: Peds. Prednisolone or prednisone 2 mg/kg/d PO ÷ tid–qid until urine is pro- tein-free for 5 d, use up to 28 d; for persistent proteinuria, 4 mg/kg/dose PO qod max 120 mg/d for an additional 28 d; maintenance: 2 mg/kg/dose qod for 28 d; taper over 4–6 wk (max 80 mg/d). Septic shock: Adults. Hydrocortisone 500 mg–1 g IM/IV q2–6h. Peds. Hydrocortisone 50 mg/kg IM/IV, repeat q4–24h PRN. Status asthmaticus: Adult and Peds. Hydrocortisone 1–2 mg/kg/dose IV q6h; then by 0.5–1 mg/kg q6h. Rheumatic disease: Adults. Intraarticular: Hydrocortisone ac- etate 25–37.5 mg large joint; 10–25 mg small joint; methylprednisolone acetate 20–80 mg large joint, 4–10 mg small joint. Intrabursal: Hydrocortisone acetate 25–37.5 mg. Intraganglial: Hydro- cortisone acetate 25–37.5 mg. Tendon sheath: Hydrocortisone acetate 5–12.5 mg. Perioperative steroid coverage: Hydrocortisone 100 mg IV night before surgery, 1 h preop, intraop, and 4, 8, and 22 604 Clinician’s Pocket Reference, 9th Edition 12 h postop; pod #1 100 mg IV q6h; pod #2 100 mg IV q8h; pod #3 100 mg IV q12h; pod #4 50 mg IV q12h; pod #5 25 mg IV q12h; then resume prior oral dosing if chronic use or discontinue if only perioperative coverage required. Cerebral edema: Dexamethasone 10 mg IV; then 4 mg IV q4–6h NOTES: See Table 22–5, page 627. All can cause hyperglycemia, “steroid psychosis,” adrenal sup- pression; never acutely stop steroids, especially if chronic treatment; taper dose. Hydrocortisone succinate administered systemically, acetate form intraarticular Steroids, Topical See Table 22–6 (pages 628–630) COMMON USES: Relief of inflammatory and pruritic manifestations of corticosteroid-response der- matoses ACTIONS: Corticosteroid, antiinflammatory DOSAGE: Varies with indication and formulation (See Table 22–6 (pages 628–630) for frequency of application) SUPPLIED: See Table 22–6, pages 628–630 Streptokinase (Streptase, Kabikinase) Used for emergency cardiac care (see Chapter 21) COMMON USES: Coronary artery thrombosis, acute massive PE, DVT, and some occluded vascular grafts ACTIONS: Activates plasminogen to plasmin that degrades fibrin; fibrinolytic DOSAGE: Adults. PE: Loading dose of 250,000 IU IV through a peripheral vein over 30 min, then 100,000 IU/h IV for 24–72 h. Coronary artery thrombosis: 1.5 million U IV over 60 min. DVT or arterial embolism: Load as with PE, then 100,000 IU/h for 72 h. Peds. 3500–4000 U/kg over 30 min, followed by 1000–1500 U/kg/h SUPPLIED: Powder for inj 250,000, 600,000, 750,000, 1,500,000 IU NOTES: If maintenance inf inadequate to maintain thrombin clotting time 2–5 × control, refer to the package insert, or the American Hospital Formulary Service for adjustments. Antibodies remain 3–6 mo following dose Streptomycin COMMON USES: TB or serious Enterococcus infections ACTIONS: Aminoglycoside; interferes with protein synthesis DOSAGE: 1–4 g/d IM in 1–2 ÷ doses (endocarditis); TB 15 mg/kg/d SUPPLIED: Inj 400 mg/mL NOTES: Increased incidence of vestibular toxicity; adjust dose in renal impairment Streptozocin (Zanosar) COMMON USES: Pancreatic islet cell tumors and carcinoid tumors ACTIONS: DNA–DNA (interstrand) cross-linking; DNA, RNA, and protein synthesis inhibitor DOSAGE: 1–1.5 g/m2 q 4 wk (single agent); 500 mg –1 g/m2/d for 5 d q 4–6 wk (combination regi- mens) SUPPLIED: Inj 1 g NOTES: Toxicity symptoms: Nausea and vomiting and duodenal ulcers; myelosuppression rare (20%) and mild; nephrotoxicity (proteinuria and azotemia often heralded by hypophosphatemia) can be dose-limiting. Hypo- or hyperglycemia may occur; phlebitis and pain at the site of inj may also occur. Use with caution; adjust dose in renal impairment Succimer (Chemet) COMMON USES: Lead poisoning ACTIONS: Heavy metal-chelating agent DOSAGE: Adults & Peds. 8–15 kg: 100 mg PO; 16–23 kg: 200 mg PO; 24–34 kg: 300 mg PO; 22 35–44 kg: 400 mg PO; >45 kg: 500 mg PO. Give dose noted q8h for 5 d, q12h for 14 d 22 Commonly Used Medications 605 SUPPLIED: Caps 100 mg NOTES: May cause a rash; patients should drink a lot of fluids Succinylcholine (Anectine, Quelicin, Sucostrin) COMMON USES: Adjunct to general anesthesia to facilitate endotracheal intubation and to induce skeletal muscle relaxation during surgery or mechanically supported ventilation ACTIONS: Depolarizing neuromuscular blocking agent DOSAGE: Adults. 0.6 mg/kg IV over 10–30 s, followed by 0.04–0.07 mg/kg as needed to maintain muscle relaxation. Peds. 1–2 mg/kg/dose IV, followed by 0.3–0.6 mg/kg/dose at intervals of 10–20 min SUPPLIED: Inj 20, 50, 100 mg/mL; powder for inj 100 mg, 500 mg, 1 g/vial NOTES: May precipitate malignant hyperthermia; respiratory depression or prolonged apnea may occur; many drug interactions potentiating activity of succinylcholine; observe for cardiovascular effects; use only freshly prepared solutions; ↓ in severe liver disease Sucralfate (Carafate) COMMON USES: Duodenal and gastric ulcers ACTIONS: Forms ulcer-adherent complex that protects against acid, pepsin, and bile acid DOSAGE: Adults. 1 g PO qid, 1 h prior to meals and hs. Peds. 40–80 mg/kg/d ÷ q6h SUPPLIED: Tabs 1 g; susp 1 g/10 mL NOTES: Continue treatment for 4–8 wk unless healing is demonstrated by x-ray or endoscopy; con- stipation most frequent side effect Sufentanil (Sufenta) [C-II] COMMON USES: Analgesic adjunct to maintain balanced general anesthesia ACTIONS: Potent synthetic opioid DOSAGE: Adjunctive: 1–8 µg/kg with nitrous oxide/oxygen; maintenance of 10–50 µg PRN. Gen- eral anesthesia: 8–30 µg/kg with oxygen and a skeletal muscle relaxant. Maintenance: 25–50 µg PRN. SUPPLIED: Inj 50 µg/mL NOTES: Respiratory depressant effects persisting longer than the analgesic effects; 80 times more potent than morphine Sulfacetamide (Bleph-10, Cetamide, Sodium Sulamyd) COMMON USES: Conjunctival infections ACTIONS: Sulfonamide antibiotic DOSAGE: 10% Oint apply qid and hs; soln for keratitis apply q2–3h depending on severity SUPPLIED: Oint 10%; soln 10, 15, 30% Sulfacetamide Prednisolone (Blephamide, others) COMMON USES: Steroid-responsive inflammatory ocular conditions with infection or a risk of in- fection ACTIONS: Antibiotic and antiinflammatory DOSAGE: Adult and Peds > 2 y. Apply oint to lower conjunctival sac qd–qid; soln 1–3 gtt 2–3 h while awake SUPPLIED: Oint: Sulfacetamide 10%/prednisolone 0.5%, sulfacetamide 10%/prednisolone 0.2%, sulfacetamide 10%/prednisolone 0.25%; susp: sulfacetamide 10%/prednisolone/0.25%, sulfac- etamide 10%/prednisolone 0.5%, sulfacetamide sodium 10%/prednisolone 0.2%, sulfacetamide 10% and prednisolone 0.25% NOTES: Ophth susp can be used as an otic agent Sulfasalazine (Azulfidine) COMMON USES: Ulcerative colitis ACTIONS: Sulfonamide; actions not clear 22 606 Clinician’s Pocket Reference, 9th Edition DOSAGE: Adults. Initially, 1 g tid–qid; ↑ to a max of 8 g/d in 3–4 ÷ doses; maintenance 500 mg PO qid. Peds. Initially, 40–60 mg/kg/24h PO ÷ q4–6h; maintenance 20–30 mg/kg/24h PO ÷ q6h SUPPLIED: Tabs 500 mg; EC tabs 500 mg; oral susp 250 mg/5 mL NOTES: Can cause severe GI upset; discolors urine Sulfinpyrazone (Anturane) COMMON USES: Acute and chronic gout ACTIONS: Inhibits renal tubular absorption of uric acid DOSAGE: 100–200 mg PO bid for 1 wk, then ↑ as needed to maintenance of 200–400 mg bid SUPPLIED: Tabs 100 mg; caps 200 mg NOTES: Avoid in renal impairment; take with food or antacids, take with plenty of fluids; avoid sal- icylates Sulindac (Clinoril) COMMON USES: Arthritis and pain ACTIONS: NSAID; inhibits prostaglandin synthesis DOSAGE: 150–200 mg bid SUPPLIED: Tabs 150, 200 mg Sumatriptan (Imitrex) COMMON USES: Acute treatment of migraine attacks ACTIONS: Vascular serotonin receptor agonist DOSAGE: SC: 6 mg SC as a single dose, PRN, to a max of 12 mg/24h; Oral: 25 mg, repeat in 2 h, PRN, 100 mg/d max oral dose; max 300 mg/d. Nasal spray: 1 single spray into 1 nostril, may re- peat in 2 h, max 40 mg/24hh SUPPLIED: Inj 12 mg/mL; tabs 25, 50 mg; nasal spray 5, 20 mg NOTES: May cause pain and bruising at the injection site; avoid in angina, ischemic heart disease, uncontrolled HTN, and ergot administration Tacrine (Cognex) COMMON USES: Mild to moderate dementia ACTIONS: Cholinesterase inhibitor DOSAGE: 10–40 mg PO qid, up to 160 mg/d SUPPLIED: Caps 10, 20, 30, 40 mg NOTES: May cause elevations in transaminases; monitor LFT regularly; separate doses from food Tacrolimus [FK 506] (Prograf) COMMON USES: Prophylaxis of organ rejection ACTIONS: Macrolide immunosuppressant DOSAGE: IV: 0.05–0.1 mg/kg/d as cont inf. PO: 0.15–0.3 mg/kg/d ÷ into 2 doses SUPPLIED: Caps 1, 5 mg; inj 5 mg/mL NOTES: May cause neurotoxicity and nephrotoxicity; ↓ in renal impairment; may need to ↓ in he- patic impairment Tamoxifen (Nolvadex) COMMON USES: Breast cancer (postmenopausal, estrogen receptor-positive), endometrial cancer, melanoma, reduction of breast cancer in high-risk women ACTIONS: Nonsteroidal antiestrogen; mixed agonist–antagonist effect DOSAGE: 20–40 mg/d (typically 10 mg bid or 20 mg/d) SUPPLIED: Tabs 10, 20 mg NOTES: Toxicity symptoms: Menopausal

symptoms (hot flashes, nausea, and vomiting) in pre- menopausal patients. Vaginal bleeding and menstrual irregularities. Skin rash, pruritus vulvae, 22 dizziness, headache, and peripheral edema. Acute flare of bone metastasis pain and hypercalcemia. 22 Commonly Used Medications 607 With high doses, retinopathy. Increased risk of pregnancy in sexually active premenopausal women by inducing ovulation Tamsulosin (Flomax) COMMON USES: Benign prostatic hyperplasia ACTIONS: Antagonist of α-receptors on the prostate DOSAGE: 0.4 mg/d SUPPLIED: Caps 0.4 mg; do NOT crush, chew, or open caps Tazarotene (Tazorac) COMMON USES: Facial acne vulgaris; stable plaque psoriasis up to 20% body surface area ACTIONS: Keratolytic DOSAGE: Adults & Peds > 12 y. Acne: Cleanse face, dry, and apply thin film qd hs on acne lesions. Psoriasis: Apply hs SUPPLIED: Gel 0.05, 0.1% Telmisartan (Micardis) COMMON USES: HTN ACTIONS: Angiotensin II receptor antagonists DOSAGE: 40–80 mg/d SUPPLIED: Tabs 40, 80 mg NOTES: Avoid use during PRG Temazepam (Restoril) [C-IV] COMMON USES: Insomnia ACTIONS: Benzodiazepine DOSAGE: 15–30 mg PO hs PRN SUPPLIED: Caps 7.5, 15, 30 mg NOTES: ↓ Dose in elderly Tenecteplase (TNKase) COMMON USES: Reduction of mortality associated with AMI ACTIONS: Thrombolytic; TPA DOSAGE: 30–50 mg; see following table Weight TNKase Volume TNKasea (kg) (mg) (mL) <60 30 6 ≥60–<70 35 7 ≥70–<80 40 8 ≥80–<90 45 9 ≥90 50 10 aFrom one vial of reconstituted TNKase. SUPPLIED: Inj 50 mg, reconstituted with 10 mL sterile water Teniposide [VM-26] (Vumon) COMMON USES: ALL (refractory pediatric), small-cell lung cancer, Kaposi’s sarcoma, non- Hodgkin’s lymphoma 22 608 Clinician’s Pocket Reference, 9th Edition ACTIONS: Topoisomerase II inhibitor, interfering with strand passage and DNA ligase activities of topoisomerase II. Cell cycle-specific activity late S, early G2 phase DOSAGE: 45–60 mg/m2/d × 5 d q 21 d; 120–160 mg/m2 on d 1, 3, and 5 q 21 d; 100 mg/m2 on d 1 and 2 q 3 wk; 100 mg/m2/wk SUPPLIED: Inj 10 mg/mL NOTES: Toxicity symptoms: Myelosuppression (especially leukopenia and thrombocytopenia), hy- potension, chemical phlebitis, skin rashes, HTN, hypersensitivity reactions (urticaria, flushing, rashes, or hypotension), and secondary leukemia. Adjust dose in significant renal impairment; con- sider adjustment in hepatic impairment Terazosin (Hytrin) COMMON USES: BPH and HTN ACTIONS: α-1 Blocker (blood vessel and bladder neck/prostate) DOSAGE: Initially, 1 mg PO hs; ↑ to a max of 20 mg/d PO SUPPLIED: Tabs 1, 2, 5, 10 mg; caps 1, 2, 5, 10 mg NOTES: Hypotension and syncope following first dose; dizziness, weakness, nasal congestion, pe- ripheral edema common; should be used with thiazide diuretic for HTN Terbinafine (Lamisil) COMMON USES: Onychomycosis, athlete’s foot ACTIONS: Inhibits squalene epoxidase resulting in fungal death DOSAGE: Oral: 250 mg/d PO for 6–12 wk. Topical: Apply to affected area SUPPLIED: Tabs 250 mg; cream 1% NOTES: Full clinical effect may take months due to need for new nail growth; NO occlusive dress- ings; dosage adjustment in renal impairment Terbutaline (Brethine, Bricanyl) COMMON USES: Reversible bronchospasm (asthma, COPD); inhibition of labor ACTIONS: Sympathomimetic DOSAGE: Adults. Bronchodilator: 2.5–5 mg PO qid or 0.25 mg SC; may repeat in 15 min (max 0.5 mg in 4 h). Met-dose inhaler: 2 inhal q4–6h. Premature labor: Acutely 2.5–10 mg/min/IV, gradu- ally ↑ as tolerated q 10–20 min; maintenance 2.5 – 10 mg PO q 4–6h until term; or 0.25 mg SC q 30 min. Peds. Oral: 0.05–0.15 mg/kg/dose PO tid; max 5 mg/24h SUPPLIED: Tabs 2.5, 5 mg; inj 1 mg/mL; met-dose inhaler NOTES: Caution with diabetes, HTN, hyperthyroidism; high doses may precipitate β-1-adrenergic effects Terconazole (Terazol [vaginal]) COMMON USES: Vaginal fungal infections ACTIONS: Topical antifungal DOSAGE: 1 applicatorful or 1 supp intravaginally hs for 7 d SUPPLIED: Vaginal cream 0.4%, vaginal supp 80 mg Tetanus Immune Globulin [TIG] COMMON USES: Passive immunization against tetanus for any person with a suspected contami- nated wound and unknown immunization status (Chapter 17) ACTIONS: Passive immunization DOSAGE: Adults & Peds. 250–500 U IM (higher doses if delay in initiation of therapy) SUPPLIED: Inj 250-U vial or syringe NOTES: May begin active immunization series at different inj site if required Tetanus Toxoid COMMON USES: Protection against tetanus 22 ACTIONS: Active immunization 22 Commonly Used Medications 609 DOSAGE: See Chapter 17 and Table 22–9, page 636 for tetanus prophylaxis SUPPLIED: Inj tetanus toxoid, fluid, measured in limes flocculation (Lf) units of toxoid: 4–5 Lf units/0.5 mL; tetanus toxoid, adsorbed, 5, 10 Lf units/0.5 mL Tetracycline (Achromycin V, Sumycin) COMMON USES: Broad-spectrum antibiotic treatment against Staphylococcus, Streptococcus, Chlamydia, Rickettsia, and Mycoplasma ACTIONS: Bacteriostatic; inhibits protein synthesis DOSAGE: Adults. 250–500 mg PO bid–qid. Peds >8 y. 25–50 mg/kg/24h PO q6–12h. Do NOT use in children <8 y old SUPPLIED: Caps 100, 250, 500 mg; tabs 250, 500 mg; oral susp 250 mg/5 mL NOTES: Can stain enamel and depress bone formation in children; caution with use in pregnancy; do NOT use in the presence of impaired renal function (see Doxycycline page 531) Theophylline (Theolair, Theo-Dur, Somophyllin, others) COMMON USES: Asthma, bronchospasm ACTIONS: Relaxes smooth muscle of the bronchi and pulmonary blood vessels DOSAGE: Adults. 900 mg PO ÷ q6h; SR products may be ÷ q8–12h × (maintenance). Peds. 16–22 mg/kg/24h PO ÷ q6h; SR products may be ÷ q8–12h × (maintenance) SUPPLIED: Elixir 80, 150 mg/15 mL; liq 80, 160 mg/15 mL; caps 100, 200, 250 mg; tabs 100, 125, 200, 225, 250, 300 mg; SR caps 50, 75, 100, 125, 200, 250, 260, 300 mg; SR tabs 100, 200, 250, 300, 400, 450, 500 mg NOTES: See drug levels in Table 22–7 (pages 631–634); many drug interactions; side effects in- clude nausea, vomiting, tachycardia, and seizures Thiamine [Vitamin B1] COMMON USES: Thiamine deficiency (beriberi); alcoholic neuritis; Wernicke’s encephalopathy ACTIONS: Dietary supplementation DOSAGE: Adults. Deficiency: 100 mg/d IM for 2 wk, then 5–10 mg/d PO for 1 mo. Wernicke’s en- cephalopathy: 100 mg IV in single dose, then 100 mg/d IM for 2 wk. Peds. 10–25 mg/d IM for 2 wk, then 5–10 mg/24h PO for 1 mo SUPPLIED: Tabs 5, 10, 25, 50, 100, 500 mg; inj 100, 200 mg/mL NOTES: IV thiamine administration associated with anaphylactic reaction; give IV slowly Thiethylperazine (Torecan) COMMON USES: Nausea and vomiting ACTIONS: Antidopaminergic antiemetic DOSAGE: 10 mg PO, PR, or IM qd–tid SUPPLIED: Tabs 10 mg; supp 10 mg; inj 5 mg/mL NOTES: Extrapyramidal reactions may occur 6-Thioguanine [6-TG] (Tabloid) COMMON USES: AML, ALL, CML ACTIONS: Purine-based antimetabolite (substitutes for natural purines interfering with nucleotide synthesis) DOSAGE: 2–3 mg/kg/d SUPPLIED: Tabs 40 mg NOTES: Toxicity symptoms: Myelosuppression (especially leukopenia and thrombocytopenia), nau- sea and vomiting, anorexia, stomatitis, and diarrhea. Hepatotoxicity rare; dosage adjustment in renal or hepatic impairment Thioridazine (Mellaril) COMMON USES: Psychotic disorders; short-term treatment of depression, agitation, organic brain syndrome 22 610 Clinician’s Pocket Reference, 9th Edition ACTIONS: Phenothiazine antipsychotic DOSAGE: Adults. Initially, 50–100 mg PO tid; maintenance 200–800 mg/24h PO in 2–4 ÷ doses. Peds >2 y. 0.5–3 mg/kg/24h PO in 2–3 ÷ doses SUPPLIED: Tabs 10, 15, 25, 50, 100, 150, 200 mg; oral conc 30, 100 mg/mL; oral susp 25, 100 mg/ 5 mL NOTES: Low incidence of extrapyramidal effects; may cause ventricular arrhythmias Thiothixene (Navane) COMMON USES: Psychotic disorders ACTIONS: Antipsychotic DOSAGE: Adults & Peds >12 y. Mild to moderate psychosis: 2 mg PO tid, up to 20–30 mg/d. Se- vere psychosis: 5 mg PO bid; ↑ to a max of 60 mg/24h PRN. IM use: 16–20 mg/24h ÷ bid–qid; max 30 mg/d. Peds <12 y. 0.25 mg/kg/24h PO ÷ q6–12h SUPPLIED: Caps 1, 2, 5, 10, 20 mg; oral conc 5 mg/mL; inj 2, 5 mg/mL NOTES: Drowsiness and extrapyramidal side effects most common Tiagabine (Gabitril) COMMON USES: Adjunctive therapy in treatment of partial seizures ACTIONS: Inhibition of GABA DOSAGE: Initial 4 mg/d, ↑ by 4 mg during 2nd wk; may keep increasing by 4–8 mg/d until clinical response achieved; max dose 56 mg/d SUPPLIED: Tabs 4, 12, 16, 20 mg NOTE: Use gradual withdrawal; used in combination with other anticonvulsants Ticarcillin (Ticar) COMMON USES: Infections caused by susceptible strains of gram (−) bacteria (including Kleb- siella, Proteus, E. coli, Enterobacter, P. aeruginosa, and Serratia) involving the skin, bone, respira- tory tract, urinary tract, abdomen, and septicemia ACTIONS: Bacteriocidal; inhibits cell wall synthesis DOSAGE: Adults. 3 g IV q4–6h. Peds. 200–300 mg/kg/d IV ÷ q4–6h SUPPLIED: Inj NOTES: Often used in combination with aminoglycoside; dosage adjustment in renal impairment Ticarcillin/Potassium Clavulanate (Timentin) COMMON USES: Infections caused by susceptible strains of gram (−) bacteria (including Kleb- siella, Proteus, E. coli, Enterobacter, P. aeruginosa, and Serratia) involving the skin, bone, respira- tory tract, urinary tract, abdomen, and septicemia ACTIONS: Bactericidal; inhibits cell wall synthesis DOSAGE: Adults. 3.1 g IV q4–6h. Peds. 200–300 mg/kg/d IV ÷ q4–6h SUPPLIED: Inj NOTES: Often used in combination with aminoglycosides; dosage adjustment in renal impairment Ticlopidine (Ticlid) COMMON USES: Reduces the risk of thrombotic stroke ACTIONS: Platelet aggregation inhibitor DOSAGE: 250 mg PO bid SUPPLIED: Tabs 250 mg NOTES: Administer with food; may cause neutropenia, monitor WBC and LFTs Timolol (Blocadren) COMMON USES: HTN and MI ACTIONS: Competitively blocks β-adrenergic receptors, β1, β2 DOSAGE: HTN: 10–20 mg bid, up to 60 mg/d. MI: 10 mg bid 22 SUPPLIED: Tabs 5, 10, 20 mg 22 Commonly Used Medications 611 Timolol, Ophthalmic (Timoptic) COMMON USES: Glaucoma ACTIONS: β-Blocker DOSAGE: 0.25% 1 gt bid; ↓ to qd when controlled; use 0.5% if needed; 1 gt gel qd SUPPLIED: Soln 0.25/0.5%; Timoptic XE (0.25, 0.5%) gel-forming soln Tioconazole (Vagistat) COMMON USES: Vaginal fungal infections ACTIONS: Topical antifungal DOSAGE: 1 applicatorful intravaginally hs (single dose) SUPPLIED: Vaginal oint 6.5% Tirofiban (Aggrastat) COMMON USES: Acute coronary syndrome ACTIONS: Glycoprotein IIb/IIIa inhibitor DOSAGE: Initial 0.4 µg/kg/min for 30 min, followed by 0.1 µg/kg/min SUPPLIED: Inj 50 µg/mL, 250 µg/mL NOTES: Adjust dose in renal insufficiency; use in combination with heparin Tobramycin (Nebcin) COMMON USES: Serious gram– infections, especially Pseudomonas ACTIONS: Aminoglycoside; inhibits protein synthesis DOSAGE: Adults. 1–2.5 mg/kg/dose IV q8–24h (see page 620). Peds. 2.5 mg/kg/dose IV q8h SUPPLIED: Inj 10, 40 mg/mL NOTES: Nephrotoxic and ototoxic; ↓ with renal insufficiency; monitor creatinine clearance and serum concentrations for dosage adjustments (see Table 22–7, pages 631–634, and page 620). Tobramycin Ophthalmic (AK Tob, Tobrex) COMMON USES: Ocular bacterial infections ACTIONS: Aminoglycoside antibiotic DOSAGE: 1–2 gtt q4h; oint bid–tid; if severe infections, use oint q3–4h, or 2 gtt q 30–60 min, then less frequently SUPPLIED: Oint and soln tobramycin 0.3% Tobramycin and Dexamethasone Ophthalmic (TobraDex) COMMON USES: Ocular bacterial infections associated with significant inflammation ACTIONS: Antibiotic with antiinflammatory DOSAGE: 0.3% oint apply q3–8h or soln 0.3% apply 1–2 gtt q1–4h SUPPLIED: Oint and soln tobramycin 0.3% and dexamethasone 0.1% Tocainide (Tonocard) COMMON USES: Suppression of ventricular arrhythmias, including PVCs, and ventricular tachy- cardia ACTIONS: Class IB antiarrhythmic DOSAGE: 400–600 mg PO q8h, up to 2400 mg/d SUPPLIED: Tabs 400, 600 mg NOTES: Properties similar to those of lidocaine; ↓ dose in renal failure; CNS and GI side effects common Tolazamide (Tolinase) COMMON USES: Type 2 DM ACTION: Sulfonylurea. Stimulates the release of insulin from the pancreas; increases insulin sensi- tivity at peripheral sites; reduces glucose output from the liver DOSAGE: 100–500 mg/d SUPPLIED: Tabs 100, 250, 500 mg 22 612 Clinician’s Pocket Reference, 9th Edition Tolazoline (Priscoline) COMMON USES: Persistent pulmonary vasoconstriction and HTN of the newborn, peripheral va- sospastic disorders ACTIONS: Competitively blocks α-adrenergic receptors DOSAGE: Adults. 10–50 mg IM/IV/SC qid Neonates. 1–2 mg/kg IV over 10–15 min, followed by 1–2 mg/kg/h SUPPLIED: Inj 25 mg/mL Tolbutamide (Orinase) COMMON USES: Type 2 DM ACTION: Sulfonylurea. Stimulates the release of insulin from the pancreas; increases insulin sensi- tivity at peripheral sites; reduces glucose output from the liver DOSAGE: 500–1000 mg bid SUPPLIED: Tabs 500 mg NOTES: May require dosage adjustment in hepatic impairment Tolmetin (Tolectin) COMMON USES: Arthritis and pain ACTIONS: NSAID; inhibits prostaglandin synthesis DOSAGE: 200–600 mg tid, to a max of 2000 mg/d SUPPLIED: Tabs 200, 600 mg; caps 400 mg Tolnaftate [OTC] (Tinactin) COMMON USES: Tinea pedis, tinea cruris, tinea corporis, tinea manus, tinea versicolor ACTIONS: Topical antifungal DOSAGE: Apply to area bid for 2–4 wk SUPPLIED: OTC 1% liq; gel; powder; cream; soln Tolterodine (Detrol, Detrol LA) COMMON USES: Management of overactive bladder (frequency, urgency, urge incontinence) ACTIONS: Anticholinergic DOSAGE: Detrol 1–2 mg PO bid; Detrol LA 2–4 mg/d SUPPLIED: Detrol tabs 1, 2 mg; Detrol LA tabs 2, 4 mg NOTES: Do not administer to patients with urinary retention, gastric retention,

or uncontrolled nar- row-angle glaucoma; dry mouth common side effect Topiramate (Topamax) COMMON USES: Partial onset seizures ACTIONS: Anticonvulsant DOSAGE: Total dose 400 mg/d. See product information for 8-wk titration schedule SUPPLIED: Tabs 25, 100, 200 mg; caps sprinkles 15, 25, 50 mg NOTES: May precipitate kidney stones; dosage adjustment in renal impairment Topotecan (Hycamtin) COMMON USES: Ovarian cancer (cisplatin-refractory), small-cell lung cancer, and non-Hodgkin’s lymphoma ACTIONS: Topoisomerase I inhibitor; interferes with DNA synthesis DOSAGE: 1.5 mg/m2/d as an 1-h IV inf for 5 consecutive days, repeated q 3 wk SUPPLIED: Vials containing 4 mg of lyophilized drug reconstituted in sterile water and diluted in NS or 5% dextrose NOTES: Toxicity symptoms: Myelosuppression, nausea and vomiting, diarrhea, drug fever, and skin 22 rash. ↓ Dose for renal dysfunction 22 Commonly Used Medications 613 Torsemide (Demadex) COMMON USES: Edema, HTN, CHF, and hepatic cirrhosis ACTIONS: Loop diuretic; inhibits reabsorption of sodium and chloride in the ascending loop of Henle and distal tubule DOSAGE: 5–20 mg/d PO or IV SUPPLIED: Tabs 5, 10, 20, 100 mg; inj 10 mg/mL Tramadol (Ultram) COMMON USES: Moderate to severe pain ACTIONS: Centrally acting analgesic DOSAGE: 50–100 mg PO q4–6h PRN, not to exceed 400 mg/d SUPPLIED: Tabs 50 mg NOTES: Lowers seizure threshold, tolerance or dependence may develop Trandolapril (Mavik) COMMON USES: HTN, CHF, LVD, post-AMI ACTIONS: ACE inhibitor DOSAGE: HTN: 2–4 mg/d. CHF/LVD: 4 mg/d SUPPLIED: Tabs 1, 2, 4 mg NOTES: Dosage adjustment in renal or hepatic impairment Trazodone (Desyrel) COMMON USES: Depression ACTIONS: Antidepressant; inhibits reuptake of serotonin and norepinephrine DOSAGE: Adults & Adolescents. 50–150 mg PO qd–qid; max 600 mg/d SUPPLIED: Tabs 50, 100, 150, 300 mg NOTES: May take 1–2 wk for symptomatic improvement; anticholinergic side effects Tretinoin, Systemic [Tretinoic Acid] (Vesanoid) COMMON USES: APL induction therapy ACTIONS: Differentiating agent; all trans retinoic acid DOSAGE: 45 mg/m2/d in ÷ doses for approximately 40 d SUPPLIED: Caps 10 mg NOTES: Toxicity symptoms: Cutaneous (dryness, chafing), neurologic (headache), hypertriglyc- eridemia, and treatment-related leukocytosis reported in APL, as well as “retinoic acid syndrome” Tretinoin, Topical [Retinoic Acid] (Retin-A, Avita) COMMON USES: Acne vulgaris, sun-damaged skin, some skin cancers ACTIONS: Exfoliant retinoic acid derivative DOSAGE: Adults & Peds> 12. Apply qd hs; if irritation develops, ↓ frequency SUPPLIED: Cream 0.025, 0.05, 0.1%; gel 0.01, 0.025, 0.1%; liq 0.05% NOTES: Avoid sunlight Triamcinolone and Nystatin (Mycolog-II) COMMON USES: Cutaneous candidiasis ACTIONS: Antifungal and antiinflammatory DOSAGE: Apply lightly to area bid; max 25 d SUPPLIED: Cream and oint 15, 30, 60, 120 mg NOTES: Contra in varicella Triamterene (Dyrenium) COMMON USES: Edema associated with CHF, cirrhosis ACTIONS: Potassium-sparing diuretic DOSAGE: Adults. 100–300 mg/24h PO ÷ qd–bid. Peds. 2–4 mg/kg/d in 1–2 ÷ doses 22 614 Clinician’s Pocket Reference, 9th Edition SUPPLIED: Caps 50, 100 mg NOTES: Can cause hyperkalemia, blood dyscrasias, liver damage, and other reactions; dosage ad- justment in renal or hepatic impairment Triazolam (Halcion) [C-IV] COMMON USES: Short-term management of insomnia ACTIONS: Benzodiazepine DOSAGE: 0.125–0.25 mg/d PO hs PRN SUPPLIED: Tabs 0.125, 0.25 mg NOTES: Additive CNS depression with alcohol and other CNS depressants; ↓ dose; avoid in cir- rhosis Triethanolamine (Cerumenex) COMMON USES: Cerumen removal ACTIONS: Ceruminolytic agent DOSAGE: Fill the ear canal and insert the cotton plug; irrigate with water after 15 min; repeat as needed SUPPLIED: Soln 6, 12 mL Triethylene-Triphosphoramide [Thiotepa, TESPA, TSPA] (Thioplex) COMMON USES: Hodgkin’s and non-Hodgkin’s lymphomas; leukemia; breast, ovarian, and bladder cancers (IV and intravesical therapy), preparative regimens for allogeneic and autologous BMT in high doses ACTIONS: Polyfunctional alkylating agent DOSAGE: 0.5 mg/kg q 1–4 wk, 6 mg/m2 IM or IV × 4 d q 2–4 wk, 15–35 mg/m2 by cont IV inf over 48 h; 60 mg instilled into the bladder and retained 2 h q 1–4 wk; 900–125 mg/m2 in ABMT regi- mens (the highest dose that can be administered without ABMT is 180 mg/m2); 1–10 mg/m2 (typi- cally 15 mg) IT once or twice a week; 0.8 mg/kg in 1–2 L of soln may be instilled intraperitoneally SUPPLIED: Inj 15 mg NOTES: Toxicity symptoms: Myelosuppression, nausea, vomiting, dizziness, headache, allergy, and paresthesias Trifluoperazine (Stelazine) COMMON USES: Psychotic disorders ACTIONS: Phenothiazine; blocks postsynaptic mesolimbic dopaminergic receptors in the brain DOSAGE: Adults. 2–10 mg PO bid. Peds 6–12 y. 1 mg PO qd–bid initially, then gradually ↑ up to 15 mg/d SUPPLIED: Tabs 1, 2, 5, 10 mg; oral conc 10 mg/mL; inj 2 mg/mL NOTES: ↓ Dose in elderly and debilitated patients; oral conc must be diluted to 60 mL or more prior to administration; requires several weeks for onset of effects Trifluridine (Viroptic) COMMON USES: Herpes simplex keratitis and conjunctivitis ACTIONS: Antiviral DOSAGE: 1 gt q2h (max 9 gtt/d); ↓ to 1 gt q4h after healing begins; treat up to 14 d SUPPLIED: 1% soln Trihexyphenidyl (Artane) COMMON USES: Parkinson’s disease ACTIONS: Blocks excess acetylcholine at cerebral synapses DOSAGE: 2–5 mg PO qd–qid SUPPLIED: Tabs 2, 5 mg; SR caps 5 mg; elixir 2 mg/5 mL 22 NOTES: Contra in narrow-angle glaucoma 22 Commonly Used Medications 615 Trimethobenzamide (Tigan) COMMON USES: Nausea and vomiting ACTIONS: Inhibits medullary chemoreceptor trigger zone DOSAGE: Adults. 250 mg PO or 200 mg PR or IM tid–qid PRN. Peds. 20 mg/kg/24h PO or 15 mg/kg/24h PR or IM in 3–4 ÷ doses (NOT recommended for infants) SUPPLIED: Caps 100, 250 mg; supp 100, 200 mg; inj 100 mg/mL NOTES: In the presence of viral infections, may mask emesis or mimic CNS effects of Reye’s syn- drome; may cause parkinsonian-like syndrome Trimethoprim (Trimpex, Proloprim) COMMON USES: UTI due to susceptible gram+ and gram– organisms; often used for suppression of UTI ACTIONS: Inhibits dihydrofolate reductase DOSAGE: Adults. 100 mg/d PO bid or 200 mg/d PO. Peds. 4 mg/kg/d in 2 ÷ doses SUPPLIED: Tabs 100, 200 mg; oral soln 50 mg/5 mL NOTES: ↓ Dose in renal failure Trimethoprim-Sulfamethoxazole [Co-trimoxazole] (Bactrim, Septra) COMMON USES: UTI, otitis media, sinusitis, bronchitis, and Shigella, P. carinii, and Nocardia in- fections ACTIONS: Dual effect of SMX-inhibiting synthesis of dihydrofolic acid and TMP-inhibiting dihy- drofolate reductase to impair protein synthesis DOSAGE: Adults. 1 DS tab PO bid or 5–20 mg/kg/24h (based on TMP component) IV in 3–4 ÷ doses. P. carinii: 15–20 mg/kg/d IV or PO (TMP component) in 4 ÷ doses. Nocardia: 10–15 mg/kg/d IV or PO (TMP component) in 4 ÷ doses. Peds. 8–10 mg/kg/24h (TMP) PO ÷ into 2 doses or 3–4 doses IV; do NOT use in newborns SUPPLIED: Regular tabs 80 mg of TMP and 400 mg of SMX; DS tabs 160 mg of TMP and 800 mg of SMX; oral susp 40 mg of TMP and 200 mg of SMX/ 5 mL; inj 80 mg of TMP and 400 mg of SMX/5 mL NOTES: Synergistic combination; reduce dosage in renal failure; maintain adequate hydration Trimetrexate (Neutrexin) COMMON USES: Moderate to severe PCP ACTIONS: Inhibits dihydrofolate reductase DOSAGE: 45 mg/m2 IV q24h for 21 d SUPPLIED: Inj NOTES: Administer with leucovorin 20 mg/m2 IV q6h for 24 d; use cytotoxic precautions; infuse over 60 min; ↓ in hepatic impairment Trimipramine (Surmontil) COMMON USES: Depression ACTIONS: Tricyclic antidepressant; increases synaptic concentration of serotonin and/or norepi- nephrine in CNS DOSAGE: 50–300 mg/d PO hs SUPPLIED: Caps 25, 50, 100 mg Urokinase (Abbokinase) COMMON USES: PE, DVT, restore patency to IV catheters ACTIONS: Converts plasminogen to plasmin that causes clot lysis DOSAGE: Adults & Peds. Systemic effect: 4400 IU/kg IV over 10 min, followed by 4400–6000 IU/kg/h for 12 h. Restore catheter patency: Inject 5000 IU into catheter and gently aspirate SUPPLIED: Powder for inj 5000 IU/mL, 250,000 IU vial NOTES: Do NOT use systemically within 10 d of surgery, delivery, or organ biopsy 22 616 Clinician’s Pocket Reference, 9th Edition Valacyclovir (Valtrex) COMMON USES: Herpes zoster; genital herpes ACTIONS: Prodrug of acyclovir, inhibits viral DNA replication DOSAGE: 1 g PO tid; genital herpes treatment 500 mg bid × 7 d, prophylaxis 500–1000 mg/d SUPPLIED: Caplets 500 mg NOTES: Dosage adjustment in renal impairment Valproic Acid and Divalproex (Depakene, Depakote) COMMON USES: Rx epilepsy, mania; prophylaxis of migraines ACTIONS: Anticonvulsant; increases the availability of GABA DOSAGE: Adults & Peds. Seizures: 30–60 mg/kg/24h PO ÷ tid (after initiation of 10–15 mg/dh/24h). Mania: 750 mg in 3 ÷ doses, ↑ to a max of 60 mg/kg/d. Migraines: 250 mg bid, ↑ to 1000 mg/d SUPPLIED: Valproic acid: caps 250 mg; syrup 250 mg/5 mL. Divalproex: EC tabs 125, 250, 500; caps 125 mg NOTES: Monitor LFT and follow serum levels (see Table 22–7, pages 631–634); concurrent use of phenobarbital and phenytoin may alter serum levels of these agents; ↓ dose in hepatic impairment Valrubicin (Valstar) COMMON USES: Intravesical treatment of BCG-refractory CIS when immediate cystectomy would be associated with unacceptable morbidity or mortality ACTIONS: Semisynthetic doxorubicin analogue; cytotoxic DOSAGE: 800 mg intravesically weekly for 6 wk SUPPLIED: Liq 200 mg/5 mL NOTES: Dilute 800 mg in approximately 75 mL NS; minimal systemic absorption with intact blad- der. Do NOT use within 1–2 wk of biopsy as systemic absorption can cause myelosuppression; can cause local bladder symptoms; contra with bladder capacity of < 75 mL or active UTI Valsartan (Diovan) COMMON USES: HTN ACTIONS: Angiotensin II receptor antagonist DOSAGE: 80 –160 mg/d SUPPLIED: Caps 80, 160 mg NOTES: Use with caution with K-sparing diuretics or K supplements Vancomycin (Vancocin, Vancoled) COMMON USES: Serious MRSA infections and in enterococcal endocarditis in combination with aminoglycosides in penicillin-allergic patients; oral treatment of C. difficile pseudomembranous colitis ACTIONS: Inhibits cell wall synthesis DOSAGE: Adults. 1 g IV q12h; for colitis 125–500 mg PO q6h. Peds (NOT neonates). 40 mg/ kg/24h IV in ÷ doses q6–12h SUPPLIED: Caps 125, 250 mg; powder for oral soln; powder for inj 500 mg, 1000 mg, 10 g/vial NOTES: Ototoxic and nephrotoxic; NOT absorbed orally, provides local effect in gut only; IV dose must be given slowly over 1 h to prevent “red-man syndrome”; adjust dose in renal failure (for drug levels, see Table 22–7, pages 631–634) Varicella Virus Vaccine (Varivax) COMMON USES: Prevention of varicella (chicken pox) infection ACTIONS: Active immunization DOSAGE: Adults & Peds. 0.5 mL SC, repeated in 4–8 wk SUPPLIED: Powder for inj 22 NOTES: Live virus; do NOT administer to immunocompromised 22 Commonly Used Medications 617 Vasopressin [Antidiuretic Hormone (ADH)] (Pitressin) COMMON USES: Diabetes insipidus; relief of gaseous GI tract distention; severe GI bleeding ACTIONS: Posterior pituitary hormone, potent GI vasoconstrictor DOSAGE: Adults & Peds. Diabetes insipidus: 2.5–10 U SC or IM tid–qid or 1.5–5.0 U IM q 1–3 d of the tannate. GI hemorrhage: 0.2–0.4 U/min SUPPLIED: Inj 20 U/mL NOTES: Use with caution with any vascular disease Vecuronium (Norcuron) COMMON USES: Skeletal muscle relaxation during surgery or mechanical ventilation ACTIONS: Nondepolarizing neuromuscular blocker DOSAGE: Adults & Peds. 0.08–0.1 mg/kg IV bolus; maintenance of 0.010–0.015 mg/kg after 25–40 min followed with additional doses q 12–15 min SUPPLIED: Powder for inj 10 mg NOTES: Drug interactions leading to an increased effect of vecuronium include aminoglycosides, tetracycline, and succinylcholine; fewer cardiac effects than with pancuronium Venlafaxine (Effexor) COMMON USES: Depression ACTIONS: Potentiation of neurotransmitter activity in the CNS DOSAGE: 75–375 mg/d ÷ into 2–3 equal doses SUPPLIED: Tabs 25, 37.5, 50, 75, 100 mg; ER caps 37.5, 75, 150 mg NOTES: Dosage adjustment in renal or hepatic impairment Verapamil (Calan, Isoptin) Used for emergency cardiac care (see Chapter 21) COMMON USES: Angina, essential HTN, and arrhythmias ACTIONS: Ca channel-blocker DOSAGE: Adults. Arrhythmias: See Chapter 21. Angina: 80–120 mg PO tid, up to 480 mg/24h. HTN: 80–180 mg PO tid or SR tabs 120– 240 mg PO qd to 240 mg bid. Peds. <1 y: 0.1–0.2 mg/kg IV over 2 min (may repeat in 30 min). 1–16 y: 0.1–0.3 mg/kg IV over 2 min (may repeat in 30 min); do NOT exceed 5 mg. Oral: 1–5 y: 4–8 mg/kg/d in 3 ÷ doses. >5 y: 80 mg q6–8h SUPPLIED: Tabs 40, 80, 120 mg; SR tabs 120, 180, 240 mg; SR caps 120, 180, 240, 360 mg; inj 5 mg/2 mL NOTES: Use caution with elderly patients; ↓ dose in renal or hepatic failure; constipation common Vinblastine (Velban, Velbe) COMMON USES: Hodgkin’s and non-Hodgkin’s lymphomas, mycosis fungoides, testicular cancer, choriocarcinoma, breast cancer, histiocytosis X, non-small-cell lung cancer, AIDS-related Kaposi’s sarcoma, renal cell carcinoma ACTIONS: Inhibits microtubule assembly through binding to tubulin DOSAGE: 0.1–0.5 mg/kg/wk (4–20 mg/m2) SUPPLIED: Inj 1 mg/mL

NOTES: Toxicity symptoms: Myelosuppression (especially leukopenia), nausea and vomiting (rare), constipation, neurotoxicity (similar to that listed for vincristine but less frequent), alopecia, rash; myalgia and tumor pain common; dosage adjustment in hepatic impairment Vincristine (Oncovin, Vincasar PFS) COMMON USES: ALL, breast carcinoma, sarcoma (including Ewing’s and rhabdomyosarcoma), Wilms’ tumor, Hodgkin’s and non-Hodgkin’s lymphomas, neuroblastoma, small-cell lung cancer, multiple myeloma ACTIONS: Promotes disassembly of mitotic spindle, causing metaphase arrest DOSAGE: 0.4–1.4 mg/m2 (single doses do NOT usually exceed 2 mg) SUPPLIED: Inj 1 mg/mL 22 618 Clinician’s Pocket Reference, 9th Edition NOTES: Toxicity symptoms: Neurotoxicity commonly dose-limiting, jaw pain (trigeminal neural- gia), fever, fatigue and anorexia, constipation and paralytic ileus, bladder atony, no significant myelosuppression observed with standard doses. Soft tissue necrosis possible with extravasation; dosage adjustment in hepatic impairment Vinorelbine (Navelbine) COMMON USES: Non-small-cell lung cancer (single agent or with cisplatin), breast cancer ACTIONS: Inhibits polymerization of microtubules, impairing mitotic spindle formation, semisyn- thetic vinca alkaloid DOSAGE: 30 mg/m2/wk SUPPLIED: Inj 10 mg NOTES: Toxicity symptoms: Myelosuppression (especially leukopenia), mild GI effects and infre- quent neurotoxicity (6– 29%), constipation and paresthesias (rare). Tissue damage can result from extravasation. Dosage adjustment in hepatic impairment Vitamin B1 See Thiamine (page 609) Vitamin B6 See Pyridoxine (page 596) Vitamin B12 See Cyanocobalamin (page 521) Vitamin K See Phytonadione (page 589) Warfarin (Coumadin) COMMON USES: Prophylaxis and Rx of PE and DVT, AF with embolization, other postoperative indications ACTIONS: Inhibits vitamin K-dependent production of clotting factors in the order VII-IX-X-II DOSAGE: See Table 22–10 (page 637) for anticoagulation guidelines. Adults. Individualize dose to keep INR 2.0–3.0 for most indications, for mechanical heart valves desired INR is 2.5–3.5. ACCP guidelines recommend initiation with 5 mg, unless rapid attainment of therapeutic INR is necessary (use 7.5–10 mg) if patient elderly or has other bleeding risk factors (↓). others recommend 10–15 mg PO, IM, or IV qd for 1–3 d; then maintenance, 2–10 mg/d PO, IV, or IM; follow daily INR dur- ing initial phase to guide dosage. Peds. 0.05–0.34 mg/kg/24h PO, IM, or IV. Follow PT/INR closely to adjust dosage SUPPLIED: Tabs 1, 2, 2.5, 3, 4, 5, 6, 7.5, 10 mg; inj NOTES: INR now the preferred test rather than PT; Check INR periodically on maintenance dose; beware of bleeding caused by over anticoagulation (PT >3 × control or INR >5.0– 6.0); to rapidly correct over coumadinization, use vitamin K or FFP or both; highly teratogenic; do NOT use in pregnancy. Caution patient on taking Coumadin with other medications, especially aspirin. Com- mon warfarin interactions: Potentiates acetaminophen, alcohol (with liver disease), amiodarone, cimetidine, ciprofloxacin, co-trimoxazole, erythromycin, fluconazole, flu vaccine, isoniazid, itra- conazole, metronidazole, omeprazole, phenytoin, propranolol, quinidine, tetracycline. Inhibits bar- biturates, carbamazepine, chlordiazepoxide, cholestyramine, dicloxacillin, nafcillin, rifampin, sucralfate, high vitamin K foods Witch Hazel (Tucks Pads, others) COMMON USES: After bowel movement cleansing to decrease local irritation or relieve hemor- rhoids; after anorectal surgery and episiotomy DOSAGE: Apply PRN 22 SUPPLIED: Presoaked pads, liq 22 Commonly Used Medications 619 Zafirlukast (Accolate) COMMON USES: Prophylaxis and chronic Rx of asthma ACTIONS: Selective and competitive inhibitor of leukotriene D4 and E4 DOSAGE: 20 mg bid SUPPLIED: Tabs 20 mg NOTES: NOT for acute exacerbations of asthma, contra in nursing women; associated with hepatic dysfunction, which has been reversible on discontinuation Zalcitabine [DdC] (Hivid) COMMON USES: HIV patients intolerant of zidovudine and didanosine ACTIONS: Antiretroviral agent DOSAGE: 0.75 mg PO tid SUPPLIED: Tabs 0.375, 0.75 mg NOTES: May be used in combination with zidovudine; may cause peripheral neuropathy; dosage adjustment in renal impairment Zaleplon (Sonata) COMMON USES: Insomnia ACTION: A nonbenzodiazepine sedative hypnotic, a pyrazolopyrimidine DOSAGE: 5–20 mg hs PRN SUPPLIED: Caps 5, 10 mg Zanamivir (Relenza) COMMON USES: Influenza ACTIONS: Inhibits viral neuraminidase DOSAGE: 2 inhal (10 mg) bid for 5 d SUPPLIED: Powder for inhal 5 mg NOTES: Uses a Diskhaler for administration; initiate within 48 h of symptom onset; do NOT use in pulmonary disease Zidovudine (Retrovir) COMMON USES: HIV infections ACTIONS: Inhibits reverse transcriptase DOSAGE: Adults. 200 mg PO tid or 300 mg PO bid or 1–2 mg/kg/dose IV q4h. Pregnancy: 100 mg PO 5×/d until the start of labor, then during labor 2 mg/kg over 1 h followed by 1 mg/kg/h until clamping of the umbilical cord. Peds. 160 mg/m2/dose q8h SUPPLIED: Caps 100 mg; tabs 300 mg; syrup 50 mg/5 mL; inj 10 mg/mL NOTES: Not a cure for HIV infections; hematologic toxicity; dosage adjustment in renal impair- ment Zidovudine and Lamivudine (Combivir) COMMON USES: HIV infections ACTIONS: Combination inhibitors of reverse transcriptase DOSAGE: Adults & Peds 12 y. 1 tab bid SUPPLIED: Caps zidovudine 300 mg/lamivudine 150 mg NOTES: An alternative to ↓ number of caps for combination therapy with the two agents Zileuton (Zyflo) COMMON USES: Prophylaxis and chronic treatment of asthma ACTIONS: Inhibitor of 5-lipoxygenase DOSAGE: 600 mg qid SUPPLIED: Tabs 600 mg NOTES: MUST take on a regular basis; does NOT treat acute exacerbation; hepatotoxic/do NOT use in hepatic impairment 22 620 Clinician’s Pocket Reference, 9th Edition Zolmitriptan (Zomig) COMMON USES: Acute treatment of migraine Action: Selective agonist of serotonin to cause vasoconstriction DOSAGE: Initial 2.5 mg, may repeat after 2 h to a max of 10 mg in 24 h NOTES: Use with caution in hepatic impairment; do NOT use in PRG Zolpidem (Ambien) [C-IV] COMMON USES: Short-term treatment of insomnia ACTIONS: Hypnotic agent DOSAGE: 5–10 mg PO hs PRN SUPPLIED: Tabs 5, 10 mg Zonisamide (Zonegran) COMMON USES: Partial seizures ACTIONS: Anticonvulsant DOSAGE: Initial 100 mg/d; may be ↑ to 400 mg/d SUPPLIED: Caps 100 mg NOTES: Contra in persons with hypersensitivity to sulfonamides Aminoglycoside Dosing Table 22–7 (pages 631–634) gives information on the trough and peak levels of the amino- glycosides gentamicin, tobramycin, and amikacin. Peak levels should be drawn 30 min after the dose is completely infused; trough levels should be drawn 30 min prior to the dose. As a general rule, draw the peak and trough around the fourth maintenance dose. Therapy can be initiated with the recommended guidelines that follow. Procedure (Adult) 1. Calculate estimated CrCl based on SCr, age, and weight (in kg), or a formal CrCl can also be ordered, if time permits. 2. Select loading dose: Gentamicin: 1.5–2.0 mg/kg Tobramycin: 1.5–2.0 mg/kg Amikacin: 5.0–7.5 mg/kg 3. By using Table 22–8 (page 635), select maintenance dose (as a percentage of the cho- sen loading dose) most appropriate for the renal function of patient based on the CrCl and dosing interval. Shaded areas are suggested percentages and intervals for any given CrCl. This is only an empiric dose to begin therapy. Monitor serum levels routinely for optimal therapy. Use Table 22–7 (pages 631–634) for the drug levels to follow for each drug. IMMUNIZATION SCHEDULE (SEE TABLE 22–9, PAGE 636) Perform active immunization of normal infants and children based on Table 22–9 (page 636). In addition, perform TB tine test at 15–19 mo and again at the entry to school (4–6 y). Hep B = hepatitis B vaccine; DtaP = diphtheria and tetanus toxoids and acellular pertussis vaccine. Td = Tetanus toxoid. Hib = Haemophilus influenza type b vaccine. IPV = all- inactivated polio virus vaccine. MMR = measles-mumps-rubella vaccine. Var = varicella. Hep A = hepatitis A vaccine. For additional details refer to MMWR Vol 50, No 01; Jan 12, 2001. 22 22 621 TABLE 22–1 Quick Guide to Dosing of Acetaminophen Based on the Tylenol Product Line Suspension* Regular† Drops and Suspension* Junior* Strength Extra Strength† Original Drops Chewable* Liquid and Strength 160 325 mg 500 mg 80 mg/0.8 ml Tablets 80 Original Elixir mg Caplets/ Caplets/ Caplets/ Dropperful mg tabs 160 mg/5 ml Chewables Tablets Gelcaps Q–3 mo/6–11 lb/2.5–5.4 kg ¹₂ dppr‡ (0.4 mL) 4–11 mo/12–17 lb/5.5–7.9 kg 1 dppr‡ (0.8 mL) ¹₂ tsp 12–23 mo/18–23 lb/8.0–10.9 kg 1¹₂ dppr‡ (1.2 mL) ³₄ tsp 2–3 y/24–35 lb/11.09–15.9 kg 2 dppr‡ (1.6 mL) 2 tab 1 tsp 4–5 y/36–47 lb/16.0–21.9 kg 3 tab 1¹₂ tsp 6–8 y/48–59 lb/22.0–26.9 kg 4 tab 2 tsp 2 cap/tab 9–10 y/60–71 lb/27.0–31.9 kg 5 tab 2¹₂ tsp 2¹₂ cap/tab 11 y/72–95 lb/32.0–43.9 kg 6 tab 4 tsp 3 cap/tab Adults & children 12 y and 4 cap/tab 1 or 2 2 caps/gel over/96 lb and over/44.0 kg caps/tabs and over *Doses should be administered 4 or 5 times daily or as directed by your doctor. Do not exceed 5 doses in 24 h. †No more than 8 dosage units in any 24-h period. Not to be taken for pain for more than 10 days or for fever for more than 3 days unless directed by a physician. ‡Dropperful. 622 Clinician’s Pocket Reference, 9th Edition TABLE 22–2 Comparison of Insulins Onset Peak Duration Type of Insulin (h) (h) (h) Ultra Rapid Humalog (Lispro) Immediate 0.5–1.5 3–5 NovoLog (Insulin aspart) Immediate 0.5–1.5 3–5 Rapid Regular Iletin II 0.25–0.5 2.0–4.0 5–7 Humulin R 0.5 2.5–4.0 6–8 Novolin R 0.5 2.0–5.0 5–8 Velosulin 0.5 2.0–5.0 6–8 Intermediate NPH Iletin II 1.0–2.0 6–12 18–24 Lente Iletin II 1.0–2.0 6–12 18–24 Humulin N 1.0–2.0 6–12 14–24 Novulin L 2.5–5.0 7–15 18–24 Novulin 70/30 0.5 7–12 24 Prolonged Ultralente 4.0–6.0 14–24 28–36 Humulin U 4.0–6.0 8–20 24–28 Lantus (insulin glargine) 4.0–6.0 No peak 24 Combination Insulins Humalog Mix (lispro protamine/ lispro) 0.25–0.5 1–4 24 22 22 623 TABLE 22–3 Some Oral Contraceptives Drug (Manufacturer) Estrogen (µg)* Progestin (mg)† MONOPHASICS Alesse 21, 28 (Wyeth-Ayerst) Ethinyl estradiol (20) Desogestrel (0.15) Brevicon 21, 28 (Watson)‡ Ethinyl estradiol (35) Norethindrone (0.5) Demulen 1/35 21 (Searle)‡ Ethinyl estradiol (35) Ethynodiol diacetate (1) Demulen 1/50 21 (Searle)‡ Ethinyl estradiol (50) Ethynodiol diacetate Desogen (Organon) Ethinyl estradiol (30) Desogestrel (0.15) Genora 1/50 28 (Physicians total care) Mestranol (50) Norethindrone (1) Genora 1/35 21, 28 (Physicians total care) Ethinyl estradiol (35) Norethindrone (1) Levlen 21, 28 (Berlex) Ethinyl estradiol (30) Levonorgestrel (0.15) Levlite 21, 28 (Berlex) Ethinyl estradiol (20) Levonorgestrel (0.1) Levora 21, 28 (Watson) Ethinyl estradiol (30) Levonorgestrel (0.15) Loestrin 1.5/30 21, 28 (Parke-Davis) Ethinyl estradiol (30) Norethindrone acetate (1.5) Loestrin 1/20 21, 28 (Parke-Davis) Ethinyl estradiol (20) Norethindrone acetate (1) Lo/Ovral (Wyeth-Ayerst)‡ Ethinyl estradiol (30) Norgestrel (0.3) Low-Ogestrel (Watson) Ethinyl estradiol (30) Norgestrel (0.3) Modicon 28 (Ortho-McNeil) Ethinyl estradiol (35) Norethindrone (0.5) Necon 1/50 21, 28 (Watson) Mestranol (50) Norethindrone (1) Necon 0.5/35E 21, 28 (Watson) Ethinyl estradiol (35) Norethindrone (0.5) Necon 1/35 21, 28 (Watson) Ethinyl estradiol (35) Norethindrone (1) Nelova 0.5/35E 21 (Warner-Chilcott)‡ Ethinyl estradiol (35) Norethindrone (0.5) Nelova 1/35 21 (Warner-Chilcott) Ethinyl estradiol (35) Norethindrone (1) Nelova 1/50 21 (Warner-Chilcott)‡ Mestranol (50) Norethindrone (1) Nordette-21 (Wyeth-Ayerst)‡ Ethinyl estradiol (30) Levonorgestrel (0.15) Norinyl 1/35 21, 28 (Watson) Ethinyl estradiol (35) Norethindrone (1) Norinyl 1/50 21, 28 (Watson) Mestranol (50) Norethindrone (1) (continued ) 22 624 TABLE 22–3 (Continued) Drug Estrogen (µg)* Progestin (mg)† Ogestrel-28 (Watson) Ethinyl estradiol (50) Norgestrel (0.5) Ortho-Cept 21 (Ortho-McNeil)‡ Ethinyl estradiol (30) Desogestrel (0.15) Ortho-Cyclen 21 (Ortho-McNeil)‡ Ethinyl estradiol (35) Norgestimate (0.25) Ortho-Novum 1/35 21 (Ortho-McNeil)‡ Ethinyl estradiol (35) Norethindrone (1) Ortho-Novum 1/50 21 (Ortho-McNeil)‡ Mestranol (50) Norethindrone (1) Ovcon 35 21, 28 (Warner Chilcott) Ethinyl estradiol (35) Norethindrone (0.4) Ovcon 50 21, 28 (Warner Chilcott) Ethinyl estradiol (50) Norethindrone (1) Ovral (Wyeth-Ayerst)‡ Ethinyl estradiol (50) Norgestrel (0.5) Zovia 1/50E 21, 28 (Watson) Ethinyl estradiol (50) Ethynodiol diacetate (1) Zovia 1/35E 21, 28 (Watson) Ethinyl estradiol (35) Ethynodiol diacetate (1) BIPHASICS Jenest-28 (Organon) Ethinyl estradiol (35) Norethindrone (0.5, 1) Necon 10/11 21, 28 (Watson) Ethinyl estradiol (35) Norethindrone (0.5, 1) Nelova 10/11 21 (Warner-Chilcott) Ethinyl estradiol (35) Norethindrone (0.5, 1) Ortho-Novum 10/11 21 (Ortho-McNeil)‡ Ethinyl estradiol (35, 35) Norethindrone (0.5, 1.0) TRIPHASICS§ Estrostep 28 (Parke-Davis) Ethinyl estradiol (20, 30, 35) Norethindrone acetate (1) Mircette 28 (Organoon) Ethinyl estradiol (20, 0, 10) Desogestrel (0.15) Ortho Tri-Cyclen (Ortho-McNeil)‡ Ethinyl estradiol (35, 35, 35) Norgestimate (0.18, 0.215, 0.25) (continued ) 22 625 TABLE 22–3 (Continued) Drug Estrogen (µg)* Progestin (mg)† Ortho-Novum 7/7/7 21 (Ortho-McNeil)‡ Ethinyl estradiol (35, 35, 35) Norethindrone (0.5, 0.75, 1.0) Tri-Levlen 21, 28 (Berlex) Ethinyl estradiol (30, 40, 30) Levonorgestrel (0.05, 0.075, 0.125) Tri-Norinyl 21, 28 (Watson) Ethinyl estradiol (35, 35, 35) Norethindrone (0.5, 1.0, 0.5) Triphasil–21 (Wyeth-Ayerst)‡ Ethinyl estradiol (30, 40, 30) Levonorgestrel (0.05, 0.075, 0.125) Trivora-28 (Watson) Ethinyl estradiol (30, 40, 30) Levonorgestrel (0.05, 0.075, 0.125) PROGESTIN ONLY Micronor (Ortho-McNeil) None Norethindrone (0.35) Nor-QD (Watson) None Norethindrone (0.35) Ovrette (Wyeth-Ayerst) None Norgestrel (0.075) *Ethinyl estradiol and mestranol are not equivalent milligram for milligram; the results of some

studies indicate that 35 µg of ethinyl estradiol is equivalent to 50 mg of mestranol. †Different progestins are not equivalent milligram for milligram. ‡Also available in a 28-day regimen at slightly different cost. §Estrogen/progesterone dose varies based on the time of the cycle (ie, days 1–7, 8–14, 15–21). 626 Clinician’s Pocket Reference, 9th Edition TABLE 22-4 Some Common Oral Potassium Supplements (see page 592) meq potassium/ Brand Name Salt Form Dosing Unit Glu-K Gluconate Tablet 2 meq/tablet Kaochlor 10% KCl Liquid 20 meq/15 mL Kaochlor S-F 10% KCl Liquid 20 meq/15 mL (sugar-free) Kaochlor Eff Bicarbonate/KCl/ Effervescent citrate tablet 20 meq/tablet Kaon elixir Gluconate Liquid 20 meq/mL Kaon Gluconate Tablets 5 meq/tablet Kaon-Cl KCl Tablet, SR 6.67 meq/tablet Kaon-Cl 20% KCl Liquid 40 meq/15 mL KayCiel KCl Liquid 20 meq/15 mL K-Lor KCl Powder 15 or 20 meq/packet Klorvess Bicarbonate/KCl Liquid 20 meq/15 mL Klotrix KCl Tablet, SR 10 meq/tablet K-Lyte Bicarbonate/ Effervescent citrate tablet 25 meq/tablet K-Tab KCl Tablet, SR 10 meq/tablet Micro-K KCl Capsules, 8 meq/capsule SR Slow-K KCl Tablet, SR 8 meq/tablet Tri-K Acetate/bicar- Liquid 45 meq/15 mL bonate and citrate Twin-K Citrate/gluconate Liquid 20 meq/5 mL Abbreviation: SR = sustained release. 22 22 Commonly Used Medications 627 TABLE 22–5 Comparison of Systemic Steroids (see page 603) Relative Equivalent Mineralocorticoid Duration Drug Dose (mg) Activity (h) Route Betamethasone 0.75 0 36–72 PO, IM Cortisone 25.00 2 8–12 PO, IM (Cortone) Dexamethasone 0.75 0 36–72 PO, IV (Decadron) Hydrocortisone 20.00 2 8–12 PO, IM, (Solu-Cortef, IV Hydrocortone) Methylprednisolone 4.00 0 36–72 PO, IM, acetate IV (Depo-Medrol) Methylprednisolone 4.00 PO, IM, succinate IV (Solu-Medrol) Prednisone 5.00 1 12–36 PO (Deltasone) Prednisolone 5.00 1 12–36 PO, IM, (Delta-Cortef) IV 22 22 628 TABLE 22–6 Topical Steroid Preparations (See page 604 for additional information) Agent Common Trade Names Potency Apply Aclometasone dipropionate Aclovate, cream, oint 0.05% Low bid/tid Amcinonide Cyclocort, cream, lotion, oint 0.1% High bid/tid Betamethasone Betamethasone valerate Valisone cream, lotion 0.01% Low qd/bid Betamethasone valerate Valisone cream, 0.01, 0.1%, Intermediate qd/bid oint, lotion 0.1% Betamethasone dipropi- Diprosone cream (0.05%) High qd/bid onate Diprosone aerosol (0.1%) Betamethasone dipropi- Diprolene oint, gel Ultra high qd/bid onate, augmented 0.05% Clobetasol propionate Temovate cream, gel, oint, Ultra high bid (2 wk max) scalp, soln 0.05% Clocortolone pivalate Cloderm cream 0.1% Intermediate qd–qid Desonide DesOwen, cream, oint, lotion 0.05% Low bid–qid Desoximetasone Desoximetasone 0.05% Topicort LP cream, gel 0.05% Intermediate Desoximetasone 0.25% Topicort cream, oint High Dexamethasone base Aeroseb-Dex aerosol 0.01% Low bid–qid Decadron cream 0.1% Diflorasone diacetate Psorcon cream, oint 0.05% Ultrahigh bid/qid Fluocinolone Fluocinolone acetonide 0.01% Synalar cream, soln 0.01% Low bid/tid (continued ) 22 629 TABLE 22–6 (Continued) Agent Common Trade Names Potency Apply Fluocinolone acetonide 0.025% Synalar oint, cream 0.025% Intermediate bid/tid Fluocinolone acetonide 0.2% Synalar-HP cream 0.2% High bid/tid Fluocinonide 0.05% Lidex, anhydrous cream, gel, High bid/tid oint soln 0.05% Lidex-E aqueous cream 0.05% Flurandrenolide Cordran cream, oint 0.025% Intermediate bid/tid cream, lotion, oint 0.05% Intermediate bid/tid tape, 4 µg/cm2 Intermediate qd Fluticasone propionate Activate cream 0.05%, oint 0.005% Intermediate bid Halobetasol Cutivate cream, oint 0.05% Very High bid Halcinonide Halog cream 0.025%, emollient base High qd/tid 0.1% cream, oint, solution 0.1% Hydrocortisone Hydrocortisone Cortisone, Caldecort, Hycort, Hytone, Low tid/qid etc. aerosol 1%, cream: 0.5, 1,2.5%, gel 0.5% oint 0.5, 1, 2.5%, lotion 0.5, 1, 2.5% paste 0.5% soln 1% Hydrocortisone acetate Corticaine cream, oint 0.5, 1% Low tid/qid Hydrocortisone butyrate Locoid oint, soln 0.1% Intermediate bid/tid Hydrocortisone valerate Westcort cream, oint 0.2% Intermediate bid/tid oint, lotion 0.025% (continued ) 22 630 TABLE 22–6 (Continued) Agent Common Trade Names Potency Apply Mometasone furoate Elocon 0.1% cream, oint, lotion Intermediate qd Prednicarbate Dermatop 0.1% cream Intermediate bid Triamcinolone Triamcinolone acetonide 0.025% Aristocort, Kenalog cream, Low tid/qid Triamcinolone acetonide 0.1% Aristocort, Kenalog cream, Intermediate tid/qid oint, lotion 0.1% Aerosol 0.2 mg/2-sec spray Triamcinolone acetonide 0.5% Aristocort, Kenalog cream, High tid/qid oint 0.5% 22 631 TABLE 22–7 Common Drug Levels Therapeutic Usual Potentially Toxic Drug When to Sample Levels Half-life Levels ANTIBIOTICS Gentamicin Peak: 30 min after 30-min infusion Peak: 5–8 µg/mL 2 h Peak: >12 µg/mL (peak level not necessary Trough <2 mg/mL if extended interval dosing: <1.0 µg/mL for ext- 6 mg/kg/dose) tended intervals (6 mg/kg/dose) Trough: <0.5 h before next dose Peak levels not needed with extended-interval dosing Tobramycin Same as above Same as above Same as above Amikacin Same as above Peak: 20–30 µg/mL 2 h Peak: >35 µg/mL Vancomycin Peak: 1 h after 1 h-infusion Peak: 30–40 µg/mL 6–8 h Peak: >50 µg/mL Trough: <0.5 h before next dose Trough: >15 µg/mL ANTICONVULSANTS Carbamazepine Trough: just before next oral dose 8–12 µg/mL (monotherapy) 15–20 h Trough: >12 µg/mL 4–8 µg/mL (polytherapy) Ethosuximide Trough: just before next oral dose 40–100 µg/mL 30–60 h Trough: >100 µg/mL Phenobarbital Trough: just before next dose 15–40 µg/mL 40–120 h Trough: >40 µg/mL Phenytoin Use free phenytoin to monitor 5–12 µg/mL Concentration- >2 µg/mL Trough: just before next dose dependent (continued ) 22 632 TABLE 22–7 (Continued) Therapeutic Usual Potentially Toxic Drug When to Sample Levels Half-life Levels Trough just before next dose 5–12 µg/mL 10–12 h >12 µg/mL (note-primidone is metabolized Primidone to phenobarb. Order levels separately) Valproic acid Trough: just before next dose 50–100 µg/mL 5–20 h >100 µg/mL BRONCHODILATORS Caffeine Trough: just before next dose Adults 5–15 µg/mL Adults 3–4 h 20 µg/mL Neonate 6–11 mg/mL Neonates 30– 140 h IV: 12–24 h after infusion started 5–15 µg/mL Nonsmoking adult-8 h >20 µg/mL Theophylline (IV) Children and smoking adults -4 h Theophylline (PO) Peak levels: not recommended 5–15 µg/mL Trough level: just before next dose CARDIOVASCULAR AGENTS Amiodarone Trough: just before next dose 1–2.5 µg/mL 30–100 days >2.5 µg/mL (continued ) 22 633 TABLE 22–7 (Continued) Therapeutic Usual Potentially Toxic Drug When to Sample Levels Half-life Levels Digoxin Trough: just before next dose 0.8–2.0 ng/mL 36 h >2 ng/mL (levels drawn earlier than 6 h after a dose will be artificially elevated) Disopyramide Trough: just before next dose 2–5 µg/mL 4–10 h >5 µg/mL Flecainide Trough: just before next dose 0.2–1.0 µg/mL 11–14 h >1.0 µg/mL Lidocaine Steady-state levels are usually 1.2–5.0 µg/mL 1.5 h >6 µg/mL achieved after 6–12 h Procainamide Trough: just before next oral dose 4–10 µg/mL Procaine: 3–5 h >10 µg/mL NAPA + Procain: NAPA: 6–10 h >30 µg/mL 5–30 µg/mL (NAPA + Procain) Quinidine Trough: just before next oral dose 2–5 µg/mL 6 h 0.5 µg/mL OTHER AGENTS Amitriptyline plus Trough: just before next dose 120–250 ng/mL nortriptyline Nortriptyline Trough: just before next dose 50–140 ng/mL Lithium Trough: just before next dose 0.5–1.5 meq/mL 18–20 h >1.5 meq/mL Imipramine Trough: just before next dose 150–300 ng/mL plus desipramine Desipramine Trough: just before next dose 50–300 ng/mL Methotrexate By protocol <0.5 µmol/L after 48 h (continued ) 22 634 TABLE 22–7 (Continued) Therapeutic Usual Potentially Toxic Drug When to Sample Levels Half-life Levels Cyclosporine Trough: just before next dose Highly variable Highly variable Renal: 150–300 ng/mL (RIA) Hepatic: 150– 300 ng/mL Doxepin Trough: just before next dose 100–300 ng/mL Trazodone Trough: just before next dose 900–2100 ng/mL *Results of therapeutic drug monitoring must be interpreted in light of the complete clinical situation. For information on dosing or interpretation of drug levels contact the pharmacist or an order for a pharmacokinetic consult may be written in the patient’s chart. Based on data from Pharmacy and Therapeutics Commit- tee Formulary, 41st edition, Thomas Jefferson University Hospital, Philadelphia, PA. 22 Commonly Used Medications 635 TABLE 22–8 Percentage of Loading Dose Required for Dosage Interval Chosen for Aminoglycosides (see page 620 for dosing information) CrCl Dosing Interval (mL/min) 8 h 12 h 24 h 90 90 –– — 90 88 –– — 70 84 –– — 60 79 91 — 50 74 87 — 40 66 80 –– 30 57 72 92 25 51 66 88 20 45 54 83 15 37 50 75 10 29 40 64 7 24 33 55 5 20 28 48 2 14 20 35 0 9 13 25 Source: Based on data from Hull JH, Sarubbi FA: Gentamicin serum concentrations: Phar- macokinetic predictions. Ann Intern Med 1976;85:183–189. Shaded boxes indicate sug- gested dosage intervals. Abbreviation: CrCl = creatinine clearance. 22 22 636 TABLE 22–9 Recommended Childhood Immunization Schedule (United States, January–December 2001) AGE 1 2 4 6 12 15 18 24 4–6 11–12 14–18 VACCINE Birth mo mo mo mo mo mo mo mo y y y Hepatitis B† (Hep B) Hep B #1 Hep B #2 Hep B #3 Hep B Diphtheria and tetanus toxoids (Td) and pertussis§ (DTaP) DTaP DTaP DTaP DTaP DTaP Td Haemophilus influenzae type b¶ (Hib) Hib Hib Hib Hib Inactivated polio** (IPV) IPV IPV IPV IPV Pneumococcal†† conjugate (PCV) PCV PCV PCV PCV Measles–mumps– rubella§§ (MMR) MMR MMR MMR Varicella¶¶ (Var) Var VVaarr Hepatitis A*** (Hep A) Hep A in selected areas Source: MMWR Vol. 50/No. 1, Jan. 12, 2001. Range of recommended ages for vaccination. Vaccines to be given if previously recommended doses were missed or were given earlier than the recommended minimum age. Recommended in selected states and/or regions. See text for abbreviations. 22 Commonly Used Medications 637 TABLE 22–10 Oral Anticoagulant Standards of Practice (see Warfarin, page 618) Thromboembolic Disorder INR Duration Deep Venous Thrombosis Prophylaxis (high-risk surgery) 2–3 <3 mo or until ambulatory Treatment: single episode 2–3 3–6 mo Recurrent systemic embolism 2–3 Indefinite Prevention of Systemic Embolism Atrial fibrillation (AF) 2–3 Indefinite AF: cardioversion 2–3 3 wk prior; 4 wk post sinus rhythm Valvular heart disease 2–3 Indefinite Cardiomyopathy 2–3 Indefinite Acute Myocardial Infarction Prevention of systemic embolization 2–3 <3 mo Prevention of recurrence 2.5–3.5 Indefinite Prosthetic Valves Tissue heart valves 2–3 3 mo Bileaflet mechanical valve in aortic 2–3 Indefinite position Other mechanical prosthetic valvesa 2.5–3.5 Indefinite Source: Based on data published in Chest 1998;114 Supplement 439S–769S. aMay add aspirin 81 mg to warfarin in patients with ball–cage valves or with additional risk factors. Abbreviation: INR: international normalized ratio. 22 This page intentionally left blank. APPENDIX Apgar Scores Measurements Body Surface Area Equivalents Adult SI Prefixes and Symbols Children Performance Status Scales Body Weights, Desirable Radiation Terminology Cancer Screening Temperature Conversion Recommendations TNM and Other Systems of Epidemiology Basics Classification for Common Tumors Glasgow Coma Scale Weight Conversion APGAR SCORES Apgar scores (Table A–1) are a numerical expression of a newborn infant’s physical condi- tion. Usually determined 1 min after birth and again at 5 min, the score is the sum of points gained on assessment of color, heart rate, reflex irritability, muscle tone, and respirations. BODY SURFACE AREA Adult Figure A–1 is a nomogram for determining the body surface area of an adult. Children Figure A–2 is a nomogram for determining the body surface area of children. BODY WEIGHTS, DESIRABLE Table A–2 gives desirable body weights for men and women. CANCER SCREENING RECOMMENDATIONS Table A–3 lists the recommendations from the American Cancer Society for cancer screen- ing programs in average risk, asymptomatic people. These are the recommendations of the ACS and may not be supported by other organizations. EPIDEMIOLOGY BASICS Number of persons who have a disease at one point in time Prevalence = Number of persons at risk at that point (continued on page 645) 639 Copyright 2002 The McGraw-Hill Companies, Inc. Click Here for Terms of Use 640 Clinician’s Pocket Reference, 9th Edition TABLE A–1 Apgar Scores Score Sign 0 1 2 Appearance (color) Blue or pale Pink body with Completely blue extremities pink Pulse (heart rate) Absent Slow (<100/min) >100/min Grimace (reflex No response Grimace Cough or sneeze irritability Activity (muscle tone) Limp Some flexion Active movement Respirations Absent Slow, irregular Good, crying TABLE A–2 Desirable Weights (in lb) for Men and Women* Age Height 19–34 35 Years and Older 5’0” 97–128 108–138 5’1” 101–132 111–143 5’2” 104–137 115–148 5’3” 107–141 119–152 5’4” 111–146 122–157 5’5” 114–150 126–162 5’6” 118–156 130–167 5’7” 121–160 134–172 5’8” 125–164 138–178 5’9” 129–169 142–183 5’10” 132–174 146–188 5’11” 136–179 151–194 6’0” 140–184 155–199 6’1” 144–189 159–205 6’2” 148–195 164–210 *Weights are based on weighing in without shoes or clothes. Source: United States Department of Agriculture and United States Department of Health and Human Resources, 1990. Appendix 641 FIGURE A–1 Body surface area: Adult. Use a straight edge to connect the height and mass. The point of intersection on the body surface line gives the body surface area (in m2).

(Reprinted, with permission, from: Lentner C [ed]: Geigy Scientific Ta- bles, 8th ed. Ciba-Geigy, San Francisco CA, 1981, Vol. 1, p. 226.) 642 Clinician’s Pocket Reference, 9th Edition FIGURE A–2 Body surface area: Child. Use a straight edge to connect the height and mass. The point of intersection on the body surface line gives the body surface area (in m2). (Reprinted, with permission, from: Lentner C [ed]: Geigy Scientific Ta- bles, 8th ed. Ciba-Geigy, San Francisco CA, 1981, Vol. 1, p. 227.) 643 TABLE A–3 Recommendations for Cancer Screening for Average Risk, Asymptomatic People Cancer Site Population Test or Procedure Frequency Breast Women, age 20+ Breast self-examination Monthly, starting at age 20 Clinical breast examination Every 3 years, ages 20–39 Annual, starting at age 40* Mammography Annual, starting at age 40 Colorectal Men & women, Fecal occult blood test & Annual fecal occult blood test and flexible sigmoid- age 50+ flexible sigmoidoscopy† oscopy at age 50; thereafter, fecal occult blood test every year and flexible sigmoidoscopy every 5 years -or- Double contrast barium enema† Double contrast barium enema at age 50; thereafter, every 5–10 y -or- Colonoscopy† Colonoscopy every 10 y starting at age 50 Prostate Men, age 50+ Digital rectal examination & Annual digital rectal examination and prostate-specific prostate specific antigen test antigen test should be offered to men starting at age 50‡ Cervix Women, age 18+ Pap test and pelvic examination All women who are, or have been, sexually active, or have reached age 18 should have an annual Pap test and pelvic examination. After a woman has had 3 or more consecutive satisfactory normal annual examinations, the Pap test may be per- formed less frequently at the discretion of the physi- cian. (continued ) 644 TABLE A–3 (Continued) Cancer Site Population Test or Procedure Frequency Cancer- Men & women Examinations every 3 y from ages 20–39 y and annually after age 40. The cancer- related age 20+ related check-up should include examination for cancers of the thyroid, testicles, check-up ovaries, lymph nodes, oral cavity, and skin, as well as health counseling about tobacco, sun exposure, diet and nutrition, risk factors, sexual practices, and environmental and occupational exposures. *Beginning at age 40, annual clinical breast examination should be performed prior to mammography. †Digital rectal examination should be performed at the time of sigmoidoscopy, barium enema, and colonoscopy. ‡Information should be provided to men regarding potential risks and benefits of screening. Source: Reprinted, with permission, from Cancer J Clin 2000:50;39. Appendix 645 (continued from page 639) Number of new cases of a disease over a period of time Incidence = Number of persons at risk during that period Sensitivity = Proportion of subjects with the disease who have a positive test = (a/a + c) Specificity = Proportion of subjects without the disease who have a negative test = (d/b + d) Predictive value = Positive: likelihood of a positive test indicates disease = (a/a + b) = Negative: likelihood of a negative test indicates lack of disease = (d/c + d) Disease + (Present)
(Absent) (+) a b Test (
) c d GLASCOW COMA SCALE The Glasgow Coma Scale (EMV Scale) gives a fairly reliable, objective way to monitor changes in levels of consciousness. It is based on Eye opening, Motor responses, and Verbal responses. A person’s EMV score is based on the total of the three responses. The score ranges from 3 (lowest) to 15 (highest) (Table A–4). TABLE A–4 Glasgow Coma Scale Parameter Response Score Eyes Open: Spontaneously 4 To verbal command 3 To pain 2 No response 1 Best motor response To verbal command Obeys 6 To painful stimulus Localized pain 5 Flexion-withdrawal 4 Decorticate (flex) 3 Decerebrate (extend) 2 No response 1 Best verbal response Oriented, converses 5 Disoriented, converses 4 Inappropriate responses 3 Incomprehensible sounds 2 No response 1 646 Clinician’s Pocket Reference, 9th Edition MEASUREMENTS Equivalents (Approximate) Length 1 centimeter (cm) = 0.4 in. 1 meter (m) = 39.4 in. Household 1 teaspoon (tsp) = 5 mL 1 tablespoon (tbsp) = 15 mL 1 ounce (oz) = 30 mL 8 ounces (oz) = 1 cup = 240 mL 1 quart (qt) = 946 mL Apothecary 1 grain (gr) = 60 mg 30 gram (g) = 1 oz 1 g = 15 gr SI PREFIXES AND SYMBOLS Factor Prefix Symbol 109 giga G 106 mega M 103 kilo k 102 hecto h 101 deka da 10–1 deci d 10–2 centi c 10–3 milli m 10–6 micro µ 10–9 nano n 10–12 pico p 10–15 femto f PERFORMANCE STATUS SCALES Table A–5 lists the most common performance scales used clinically. RADIATION TERMINOLOGY Measure Old Term SI Unit Activity curie becquerel (Bq) Absorbed dose rad gray (Gy) TEMPERATURE CONVERSION Table A–6 gives information for converting temperature from the Fahrenheit (F) scale to the centigrade, or Celsius (C), scale and vice versa. (continued on page 649) 647 TABLE A–5 Performance Status Scales Karnofsky ECOG AJCC Functional % Normal Activity Activity Status Status Level Grade Level Grade Activity Able to carry on normal 100 Normal; no complaints; 0 Normal activity H0 Normal activity activity; no special no evidence of disease; care needed 90 Able to carry on normal activity; minor sign or symptoms of disease 80 Normal activity with effort; 1 Symptoms but H1 Symptomatic and some signs or symptoms ambulatory ambulatory; cares for of disease self Unable to work; able to 70 Cares for self; unable to live at home; cares for carry on normal activity most personal needs; or progressing rapidly varying amount of to active work assistance needed 60 Requires occasional 2 In bed 50% H2 Ambulatory 50% of time; assistance but able of time occasionally needs to care for self assistance 50 Requires considerable assistance and frequent medical care (continued ) 648 TABLE A–5 (Continued) Karnofsky ECOG AJCC Functional % Normal Activity Activity Status Status Level Grade Level Grade Activity Unable to care for self; 40 Disabled; requires special 3 In bed 50% H3 Ambulatory 50% of time; requires equivalent care and assistance of time nursing care of needed institutional or hospital care; may 30 Severely disabled; hospital- be progressing rapidly ization indicated through death not imminent 20 Very sick; hospitalization 4 100% bedridden H4 Bedridden; may need necessary hospitalization 10 Moribund; fatal processes 0 Dead Abbreviations: ECOG = Eastern Cooperative Oncology Group; AJCC = American Joint Committee on Cancer. Source: Reprinted, with permission, from Practical Oncology. Cameron R (ed). Appleton & Lange, Stamford, CT, 1993. Appendix 649 TABLE A–6 Temperature Conversion Table F C C F 0 −17.7 0 32.0 95.0 35.0 35.0 95.0 96.0 35.5 35.5 95.9 97.0 36.1 36.0 96.8 98.0 36.6 36.5 97.7 98.6 37.0 37.0 98.6 99.0 37.2 37.5 99.5 100.0 37.7 38.0 100.4 101.0 38.3 38.5 101.3 102.0 38.8 39.0 102.2 103.0 39.4 39.5 103.1 104.0 40.0 40.0 104.0 105.0 40.5 40.5 104.9 106.0 41.1 41.0 105.8 C = (F − 32) × 5/9 F = (C × 9/5) + 32 Abbreviations: F = degrees Fahrenheit; C = degrees Celsius. TNM AND OTHER SYSTEMS OF CLASSIFICATION FOR COMMON TUMORS TNM stands for “tumor, nodes, metastasis” and is a universally accepted classification sys- tem for malignancy staging. The UICC (Union Internationale Contre le Cancer) and the AJCC (American Joint Committee on Cancer) have adopted this system and have published this system in TNM Classification of Malignant Tumours, 5th ed John Wiley & Sons, New York, 1997. The following is a highly selected listing of commonly encountered solid tumors (breast, bladder, cervix, colon and rectum, kidney, lung, melanoma, ovary, stomach, thyroid, uterus, and prostate) as well as the classification for lymphomas. Where appropri- ate, other common staging systems are noted (ie, Duke’s classification of colon cancer) TNM CLASSIFICATION Breast Primary Tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ: Intraductal carcinoma, lobular carcinoma in situ, or Paget’s disease of the nipple with no tumor. Note: Paget disease associated with a tumor is classified according to the size of the tumor. T1 Tumor 2 cm or less in greatest dimension T1mic Microinvasion 0.1 cm or less in greatest dimension T1a More than 0.1 cm but not more than 0.5 cm in greatest dimension 650 Clinician’s Pocket Reference, 9th Edition T1b More than 0.5 cm but not more than 1 cm in greatest dimension T1c More than 1 cm but not more than 2 cm in greatest dimension T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension T3 Tumor more than 5 cm in greatest dimension T4 Tumor of any size with direct extension to chest wall or skin T4a Extension to chest wall T4b Edema (including peau d’orange) or ulceration of the skin of breast or satel- lite skin nodules confined to same breast T4c Both T4a and T4b T4d Inflammatory carcinoma Lymph Node (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph nodes(s) N2 Metastasis to ipsilateral axillary lymph node(s) fixed to one another or to other struc- tures N3 Metastasis to ipsilateral internal mammary lymph node(s) Distant Metastasis (M) MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis (includes metastasis to ipsilateral supraclavicular lymph nodes) Pathologic Classification (pTNM) Primary Tumor (pT) The pT categories correspond to the T categories. Regional Lymph Nodes (pN) pNX Regional lymph nodes cannot be assessed pN0 No regional lymph node metastasis pN1 Metastasis to movable ipsilateral axillary lymph node(s) pN1a Only micrometastasis (none larger than 0.2 cm) pN1b Metastasis to lymph nodes, any larger than 0.2 cm pN1bi Metastasis in 1–3 lymph nodes, any more than 0.2 cm and all less than 2 cm in greatest dimension pN1bii Metastasis to 4 or more lymph nodes, any more than 0.2 cm and all less than 2 cm in greatest dimension pN1biii Extension of tumor beyond the capsule of a lymph node metasta- sis less than 2 cm in greatest dimension pN1biv Metastasis to a lymph node 2 cm or more in greatest dimension pN2 Metastasis to ipsilateral axillary nodes that are fixed pN3 Metastasis to ipsilateral internal mammary lymph nodes(s) Pathologic Classification The pM category corresponds to the M category above. Bladder Primary Tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ: “flat tumor” Appendix 651 Ta Noninvasive papillary carcinoma T1 Tumor invades subepithelial connective tissue T2 Tumor invades muscle T2a Tumor invades superficial muscle (inner half) T2b Tumor invades deep muscle (outer half) T3 Tumor invades perivesical tissue T3a Microscopically T3b Macroscopically (extravesical mass) T4 Tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall T4a Tumor invades prostate or uterus or vagina T4b Tumor invades pelvic wall or abdominal wall Lymph Node (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in a single lymph node, 2 cm or less in greatest dimension N2 Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension, or multiple lymph nodes, none more than 5 cm in greatest dimension N3 Metastasis in a lymph node more than 5 cm in greatest dimension Distant Metastasis (M) MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Pathologic Classification (pTNM) The pT, pN, and pM categories correspond to the T, N , and M categories. Cervix Primary Tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ T1 Cervical carcinoma confined to uterus T1a Preclinical invasive carcinoma diagnosed by microscopy only T1ai Stromal invasion no greater than 3.0 mm in depth and 7.0 mm or less in horizontal spread T1aii Stromal invasion more than 3.0 mm and not more than 5.0 mm with a horizontal spread 7.0 mm or less T1b Clinically visible lesion confined to the cervix or microscopic lesion greater than T1a2 T1bi Clinically visible lesion 4 cm or less in greatest dimension T1bii Clinically visible lesion more than 4 cm in greatest dimension T2 Cervical carcinoma invades beyond uterus but not to pelvic wall or to the lower third of vagina T2a Tumor without parametrial invasion T2b Tumor with parametrial invasion T3 Cervical carcinoma extends to pelvic

wall and/or involves lower third of vagina and/or causes hydronephrosis or nonfunctioning kidney T3a Tumor involves lower third of the vagina, no extension to pelvic wall 652 Clinician’s Pocket Reference, 9th Edition T3b Tumor extends to pelvic wall and/or causes hydronephrosis or nonfunctioning kidney T4 Tumor invades mucosa of bladder or rectum and/or extends beyond the true pelvis Note: The presence of bullous edema is not sufficient to classify a tumor as T4. Lymph Node (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant Metastasis (M) MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Pathologic Classification (pTNM) The pT, pN and pM categories correspond to the T, N , and M categories. Colon and Rectum Primary Tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ: intraepithelial or invasion of lamina propria* T1 Tumor invades submucosa T2 Tumor invades muscularis propria T3 Tumor invades through muscularis propria into subserosa, or into nonperitonealized pericolic or perirectal tissues T4 Tumor perforates visceral peritoneum or directly invades other organs or structures Lymph Node (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in 1– 3 pericolic or perirectal lymph nodes N2 Metastasis in 4 or more pericolic or perirectal lymph nodes Distant Metastasis (M) MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Pathologic Classification (pTNM) The pT, pN and pM categories correspond to the T, N , and M categories. DUKES’ CLASSIFICATION (ASTER–COLLER MODIFICATION) OF COLON CANCER STAGE A: Into muscularis propria, nodes negative STAGE B1: Extends through entire wall, nodes negative STAGE B2: Extends into muscularis propria, nodes positive STAGE C1: Extends through entire wall, 1–3 nodes positive *Tis includes cancer cells confined within the glandular basement membrane (intraepithelial) or lamina propria (intramucosal) with no extension through muscularis mucosa into submucosa. Appendix 653 STAGE C2: ≥ 4 nodes positive STAGE D: Metastatic disease Kidney Primary Tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor 7 cm or less in greatest dimension limited to the kidney T2 Tumor more than 7 cm in greatest dimension limited to the kidney T3 Tumor extends into major veins or invades adrenal gland or perinephric tissues but not beyond Gerota’s fascia T3a Tumor invades adrenal gland or perinephric tissues but not beyond Gerota’s fascia T3b Tumor grossly extends into renal vein(s) or vena cava below diaphragm T3c Tumor grossly extends into vena cava above diaphragm T4 Tumor invades beyond Gerota’s fascia Lymph Node (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in a single regional lymph node N2 Metastasis in more than one regional lymph node Distant Metastasis (M) MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Pathologic Classification (pTNM) The pT, pN and pM categories correspond to the T, N , and M categories. Lung Primary Tumor (T) TX Primary tumor cannot be assessed, or tumor proven by presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus T2 Tumor with any of the following features of size or extent: More than 3 cm in greatest dimension; involves main bronchus, 2 cm or more distal to the carina; invades the vis- ceral pleura; associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung T3 Tumor of any size that directly invades any of the following: chest wall (including su- perior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor in the main bronchus less than 2 cm distal to the carina but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung T4 Tumor of any size that invades any of the following: mediastinum, heart, great ves- sels, trachea, esophagus, vertebral body, carina; or tumor with a malignant pleural ef- fusion 654 Clinician’s Pocket Reference, 9th Edition Lymph Node (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, including direct extension N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s) N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s) Distant Metastasis (M) MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Pathologic Classification (pTNM) The pT, pN and pM categories correspond to the T, N , and M categories. ANN ARBOR STAGING CLASSIFICATION Lymphoma (Hodgkin’s Disease and Non-Hodgkin’s Lymphoma) STAGE DEFINITION I Limited to one area II Involvement of two or more areas on the same side of the diaphragm III Involvement of two or more areas on both sides of the diaphragm III1 Upper abdomen, spleen, splenic and hilar nodes III2 Lower abdominal nodes IV Extra lymph node involvement Melanoma of the Skin (Excluding Eyelid) Primary Tumor (pT) pTX Primary tumor cannot be assessed pT0 No evidence of tumor pTis Melanoma in situ (atypical melanotic hyperplasia, severe melanotic dysplasia), not an invasive lesion (Clark’s level I) pT1 Tumor 0.75 mm or less in thickness and invades the papillary dermis (Clark’s level II) pT2 Tumor more than 0.75 mm but not more than 1.5 mm in thickness and/or invades to papillary–reticular dermal interface (Clark’s level III) pT3 Tumor more than 1.5 mm but not more than 4 mm in thickness and/or invades the reticular dermis (Clark’s level IV) pT3a Tumor more than 1.5 mm but not more than 3 mm in thickness pT3b Tumor more than 3 mm but not more than 4 mm in thickness pT4 Tumor more than 4 mm in thickness and/or invades the subcutaneous tissue (Clark’s level V) and/or satellite(s) within 2 cm of the primary tumor pT4a Tumor more than 4 mm in thickness and/or invades the subcutaneous tissue pT4b Satellite(s) with 2 cm of primary tumor Lymph Node (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis Appendix 655 N1 Metastasis 3 cm or less in greatest dimension in any regional lymph node(s) N2 Metastasis more than 3 cm in greatest dimension in any regional lymph node(s) N2a Metastasis more than 3 cm in greatest dimension in any regional lymph node(s) and/or in-transit metastasis N2b In-transit metastasis N2c Both (N2a and N2b) Distant Metastasis (M) MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis M1a Metastasis in skin or subcutaneous tissue or lymph node(s) beyond the regional lymph nodes M1b Visceral metastasis Ovary Primary Tumor (T) TNM FIGO* DEFINITION TX Primary tumor cannot be assessed T0 I No evidence of primary tumor T1 Tumor limited to ovaries T1a Ia Tumor limited to one ovary; capsule intact, no tumor on ovarian surface T1b Ib Tumor limited to both ovaries; capsules intact, no tumor on ovarian surface T1c Ic Tumor limited to one or both ovaries with any of the following: capsule ruptured, tumor on ovarian surface, malignant cells in as- cites, or peritoneal washings T2 II Tumor involves one or both ovaries with pelvic extension T2a IIa Extension or implants on uterus or tubes T2b IIb Extension to other pelvic tissues T2c IIc Pelvic extension (2a or 2b) with malignant cells in ascites or peri- toneal washing T3 III Tumor involves one or both ovaries with microscopically con- firmed and/or N1 peritoneal metastasis outside the pelvis or re- gional lymph node metastasis T3a IIIa Microscopic peritoneal metastasis beyond pelvis T3b IIIb† Macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension T3c IIIc Peritoneal metastasis beyond pelvis more than 2 cm in greatest and/or N1 dimension or regional lymph node metastasis Lymph Node (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis *FIGO = Fédération Internationale de Gynécologie et d’Obstétrique. †Liver capsule metastasis is T3/stage III, liver parenchymal metastasis M1/stage IV. Pleural effusion must have positive cytology for M1/stage IV. 656 Clinician’s Pocket Reference, 9th Edition Distant Metastasis (M) TNM FIGO DEFINITION MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 IV Distant metastasis (excludes peritoneal metastasis) Stomach Primary Tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ: Intraepithelial tumor without invasion of lamina propria T1 Tumor invades lamina propria or submucosa T2 Tumor invades muscularis propria or subserosa T3 Tumor penetrates serosa (visceral peritoneum) without invasion of adjacent structures T4 Tumor invades adjacent structures Lymph Node (N) NX Regional lymph node(s) cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in 1–6 regional lymph node(s) N2 Metastasis in 7–15 regional lymph nodes(s) N3 Metastasis in more than 15 regional lymph nodes(s) Distant Metastasis (M) MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Pathologic Classification (pTNM) The pT, pN and pM categories correspond to the T, N, and M categories. Thyroid Gland Primary Tumor (T) All categories may be subdivided: (a) solitary; (b) multifocal–measure the largest for classi- fication TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor 1 cm or less in greatest dimension limited to the thyroid T2 Tumor more than 1 cm but not more than 4 cm in greatest dimension limited to the thyroid T3 Tumor more than 4 cm in greatest dimension limited to the thyroid T4 Tumor of any size extending beyond the thyroid capsule Lymph Node (N) Regional nodes are the cervical and upper mediastinal lymph nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis N1a Metastasis in ipsilateral cervical lymph nodes N1b Metastasis in bilateral, midline, or contralateral cervical or mediastinal lymph nodes Distant Metastasis (M) MX Presence of distant metastasis cannot be assessed Appendix 657 M0 No distant metastasis M1 Distant metastasis Pathologic Classification (pTNM) The pT, pN, and pM categories correspond to the T, N, and M categories. Uterus Primary Tumor (T) TNM FIGO DEFINITION TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis 0 Carcinoma in situ T1 I Tumor confined to corpus T1a Ia Tumor limited to endometrium T1b Ib Tumor invades up to less than one half of myometrium T1c Ic Tumor invades up to more than one half of myometrium T2 II Tumor invades cervix but does not extend beyond uterus T2a IIa Endocervical glandular involvement only T2b IIb Cervical stomal invasion T3 III Local and/or regional spread as specified in T3a, b, N1, and FIGO IIIA, B, C. T3a IIIa Tumor involves serosa and/or adnexa (direct extension or metasta- sis) and/or cancer cells in ascites or peritoneal washings T3b IIIb Vaginal involvement ( direct extension or metastasis) N1 IIIc Metastasis to pelvic and/or paraaortic lymph nodes T4* IVa Tumor invades bladder mucosa and/or bowel mucosa Lymph Node (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant Metastasis (M) TNM FIGO† DEFINITION MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Ivb Distant metastasis (excluding metastasis to vagina, pelvic serosa, or adnexa, including metastasis to intraabdominal lymph nodes other than paraaortic and/or inguinal nodes) Pathologic Classification (pTNM) The pT, pN, and pM categories correspond to the T, N, and M categories. Prostate T0 No evidence of primary tumor T1 Nonpalpable disease (old stage “A”) T1a Three or fewer microscopic foci of carcinoma T1b More than 3 microscopic foci of carcinoma T1c No palpable tumor, diagnosed by elevated PSA *The presence of bullous edema is not sufficient evidence to classify a tumor T4. †FIGO = Fédération Internationale de Gynécologie et d’Obstétrique 658 Clinician’s Pocket Reference, 9th Edition T2 Tumor presents clinically or grossly, limited to the gland (old stage “B”) T2a Tumor involves one lobe T2b Tumor involves both lobes T3 Tumor extends through the prostatic capsule (old stage “C”) T3a Extracapsular

extension (unilateral or bilateral) T3b Tumor invades seminal vesical(s) T4 Tumor is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall. Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant Metastasis (M) MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis M1a Nonregional lymph node(s) M1b Bone(s) M1c Other site(s) Pathologic Classification (pTNM) The pT, pN and pM categories correspond to the T, N, and M categories. However, there is no pT1 category because there is insufficient tissue to assess the highest pT category. WEIGHT CONVERSION Table A–7 gives information for converting weight in pounds (lb) to weight in kilograms (kg) and vice versa. TABLE A–7 Weight Conversion Table lb kg kg lb 1 0.5 1 2.2 2 0.9 2 4.4 4 1.8 3 6.6 6 2.7 4 8.8 8 3.6 5 11.0 10 4.5 6 13.2 20 9.1 8 17.6 30 13.6 10 22.0 40 18.2 20 44.0 50 22.7 30 66.0 60 27.3 40 88.0 70 31.8 50 110.0 80 36.4 60 132.0 90 40.9 70 154.0 100 45.4 80 176.0 150 68.2 90 198.0 200 90.8 100 220.9 kg = lb × 0.454 lb = kg × 2.2 INDEX NOTE: Page numbers followed by f indicate figures; those followed by t indicate tables. A Aceon (perindopril erbumine), indications, Abacavir (Ziagen), indications, actions, actions, and dosage of, 587–588 and dosage of, 488 Acetaminophen (Datril; Tylenol) Abbokinase (urokinase), indications, antidote for, 471 actions, and dosage of, 615 indications, actions, and dosage of, 488, Abciximab (ReoPro) 621t for emergency cardiac care, 464 route, effects, and dosage for, 321t indications, actions, and dosage of, 488 Acetaminophen + butalbital +/- caffeine Abdominal computed tomography, 330 (Fioricet; Medigesic; Phrenilin Abdominal distention, differential Forte; Repan; Sedapap-10 Two- diagnosis of, 42 dyne; Triapin Axocet), indications, Abdominal magnetic resonance imaging, actions, and dosage of, 489 332 Acetaminophen + codeine (Tylenol No. 1, Abdominal pain, differential diagnosis of, No. 2, No. 4), indications, actions, 42 and dosage of, 489 Abdominal paracentesis, 296–297, 298f Acetazolamide (Diamox) Abdominal ultrasound, 329 for hyperphosphatemia, 192 Abdominal x-rays, 326 indications, actions, and dosage of, 489 Abelcet (amphotericin B lipid complex), Acetic acid + aluminum acetate (Otic indications, actions, and dosage of, Domeboro), indications, actions, 497 and dosage of, 489 Abscesses, dental, 470 Acetoacetate, laboratory diagnosis and, 55 Absorbable sutures, 345, 346t Acetone, laboratory diagnosis and, 55 Acalculous cholecystitis, 434 Acetylcysteine (Mucomyst; Mucosil), 364 Acanthocytes, 104 indications, actions, and dosage of, Acarbose (Precose), indications, actions, 489–490 and dosage of, 488 N-Acetylcysteine, for acetaminophen Accelerations, in fetal heart rate, 276 poisoning, 471 Accolate (zafirlukast), indications, actions, Achromycin V (tetracycline) and dosage of, 619 indications, actions, and dosage of, Accupril (quinapril), indications, actions, 153t, 609 and dosage of, 596 interaction with enteral nutrition, 223 Accutane (isotretinoin), indications, Acid-base disorders, 163–175 actions, and dosage of, 555–556 blood gas interpretation and, 163, Acebutolol (Sectral), indications, actions, 165–166 and dosage of, 488 definition of, 163, 164t, 165f 659 Copyright 2002 The McGraw-Hill Companies, Inc. Click Here for Terms of Use 660 Index Acid-base disorders (continued ) Activated clotting time (ACT), 105 hypoxia, 171f, 171–172 Activated partial thromboplastin time metabolic acidosis, 164t, 166–167 (aPTT), 107 metabolic alkalosis, 164t, 167, 169 Actonel (risedronate), indications, actions, mixed, 163 and dosage of, 599 respiratory acidosis, 164t, 169–170 Actos (pioglitazone), indications, actions, respiratory alkalosis, 164t, 170–171 and dosage of, 589 sample problems involving, 172–175 Actretin (Soriatane), indications, actions, simple, 163 and dosage of, 488 Acid-fast stain, 121 Acular (ketorolac, ophthalmic), Acidosis indications, actions, and dosage of, metabolic, 164t, 166–167 557 respiratory, 164t, 169–170 Acupuncture, for pain management, 323 Acid phosphatase, laboratory diagnosis Acute abdominal series, 326 and, 55 Acute coronary syndromes algorithm, Acinetobacter, Gram stain characteristics 459f of, 125t, 126t Acute intravascular hemolysis, 202 Aciphex (rabeprazole), indications, Acute lung injury, transfusions and, 202, actions, and dosage of, 597 203 Aclovate (aclometasone dipropionate), Acute renal failure, 432–433 potency and application of, 628t diet for, 207t Acne, organisms responsible and empiric Acute specimens (titers), 132 therapy for, 141t Acute tubular necrosis, 432 Acne rosacea, organisms responsible and Acyclovir (Zovirax), indications, actions, empiric therapy for, 141t and dosage of, 147t, 148t, 149t, Acquired immunodeficiency syndrome. 490 See Human immunodeficiency Adalat (nifedipine), indications, actions, virus (HIV) infection; Human and dosage of, 578 immunodeficiency virus (HIV) Adalat CC (nifedipine), indications, testing actions, and dosage of, 578 ACTH stimulation test, 55–56 Adapin (doxepin) Actidose (activated charcoal) half-life and therapeutic and toxic levels clinical use of, 472 of, 634t indications, actions, and dosage of, 514 indications, actions, and dosage of, 530 Actimmune (interferon gamma-1B), Adenosine (Adenocard) indications, actions, and dosage of, for emergency cardiac care, 461 554 indications, actions, and dosage Actinomyces, Gram stain characteristics of, 490 of, 125t Adrenalin. See Epinephrine (Adrenalin; Actiq (fentanyl, transmucosal system), Sus-Phrine) indications, actions, and dosage of, Adrenal masses, differential diagnosis of, 538 42 Activase (alteplase, recombinant) Adrenal scans, 333 for emergency cardiac care, 466 α1-Adrenergic blockers, 479 indications, actions, and dosage of, Adrenergic nervous system, 395, 397, 492–493 397t, 398t Activated charcoal (Actidose; Liqui-Char; Adrenocorticotropic hormone (ACTH), Superchar) laboratory diagnosis and, 55 clinical use of, 472 Adriamycin (doxorubicin), indications, indications, actions, and dosage of, 514 actions, and dosage of, 531 Index 661 Adrucil (fluorouracil), indications, indications, actions, and dosage of, actions, and dosage of, 540 502 Adult respiratory distress syndrome AK Spore HC Ophthalmic (bacitracin, (ARDS), 429–431 neomycin, polymyxin B, + Advanced cardiac life support (ACLS), hydrocortisone, ophthalmic), 449–468 indications, actions, and dosage of, algorithms for, 450f–460f 502 drugs used in, 449, 461–467 AK Spore Ophthalmic (bacitracin, electrical defibrillation and neomycin, + polymyxin B, cardioversion for, 467–468 ophthalmic), indications, actions, transcutaneous pacing for, 468 and dosage of, 502 Advil (Ibuprofen) AK Tob (tobramycin, ophthalmic), indications, actions, and dosage of, 551 indications, actions, and dosage of, route, effects, and dosage for, 321t 611 Aerobid (flunisolide), indications, actions, AK-Tracin Ophthalmic (bacitracin, and dosage of, 540 ophthalmic), indications, actions, Aeromonas hydrophilia, Gram stain and dosage of, 502 characteristics of, 126t Alanine aminotransferase (ALT; SGPT), Aeroseb-Dex (dexamethasone base), laboratory diagnosis and, 57 potency and application of, 628t Albalon-A Opthalmic (naphazoline + Aerosol therapy, 363 antazoline), indications, actions, topical medications for, 364 and dosage of, 575 AFB smear, 121 Albendazole, indications for, 153t, 154t Afrinol (pseudoephedrine), indications, Albumin, blood levels of, laboratory actions, and dosage of, 595–596 diagnosis and, 56 Afterload, 395 Albumin (Albuminar; Albutein; measurement of, 410 Buminate), indications, actions, Agenerase (amprenavir), indications, and dosage of, 200t, 490 actions, and dosage of, 150t, 498 Albumin/globulin ratio (A/G ratio), Aggrastat (tirofiban) laboratory diagnosis and, 56 for emergency cardiac care, 464 Albuterol (Proventil; Ventolin), 364 indications, actions, and dosage of, 611 for anaphylaxis, 469 AIDS. See Human immunodeficiency indications, actions, and dosage of, 490 virus (HIV) infection; Human nebulized, for asthmatic attacks, 469 immunodeficiency virus (HIV) Albuterol + ipratropium (Combivent), testing indications, actions, and dosage of, Air-contrast BE, 328 490 AK-Beat (levobunolol), indications, Aldactazide (hydrochlorothiazide + actions, and dosage of, 560 spironolactone), indications, AK-DEX Ophthalmic (dexamethasone, actions, and dosage of, 549 ophthalmic), indications, actions, Aldactone (spironolactone), indications, and dosage of, 524 actions, and dosage of, 603 Akne-Mycin Topical (erythromycin, Aldara (imiquimod), indications, actions, topical), indications, actions, and and dosage of, 148t, 552 dosage of, 534 Aldesleukin [IL-2] (Proleukin), AK-NEO-DEX Ophthalmic (neomycin + indications, actions, and dosage of, dexamethasone), indications, 491 actions, and dosage of, 576 Aldomet (methyldopa), indications, AK Poly Bac Ophthalmic (bacitracin + actions, and dosage of, 569 polymyxin B, ophthalmic), Aldosterone, laboratory diagnosis and, 56 662 Index Alendronate (Fosamax), indications, Alprostadil [prostaglandin E1] (Prostin actions, and dosage of, 491 VR), indications, actions, and Alesse 21, 28, 623t dosage of, 492 Aleve (naproxen), indications, actions, and Alprostadil, intracavernosal (Caverject; dosage of, 575575 Edex), indications, actions, and Alfentanil (Alfenta), indications, actions, dosage of, 492 and dosage of, 491 Alprostadil, urethral suppository (Muse), Alginic acid + aluminum hydroxide and indications, actions, and dosage of, magnesium trisilicate (Gaviscon), 492 indications, actions, and dosage of, Altace (ramipril) 491 for emergency cardiac care, 461 Alimentum, 224t indications, actions, and dosage of, 597 Alkaline phosphatase, laboratory Alteplase, recombinant [TPA] (Activase) diagnosis and, 56–57 for emergency cardiac care, 466 Alkalinization, for poisoning, 472 indications, actions, and dosage of, Alkalosis 492–493 metabolic, 164t, 167, 169 AlternaGel (aluminum hydroxide) respiratory, 164t, 170–171 for hyperphosphatemia, 192 Alka-Mints (calcium carbonate) indications, actions, and dosage of, 493 for hypocalcemia, 190 Altretamine (Hexalen), indications, indications, actions, and dosage actions, and dosage of, 493 of, 508 Alum (ammonium aluminum sulfate), Alkeran (melphalan), indications, actions, indications, actions, and dosage of, and dosage of, 566 496 Alkylating agents, 478 Aluminum carbonate (Basaljel) Allegra (fexofenadine), indications, for hyperphosphatemia, 192 actions, and dosage of, 538–539 indications, actions, and dosage of, 493 Allergic reactions Aluminum hydroxide (ALternaGel; to latex, 344 Amphojel) medications for, 476 for hyperphosphatemia, 192 to transfusions, 202, 203 indications, actions, and dosage of, 493 Allopurinol (Aloprim; Lopurin; Aluminum hydroxide + magnesium Zyloprim), indications, actions, carbonate (Gaviscon), indications, and dosage of, 491 actions, and dosage of, 493 Alomide Ophthalmic (lodoxamide), Aluminum hydroxide + magnesium indications, actions, and dosage of, hydroxide (Maalox), indications, 562 actions, and dosage of, 493–494 Alopecia, differential diagnosis of, 42 Aluminum hydroxide + magnesium Aloprim (allopurinol), indications, trisilicate (Gaviscon; Gaviscon-2), actions, and dosage of, 491 indications, actions, and dosage of, Alosetran (Iotronex), indications, actions, 493 and dosage of, 491 Alupent (metaproterenol), 364 Alpha-fetoprotein (AFP), laboratory indications, actions, and dosage of, 567 diagnosis and, 57 Amantadine (Symmetrel), indications, Alphagan (brimonidine), indications, actions, and dosage of, 148t, 494 actions, and dosage of, 506 Amaryl (glimepiride), indications, actions, Alpha-1 receptors, 397 and dosage of, 545 Alprazolam (Xanax), indications, actions, Ambien (zolpidem), indications, actions, and dosage of, 492 and dosage of, 620 Index 663 Ambisome (amphotericin B liposomal), Amitriptyline + nortriptyline, half-life and indications, actions, and dosage of, therapeutic and toxic levels of, 497 633t Amcil (ampicillin) Amlodipine (Norvasc), indications, indications, actions, and dosage actions, and dosage of, 496 of, 497 Ammonia, laboratory diagnosis and, 57 for subacute bacterial endocarditis Ammonium aluminum sulfate (Alum), prophylaxis, 158t, 159t indications, actions, and dosage of, Amcinonide (Cyclocort), potency and 496 application of, 628t Ammonium lactate [lactic acid + Amebiasis, drugs for treating, 153t ammonium hydroxide], Amenorrhea, differential diagnosis of, 42 indications, actions, and dosage of, Amerge (naratriptan), indications, actions, 558 and dosage of, 575–576 Amniotic fluid fern test, 242–243 Amicar (aminocaproic acid), indications, Amoxapine (Asendin), indications, actions, and dosage of, 494–495 actions, and dosage of, 496 Amifostine (Ethyol), indications, actions, Amoxicillin (Amoxil; Polymox) and dosage of, 494 indications, actions, and dosage Amikacin (Amikin) of, 496 half-life and therapeutic and toxic levels for subacute bacterial endocarditis of, 631t prophylaxis, 158t, 159t indications, actions, and dosage Amoxicillin + clavulanic acid of, 494 (Augmentin), indications, actions, Amiloride (Midamor), indications, and dosage of, 496 actions, and dosage of, 494 Amphojel (aluminum hydroxide) Amino acid solutions, for total parenteral for hyperphosphatemia, 192 nutrition, 229–230, 230t indications, actions, and dosage of, 493 Aminocaproic acid (Amicar), indications, Amphotec (amphotericin B cholesteryl), actions, and dosage of, 494–495 indications, actions, and dosage of, Amino-Cerv pH 5.5 Cream, indications, 497 actions, and dosage of, 495 Amphotericin B (Fungizone), indications, Aminoglutethimide (Cytadren), actions, and dosage of, 151t, indications, actions, and dosage of, 496–497 495 Amphotericin B cholesteryl (Amphotec), Aminoglycosides, 476 indications, actions, and dosage of, dosing procedure for, 620 497 levels of, 620, 631t Amphotericin B lipid complex (Abelcet), loading dose required for chosen dosing indications, actions, and dosage of, intervals for, 635t 497 Aminophylline, indications, actions, and Amphotericin B liposomal (Ambisome), dosage of, 495 indications, actions, and dosage of, Amiodarone (Cordarone; Pacerone) 497 for emergency cardiac care, 461 Ampicillin (Amcil; Omnipen) half-life and therapeutic and toxic levels indications, actions, and dosage of, 497 of, 632t for subacute bacterial endocarditis indications, actions, and dosage of, 495 prophylaxis, 158t, 159t Amitriptyline (Elavil) Ampicillin-sulbactam (Unasyn), indications, actions, and dosage of, 495 indications, actions, and dosage of, route, effects, and dosage for, 322t 497 664 Index Amprenavir (Agenerase), indications, indications, actions, and dosage of, 498 actions, and dosage of, 150t, 498 Ankle, arthrocentesis of, 249, 250f Amrinone (Inocor) Ankle-Arm Index (AAI), 266 for emergency cardiac care, 461 Ankle-brachial (A/B) index, 266 indications, actions, and dosage of, 498 Ann Arbor staging classification, 654 infusion guidelines for, 439t Anogenital warts, drugs of choice for Amylase, laboratory diagnosis and, 57 treating, 148t Amyl nitrate, for cyanide poisoning, 471 Anorexia, differential diagnosis of, 42 Analgesics Anoscopy, 300

for migraine headaches, 486 Ansaid (flurbiprofen), indications, actions, narcotic, 486 and dosage of, 541 nonnarcotic, 486 Antacids, 483 nonopioid, 320, 321t Anthralin (Anthraderm), indications, nonsteroidal anti-inflammatory agents, actions, and dosage of, 498 486 Antianxiety agents, 480 opioid, 320, 321t–322t Antiarrhythmic agents, 479 Anaphylaxis, 468–469 Antibiotics, 476–477 transfusions and, 203 antineoplastic, 478 Anaprox (naproxen), indications, actions, half-life and therapeutic and toxic levels and dosage of, 575 of, 631t Anaspaz (hyoscyamine), indications, ophthalmic, 483 actions, and dosage of, 551 Anticholinergic crisis, 469–470 Anastrozole (Arimidex), indications, Anticholinesterases, antidote for, 471 actions, and dosage of, 498 Anticoagulants, 484 Anatomic hand scrubs, 341 standards of practice for, 637t Ancef (cefazolin) Anticonvulsants, 480 indications, actions, and dosage of, 511 half-life and therapeutic and toxic levels for subacute bacterial endocarditis of, 631t–632t prophylaxis, 158t for pain management, 320 Ancylostoma duodenale infections, drugs Antidepressants, 480 for treating, 153t cyclic, antidote for, 471 Anectine (succinylcholine), indications, for pain management, 320 actions, and dosage of, 605 Antidiabetic agents, 482 Anemia, chronic, red blood cell Antidiarrheal agents, 483 transfusions for, 196 Antidiuretic hormone [vasopressin] Anergy screen (battery), 304 (Pitressin) Anestacon Topical. See Lidocaine indications, actions, and dosage (Anestacon Topical; Xylocaine) of, 617 Anesthetics infusion guidelines for, 443t local, 320, 348, 349t, 486 Antidotes, 471, 476 systemic, 320 Antiemetic agents, 483 Angiography, 327–328 Antifungals, 477 Angiotensin-converting enzyme (ACE) Antiglobulin test inhibitors, 479 direct, 105 for emergency cardiac care, 449 indirect, 105, 107 Angiotensin II receptor antagonists, 479 Antigout agents, 485 Anion gap, 166 Antihemophilic factor [AHF; factor VIII] Anion gap acidosis, 166 (Monoclate) Anistreplase (Eminase) indications, actions, and dosage of, 498 for emergency cardiac care, 467 for transfusion, 199t Index 665 Antihemophilic factor, cryoprecipitated, Apresoline (hydralazine), indications, 198t actions, and dosage of, 549 Antihistamines, 476 Aprotinin (Trasylol), indications, actions, Antilirium (physostigmine) and dosage of, 499 for anticholinergic crisis, 470 AquaMEPHYTON (phytonadione) antidote for, 471 indications, actions, and dosage of, 589 indications, actions, and dosage of, 589 in total parenteral nutrition, 231 Antimetabolites, 478 Ara-C [cytarabine] (Cytosar-U), Antimicrobial agents, 476–478. See also indications, actions, and dosage of, Antibiotics 522 Antimycobacterials, 477 Aramine (metaraminol), indications, Antineoplastic agents, 478–479 actions, and dosage of, 567 Antinuclear antibody (ANA; FANA), Arava (leflunomide), indications, actions, laboratory diagnosis and, 58 and dosage of, 559 Antiparkinson agents, 480 Ardeparin (Normiflo), indications, Antiplatelet agents, 484 actions, and dosage of, 499 Antipsychotics, 481 Arduan (pipecuronium), indications, Antiretrovirals, 477 actions, and dosage of, 590 Antistreptolysin O/antistreptococcal O Aredia (pamidronate) (ASO) titer, laboratory diagnosis for hypercalcemia, 189 and, 57 indications, actions, and dosage of, Antithrombic agents, 484 584–585 Antithrombin-III (AT-III), 105 Argyll-Robertson pupil, 21 Antithymocyte globulin [ATG] (Atgam), Arimidex (anastrozole), indications, indications, actions, and dosage of, actions, and dosage of, 498 499 Aristocort (triamcinolone acetonide), Antithyroid agents, 482 potency and application of, 630t Antitussives, 487 Artane (trihexyphenidyl), indications, Antiulcer agents, 483 actions, and dosage of, 614 Antivert (meclizine), indications, actions, Arterial line placement, 243–245, 244f and dosage of, 564 Arterial oxygen content (CaO2), derivation Antivirals, 477–478 and normal values for, 437t Anturane (sulfinpyrazone), indications, Arterial oxygen saturation (SAO ), for 2 actions, and dosage of, 606 cardiac output determination, 413 Anuria, differential diagnosis of, 43, Arterial puncture, 245–246 49–50 Arteriovenous oxygen (A-VO ) difference 2 Anusol Ointment (pramoxine), for cardiac output determination, indications, actions, and dosage of, 410–412, 411t 592 derivation and normal values for, Anzemet (dolasetron), indications, 437t actions, and dosage of, 529–530 Arthritis Aortic insufficiency (AI), 16t differential diagnosis of, 43 Aortic stenosis (AS), 16t septic, organisms responsible and AP films of chest, 325 empiric therapy for, 134t Apgar scores, 639, 640t synovial fluid interpretation and, 250 Apheresis, 194 Arthrocentesis, 246–250 Apley’s test, 21 contraindications to, 246 Apothecary measurement units, 646 indications for, 246 Apraclonidine (Iodipine), indications, materials for, 247 actions, and dosage of, 499 procedures for, 247–250, 248f–250f 666 Index Arthrocentesis (continued) Atenolol + chlorthalidone (Tenoretic), synovial fluid interpretation and, indications, actions, and dosage of, 249–250, 251t 500 Artificial tears (Tears Naturale), Atgam (antithymocyte globulin), indications, actions, and dosage of, indications, actions, and dosage of, 499 499 Asacol (mesalamine), indications, actions, Ativan (lorazepam) and dosage of, 566 indications, actions, and dosage of, 563 Ascariasis, drugs for treating, 153t for seizures, 472 Ascites, differential diagnosis of, 43 Atorvastatin (Lipitor), indications, actions, Ascitic fluid, diagnosis of, 297, 299t and dosage of, 500 Ascorbic acid, in total parenteral nutrition, Atovaquone (Mepron), indications, 231t actions, and dosage of, 500–501 Asendin (amoxapine), indications, actions, Atracurium (Tracrium), indications, and dosage of, 496 actions, and dosage of, 501 Aseptic meningitis, cerebrospinal fluid in, Atrial arrhythmias, on electrocardiograms, 287t 372–374, 373f–375f L-Asparaginase (Elspar), indica- Atrial fibrillation (AF), 373–374, 375f tions, actions, and dosage anticoagulant standard of practice for, of, 499 637t Aspartate aminotransferase (AST; SGOT), Atrial flutter, 374, 375f laboratory diagnosis and, 58 Atrial hypertrophy, electrocardiogram and, Aspergillosis, systemic drugs for treating, 380 151t Atrial septal defect (ASD), 17t Aspiration, with enteral nutrition, 223 Atrioventricular junctional or nodal Aspirin (sodium salicylate) rhythm, 374–375, 376f for emergency cardiac care, 461 Atrophy, of skin, 20 indications, actions, and dosage of, Atropine, 364 499–500 for anticholinesterase poisoning, 471 route, effects, and dosage for, 321t indications, actions, and dosage of, 501 Aspirin + butalbital, caffeine and codeine Atropine sulfate, for emergency cardiac (Fiorinal + Codeine), indications, care, 461 actions, and dosage of, 500 Attending physicians, 2 Aspirin + butalbital compound (Fiorinal; Attending rounds, 3 Lanorinal), indications, actions, Auer rods, 104 and dosage of, 500 Aufalglan (benzocaine + antipyrine), Aspirin + codeine (Empirin No. 2, No. 3, indications, actions, and dosage of, No. 4), indications, actions, and 504 dosage of, 500 Augmentin (amoxicillin + clavulanic Assist controlled ventilation, 424, 425f acid), indications, actions, and Asthmatic attacks, 469 dosage of, 496 Asystole algorithm, 454f Austin Flint murmur, 21 Atacand (candesartan), indications, Autoantibodies, laboratory diagnosis and, actions, and dosage of, 509 58 Atarax (hydroxyzine), indications, actions, Autoantibody test, 105, 107 and dosage of, 551 Autologous blood donation, 193–194 Atenolol (Tenormin) Avandia (rosiglitazone), indications, for emergency cardiac care, 462 actions, and dosage of, 599–600 indications, actions, and dosage Avapro (irbesartan), indications, actions, of, 500 and dosage of, 555 Index 667 Avelox (moxifloxacin), indications, Bacillus fragilis, Gram stain actions, and dosage of, 574 characteristics of, 126t Aventyl (nortriptyline) Bacitracin half-life and therapeutic and toxic levels neomycin, polymyxin B, + of, 633t hydrocortisone, ophthalmic (AK indications, actions, and dosage of, 580 Spore HC Ophthalmic; Cortisporin Avita (tretinoin, topical), indications, Ophthalmic), indications, actions, actions, and dosage of, 613 and dosage of, 502 Avlosulfon (dapsone), indications, actions, neomycin, polymyxin B, + and dosage of, 523 hydrocortisone, topical (Cortisporin), Avulsed teeth, 470 indications, actions, and dosage of, Axid (nizatidine), indications, actions, and 502 dosage of, 579 neomycin, polymyxin B, + lidocaine, Axis deviation, o electrocardiograms, topical (Clomycin), indications, 369–370, 370f actions, and dosage of, 502 Azactam (aztreonam), indications, actions, neomycin, + polymyxin B, ophthalmic and dosage of, 501 (AK Spore Ophthalmic; Neosporin Azathioprine (Imuran), indications, Ophthalmic), indications, actions, actions, and dosage of, 501 and dosage of, 502 Azithromycin (Zithromax) neomycin, + polymyxin B, topical indications, actions, and dosage of, 501 (Neosporin ointment), indications, for subacute bacterial endocarditis actions, and dosage of, 502 prophylaxis, 158t Bacitracin, ophthalmic (AK-Tracin Azopt (brinzolamide), indications, actions, Ophthalmic), indications, actions, and dosage of, 506 and dosage of, 502 Azotemia, progressive, 432–433 Bacitracin + polymyxin B, ophthalmic Aztreonam (Azactam), indications, (AK Poly Bac Ophthalmic; actions, and dosage of, 501 Polysporin Ophthalmic), Azulfidine (sulfasalazine), indications, indications, actions, and dosage of, actions, and dosage of, 605–606 502 Bacitracin + polymyxin B, topical (Polysporin), indications, actions, B and dosage of, 502 Babesia microti infections, characteristics Bacitracin, topical (Baciguent), and treatment of, 156t–157t indications, actions, and dosage of, Babesiosis, characteristics and treatment 502 of, 156t–157t Back pain, differential diagnosis of, 43 Babinski’s sign, 24 Baclofen (Lioresal), indications, actions, Baby bilirubin, laboratory diagnosis and, and dosage of, 502 59 Bacterial endocarditis Baciguent (bacitracin, topical), organisms responsible and empiric indications, actions, and dosage of, therapy for, 136t–137t 502 subacute, prophylaxis, 155, 158t–159t Bacilli anthracis, Gram stain Bacterial infections. See also specific characteristics of, 125t infections Bacillus, Gram stain characteristics of, cerebrospinal fluid in, 287t 123f transfusion-associated risk of Bacillus Calmette-Guérin [BCG], transmission, 204 indications, actions, and dosage of, Bactocill (oxacillin), indications, actions, 503 and dosage of, 582–583 668 Index Bactrim (trimethoprim-sulfamethoxazole), for anaphylaxis, 469 indications, actions, and dosage of, indications, actions, and dosage of, 528 153t, 615 Benazepril (Lotensin), indications, Bactroban (mupirocin), indications, actions, and dosage of, 503 actions, and dosage of, 574 Benemid (probenecid), indications, Bainbridge’s reflex, 24 actions, and dosage of, 593 Baker tubes, 273 Benign prostatic hyperplasia, medications Balloon port, of Swan-Ganz catheter, 399 for, 487 Band cells, 100 Bentyl (dicyclomine), indications, actions, Barium enema (BE), 328 and dosage of, 526 Barium swallow, 328 Benylin DM (dextromethorphan), Basal energy expenditure (BEE), 209 indications, actions, and dosage of, Basaljel (aluminum carbonate) 525 for hyperphosphatemia, 192 Benzamycin (erythromycin + benzoyl indications, actions, and dosage of, 493 peroxide), indications, actions, and Base excess/deficit, laboratory diagnosis dosage of, 534 and, 59 Benznidazole, indications for, 154t Basiliximab (Simulect), indications, Benzocaine + antipyrine (Aufalglan), actions, and dosage of, 502 indications, actions, and dosage of, Basophil(s), laboratory diagnosis and, 101 504 Basophilia, 100, 104 Benzonatate (Cogentin), indications, Basophilic stippling, 104 actions, and dosage of, 504 Battle’s sign, 24 Bepridil (Vascar), indications, actions, and Baycol (cerivastatin), indications, actions, dosage of, 504 and dosage of, 514 Beractant (Survanta), indications, actions, BCG [bacillus Calmette-Guérin] (BCG; and dosage of, 504 Thera Cys; TICE), indica- Bergman’s triad, 24 tions, actions, and dosage Beta blockers, 479–480 of, 503 antidote for, 471 BCNU (carmustine), indications, actions, for emergency cardiac care, 461–462 and dosage of, 510 Betadine hand scrub, 340–341 Beat-to-beat variability, 276 Betagan (levobunolol), indications, Beau’s lines, 24 actions, and dosage of, 560 Becaplermin (Regranex Gel), indications, Betamethasone, dose, activity, duration, actions, and dosage of, 503 and route for, 627t Beck’s triad, 24 Betamethasone dipropionate (Diprosone), Beclomethasone (Beconase; Vancenase potency and application of, 628t Nasal Inhaler), indications, Betamethasone valerate (Valisone), actions, and dosage of, 503 potency and application of, 628t Bedside procedures, 239–314. See also Betapace (sotalol), indications, actions, specific procedures and dosage of, 602 basic equipment for, 240, 240t, 241f, Beta-1 receptors, 397 242f Beta-2 receptors, 397 notes for, 35 Betaseron (interferon ß-1B), indications, Bedside rounds, 4 actions, and dosage of, 554 Belladonna + opium suppositories (B & O Betaxolol (Kerlone), indications, actions, Supprettes), indications, actions, and dosage of, 504 and dosage of, 503 Betaxolol, ophthalmic (Betoptic), Bell’s palsy, 24 indications, actions, and dosage of, Benadryl (diphenhydramine) 504 Index 669 Bethanechol (Duvoid; Urecholine), indications for, 306 indications, actions, and dosage of, materials for, 307, 307f 504–505 procedure for, 307–308 Betoptic (betaxolol, ophthalmic), Blastomycosis, systemic drugs for indications, actions, and dosage of, treating, 151t 504 Bleeding scans, 333 Biaxin (clarithromycin) Bleeding time, 105 indications, actions, and dosage of, 517 Bleomycin sulfate (Blenoxane), for subacute bacterial endocarditis indications, actions, and dosage of, prophylaxis, 158t 505–506 Bicalutamide (Casodex), indications, Bleph-10 (sulfacetamide), indications, actions, and dosage of, 505 actions, and dosage of, 605 Bicarbonate. See also Potassium Blephamide (sulfacetamide + bicarbonate; Sodium bicarbonate prednisolone), indications, actions, laboratory diagnosis and, 59, 61–62 and dosage of, 605 Bicillin (penicillin G benzathine), Blocadren (timolol), indications, actions, indications, actions, and dosage of, and dosage of, 610 586 Blood, in urine, 111 Bicitra (sodium citrate), indications, Blood alcohol, laboratory diagnosis and, actions, and dosage of, 602 67 BiCNU (carmustine), indications, actions, Blood and body fluid precautions, 155 and dosage of, 510 Blood collection, 95 BIDA-scans, 334 heelstick for, 274, 275f Bigeminy, 375, 377f venipuncture for, 309–314 Bile loss, IV fluid replacement with, 179 Blood component therapy, 193–204 Bilirubin apheresis for, 194 neonatal, laboratory diagnosis and, 59 autologous blood donation for, 193–194 in urine, 111 blood banking procedures, 193 Biopsy, of skin, 302 blood groups and, 194, 196t Biotin, in total parenteral nutrition, 231t donor-restricted blood products for, 194 Biot’s breathing, 24 emergency transfusions, 194 Bisacodyl (Dulcolax), indications, actions, infectious disease risk associated with, and dosage of, 505 203–204 Bisferious pulse, 24 irradiated blood components for, 194 Bismuth subsalicylate (Pepto-Bismol), preoperative blood set up for, 194, 195t indications, actions, and dosage of, procedure for, 201–202 505 products for, 196, 197t–200t, 201 Bisoprolol (Zebeta), indications, actions, routine blood donation for, 193 and dosage of, 505 transfusion reactions and, 202–203 Bite wound (human and animal) Blood cultures, 129–130 infections, organisms responsible Blood gases, 161–163 and empiric therapy for, 142t capillary, 161 Bitolterol (Tornalate), indications, actions, determination of, 162–163 and dosage of, 505 interpretation of, 163, 165–166 Bitot’s spots, 24 normal values for, 161, 162t Bladder

aspiration, suprapubic, venous, 161 percutaneous, 309, 310f Blood groups, 194, 196t Bladder cancer, staging of, 650–651 Blood loss Bladder catheterization, 306–308 acute, red blood cell transfusions for, contraindications to, 306 196 670 Index Blood loss (continued) Bretylium allowable, red blood cell transfusions indications, actions, and dosage for, 196 of, 506 Blood pressure guidelines, 14, 20t infusion guidelines for, 439t Blood pressure measurement, of Brevibloc (esmolol) orthostatic pressure, 286–289 for emergency cardiac care, 462 Blood smears, 95–97, 96f, 97t indications, actions, and dosage Blood urea nitrogen (BUN), laboratory of, 534 diagnosis and, 59 infusion guidelines for, 440t Blood volume, total, 177 Brevicon 21, 28, 623t Blumberg’s sign, 24 Bricanyl (terbutaline), indications, actions, Blumer’s shelf, 24 and dosage of, 608 Body fluids. See also Fluids and Brimonidine (Alphagan), indications, electrolytes; specific fluids and actions, and dosage of, 506 electrolytes Brinzolamide (Azopt), indications, composition and daily production of, actions, and dosage of, 506 181t Broad casts, in urine sediment, 114 total body water, 177 Bromocriptine (Parlodel), indications, Body surface area actions, and dosage of, 506 of adults, 639, 641f Bronchiolitis, drug of choice for treating, of children, 639, 642f 148t Body weight, desirable, 639, 640t Bronchitis, organisms responsible and Bone infections, organisms responsible empiric therapy for, 134t and empiric therapy for, 134t Bronchodilators, 487 Bone marrow aspiration/biopsy, 250, half-life and therapeutic and toxic levels 252–253 of, 632t Bone scans, 333 Bronchopulmonary hygiene, 362–364 Bone turnover, high, hypercalcemia with, Brontex (guaifenesin + codeine), 188 indications, actions, and dosage of, Bordetella pertussis, Gram stain 546 characteristics of, 124f, 126t Brucella, Gram stain characteristics of, Borrelia burgdorferi infections, 124f, 126t characteristics and treatment of, Brudzinski’s sign, 24 156t–157t Brugia malayi infections, drugs for B & O Supprettes (belladonna + opium treating, 153t suppositories), indications, actions, Buclizine (Bucladin-s Softabs), and dosage of, 503 indications, actions, and dosage of, Bouchard’s nodes, 24 506 Bradycardia, 276, 371 Budesonide (Pulmicort; Rhinocort), algorithm for, 455f indications, actions, and dosage of, Brain scans, 333 506 Branhamella catarrhalis, Gram stain Bullae, 20 characteristics of, 125t Bumetanide (Bumex), indications, actions, Branham’s sign, 24 and dosage of, 506–507 Breast cancer Buminate (albumin), indications, actions, screening recommendations for, 643t and dosage of, 200t, 490 staging of, 649–650 BUN/creatinine ratio (BUN/CR), Breast lumps, differential diagnosis of, 43 laboratory diagnosis and, 59–60 Brethine (terbutaline), indications, actions, Bundle branch block (BBB), 379, 380f, and dosage of, 608 381f Index 671 Bupivacaine (Marcaine; Sensoricaine) Calcium acetate (Calphron; Phos-Ex; indications, actions, and dosage of, 507 PhosLo), indications, actions, and for suturing, 349t dosage of, 508 Buprenorphine (Buprenex), indications, Calcium alginate swab, 129 actions, and dosage of, 507 Calcium carbonate (Alka-Mints; Tums) Bupropion (Wellbutrin; Zyban), for hypocalcemia, 190 indications, actions, and dosage of, indications, actions, and dosage of, 508 507 Calcium-channel blockers, 479 Burn wounds antidote for, 471 infections of, organisms responsible and Calcium chloride empiric therapy for, 141t–142t for calcium-channel blocker poisoning, IV fluid replacement with, 179 471 Burr cells, 104 for emergency cardiac care, 462 Burrows, 20 for hyperkalemia, 187 Buspirone (Buspar), indications, actions, for hypocalcemia, 190 and dosage of, 507 indications, actions, and dosage of, Busulfan (Myleran), indications, actions, 508–509 and dosage of, 507 Calcium citrate, for hypocalcemia, 190 Butorphanol (Stadol), indications, actions, Calcium glubionate (Neo-calglucon) and dosage of, 507 for hypocalcemia, 190 Butterfly needles, 280 indications, actions, and dosage of, 508 Calcium gluceptate, indications, actions, and dosage of, 508–509 C Calcium gluconate C. diphtheriae, throat culture for, 131 for emergency cardiac care, 462 CA 15-3, laboratory diagnosis and, 60 for hypermagnesemia, 190 CA 19-9, laboratory diagnosis and, 60 for hypocalcemia, 190 CA-125, laboratory diagnosis and, 60 indications, actions, and dosage of, Caffeine, half-life and therapeutic and 508–509 toxic levels of, 632t Calcium lactate, for hypocalcemia, 190 Calan (verapamil) Calcium salts (chloride, gluconate, for emergency cardiac care, 467 gluceptate), indications, actions, indications, actions, and dosage and dosage of, 508–509 of, 617 CaldeCort (hydrocortisone) Calcipotriene (Davonex), indications, indications, actions, and dosage actions, and dosage of, 507–508 of, 550 Calcitonin, blood levels of, laboratory potency and application of, 629t diagnosis and, 61 Calfactant (Infasurf), indications, actions, Calcitonin (Cibocalcin; Miacalcin) and dosage of, 509 for hypercalcemia, 189 Calgiswab, 129 indications, actions, and dosage Caloric requirements of, 508 calculation of, 209, 213 Calcitriol (Rocaltrol), indications, actions, in stressed patients, calculation and dosage of, 508 of, 228 Calcium Calphron (calcium acetate), indications, elemental, for hypocalcemia, 190 actions, and dosage of, 508 excess of. See Hypercalcemia Camptosar (irinotecan), indications, requirement for, 178 actions, and dosage of, 555 serum, laboratory diagnosis and, 61 Cancer urine, 116 hypercalcemia with, 188 672 Index Cancer (continued) algorithms for, 450f–460f screening recommendations for, 639, drugs used in, 449, 461–467 643t–644t electrical defibrillation and Cancer-related check-ups, 644t cardioversion for, 467–468 Candesartan (Atacand), indications, Cardiac contractility, 395 actions, and dosage of, 509 measurement of, 410 Candidiasis Cardiac failure, renal failure, 235 cystitis due to, systemic drugs for Cardiac hypertrophy, on treating, 151t electrocardiograms, 380–383, oral, systemic drugs for treating, 151t 381f–383f vaginal. See Vaginal candidiasis Cardiac index (CI), 395 Cantor tubes, 272 derivation and normal values for, 437t Capillary fingersticks/heelsticks, 95 Cardiac output (CO), 395 Capoten (captopril) adrenergic nervous system and, 395, for emergency cardiac care, 449 397, 397t, 398t indications, actions, and dosage of, 509 derivation and normal values for, 437t Capsaicin (Capsin; Zostrix), indications, determinants of, 395, 396f actions, and dosage of, 509 determinations of, 410–413 Captopril (Capoten) Cardiac pacing, 468 for emergency cardiac care, 449 Cardiac scans, 333–334 indications, actions, and dosage of, 509 Cardiogenic shock, 414, 431 Captopril test, 61 Cardiomyopathy, anticoagulant standard Caraway tubes, 274 of practice for, 637t Carbamazepine (Tegretol) Cardiopulmonary resuscitation (CPR), half-life and therapeutic and toxic levels 445–449 of, 631t adult, 445–447, 448 indications, actions, and dosage of, 509 child, 447, 448 route, effects, and dosage for, 322t foreign body obstructed airway Carbidopa + levodopa (Sinemet), sequence for, 448 indications, actions, and dosage of, infant, 447, 448 509–510 neonatal, 447–448 Carbocaine (mepivacaine), for suturing, one-rescuer, 445–446 349t primary survey for, 447 Carbohydrate controlled diet, 207t recovery position for, 449 Carbon dioxide, laboratory diagnosis and, secondary survey for, 447 61–62 two-rescuer, 446–447 Carbon monoxide Cardiovascular agents, 479–480 antidote for, 471 half-life and therapeutic and toxic levels laboratory diagnosis and, 62 of, 632t–633t Carboplatin (Paraplatin), indications, Cardiovascular evaluation, 391–395 actions, and dosage of, 510 blood pressure in, 392–393 Carboxyhemoglobin, laboratory diagnosis heart murmurs in, 393–395 and, 62 inspection in, 391–392 Carcinoembryonic antigen (CEA), mean arterial blood pressure in, 393, laboratory diagnosis and, 62 394f Cardene (nicardipine) pulse pressure in, 393 indications, actions, and dosage of, 578 Cardioversion, 468 infusion guidelines for, 441t–442t DC-synchronized, 374 Cardiac angiography, 328 Cardizem (diltiazem) Cardiac care, emergency, 449–468 for emergency cardiac care, 462 Index 673 indications, actions, and dosage of, 528 Cefaclor (Ceclor), indications, actions, infusion guidelines for, 439t and dosage of, 510–511 Cardura (doxazosin), indications, actions, Cefadroxil (Duricef; Ultracef) and dosage of, 530 indications, actions, and dosage of, 511 Carisoprodol (Soma), indications, actions, for subacute bacterial endocarditis and dosage of, 510 prophylaxis, 158t Carmustine (BCNU; BiCNU), indications, Cefadyl (cephapirin), indications, actions, actions, and dosage of, 510 and dosage of, 514 Carteolol (Cartrol; Occupress Cefazolin (Ancef; Kefzol) Ophthalmic), indications, actions, indications, actions, and dosage and dosage of, 510 of, 511 Carvedilol (Coreg), indications, actions, for subacute bacterial endocarditis and dosage of, 510 prophylaxis, 158t Casodex (bicalutamide), indications, Cefdinir (Omnicef), indications, actions, actions, and dosage of, 505 and dosage of, 511 Casts, in urine sediment, 114 Cefepime (Maxipime), indications, Cataflam (diclofenac) actions, and dosage of, 511 indications, actions, and dosage of, 526 Cefixime (Suprax), indications, actions, route, effects, and dosage for, 321t and dosage of, 511 Catapres (clonidine, oral), indications, Cefizox (ceftizoxime), indications, actions, and dosage of, 518 actions, and dosage of, 513 Catapres TS (clonidine, transdermal), Cefmetazole (Zefazone), indications, indications, actions, and dosage of, actions, and dosage of, 511 518 Cefobid (cefoperazone), indications, Catecholamines actions, and dosage of, 512 fractional serum, laboratory diagnosis Cefonicid (Monocid), indications, actions, and, 62 and dosage of, 511–512 fractionated, in urine, 117 Cefoperazone (Cefobid), indications, Cathartics, 483 actions, and dosage of, 512 Catheter(s). See also Bladder Cefotan (cefotetan), indications, actions, catheterization; Central venous and dosage of, 512 catheterization; Peripherally Cefotaxime (Claforan), indications, inserted central catheter (PICC) actions, and dosage of, 512 lines; Pulmonary artery catheters Cefotetan (Cefotan), indications, actions, French units for, 240, 241f and dosage of, 512 vascular, sepsis of, 435 Cefoxitin (Mefoxin), indications, actions, Catheterization. See Peripherally inserted and dosage of, 512 central catheter (PICC) lines Cefpodoxime (Vantin), indications, Caverject (alprostadil, intracavernosal), actions, and dosage of, 512 indications, actions, and dosage of, Cefprozil (Cefzil), indications, actions, 492 and dosage of, 512 Cavitary lesions, of lungs, 338 Ceftazidime (Ceptaz; Fortaz; Tazicef; CCNU (lomustine), indications, actions, Tazidime), indications, actions, and dosage of, 562 and dosage of, 513 Ceclor (cefaclor), indications, actions, and Ceftibutin (Cedax), indications, actions, dosage of, 510–511 and dosage of, 513 Cedax (ceftibutin), indications, actions, Ceftin (cefuroxime), indications, actions, and dosage of, 513 and dosage of, 513 CeeNu (lomustine), indications, actions, Ceftizoxime (Cefizox), indications, and dosage of, 562 actions, and dosage of, 513 674 Index Ceftriaxone (Rocephin), indications, Cephulac (lactulose), indications, actions, actions, and dosage of, 513 and dosage of, 558 Cefuroxime (Ceftin; Zinacef), indications, Ceptaz (ceftazidime), indications, actions, actions, and dosage of, 513 and dosage of, 513 Cefzil (cefprozil), indications, actions, and Cerebellum, herniation of, with lumbar dosage of, 512 puncture, 286 Celecoxib (Celebrex) Cerebral angiography, 328 indications, actions, and dosage of, 513 Cerebral perfusion pressure (CPP), route, effects, and dosage for, 321t derivation and normal values for, Celexa (citalopram), indications, actions, 438t and dosage of, 517 Cerebrospinal fluid (CSF), differential Cellcept (mycophenolate mofetil), diagnosis of, 287t–288t indications, actions, and dosage of, Cerebryx (fosphenytoin) 574 indications, actions, and dosage of, 543 Cellulitis, organisms responsible and for seizures, 473t empiric therapy for, 142t Cerivastatin (Baycol), indications, actions, Celsius/Fahrenheit conversion, 646, 649t and dosage of, 514 Cenestin (estrogens, conjugated- Cerubidine (daunorubicin), indications, synthetic), indications, actions, and actions, and dosage of, 523 dosage of, 535–536 Cerumenex (triethanolamine), indications, Centrally acting antihypertensive agents, actions, and dosage of, 614 479 Cervical cancer Central nervous system agents, 480–481 screening recommendations for, 643t Central venous catheterization, 253–260 staging of, 651–652 catheter removal and, 260 Cervical infections, tests for, 291 complications of, 257–258, 260 Cervicitis, organisms responsible and contraindications to, 254 empiric therapy for, 135t femoral vein approach for, 259–260 Cetamide (sulfacetamide), indications, historical background of, 254 actions, and dosage of, 605 indications for, 253 Cetirizine (Zyrtec), indications, actions, left internal jugular vein approach for, and dosage of, 514 258–259, 259f Chadwick’s sing, 24 materials for, 254 Chagas’ disease, drugs for treating, 154t right internal jugular vein approach for, Chancroid, organism responsible and 256–258, 257f empiric therapy for, 135t subclavian approach for, 254–256 Chandelier sign, 24, 290 Central venous pressure (CVP), 397–399, Charcot’s triad, 24 398t Chartwork, 33–40 derivation and normal values for, 437t Check-out rounds, 3–4 Centrax (prazepam), indications, actions, Chemet (succimer), indications, actions, and dosage of, 593 and dosage of, 604–605 Cephalexin (Keflex; Keftab) Chemically defined formulas, for enteral indications, actions, and dosage of, 513 nutrition, 217 for subacute bacterial endocarditis Chest computed tomography, 331 prophylaxis, 158t Chest electrodes, 267, 267f Cephalosporins, 476 Chest magnetic resonance imaging, 332 Cephapirin (Cefadyl), indications, actions, Chest pain, differential diagnosis of, 43 and dosage of, 514 Chest physiotherapy, 363 Cephradine (Velosef), indications, actions, Chest tube placement, 260–263 and dosage of, 514 complications of, 263 Index 675 historical background of, 261 Cholangiography, T-tube, 329 indications for, 260–261 Cholangitis, organisms responsible and materials for, 261 empiric therapy for, 137t procedure for, 261–263, 262f Cholecalciferol [vitamin D3], Chest x-rays, 325 indications, actions, and dosage reading, 335, 336f, 337f, 338 of, 516 Cheyne-Stokes respirations, 24 Cholecystitis Children. See also Infant formulas and acalculous, 434 feeding organisms responsible and empiric body surface area of, 639, 642f therapy for, 137t “rule of sixes” nomogram for Cholestasis, total parenteral nutrition for, calculating fluids in, 179, 181t 237 Chills, differential diagnosis of, 43 Cholesterol, laboratory diagnosis and, Chlamydia cultures, 291 62–63, 63t, 80f Chlamydial infections, organism Cholesterol restricted diet, 208t responsible and empiric therapy Cholestyramine (Questran), indications, for, 135t actions, and dosage of, 516 Chloral hydrate (Noctec), indications, Chromic catgut sutures, 346t actions, and dosage of, 514 Chromium, in total parenteral nutrition, Chlorambucil (Leukeran), indications, 231, 232t actions, and dosage of, 514 Chronulac (lactulose), indications, actions, Chlordiazepoxide (Librium), indications, and dosage of, 558 actions, and dosage of, 515 Chvostek’s sign, 24 Chlorhexidine 6-min hand scrub, 341 Chylothorax, 50 Chloride Cibocalcin (calcitonin) requirement for, 178 for hypercalcemia, 189 serum, laboratory

diagnosis and, 62 indications, actions, and dosage spot urine study for, 114 of, 508 Chloride-insensitive (resistant) metabolic Ciclopirox (Loprox), indications, actions, alkalosis, 169 and dosage of, 516 Chloride-sensitive (responsive) metabolic Cidofovir (Vistide), indications, actions, alkalosis, 167, 169 and dosage of, 146t, 516 Chloroquine phosphate, indications for, 153t Ciloxan (ciprofloxacin, ophthalmic), Chlorothiazide (Diuril), indications, indications, actions, and dosage of, actions, and dosage of, 515 517 Chlorpheniramine (Chlor-Trimeton), Cimetidine (Tagamet), indications, indications, actions, and dosage of, actions, and dosage of, 516 515 Ciprofloxacin (Cipro), indications, Chlorpromazine (Thorazine), indications, actions, and dosage of, 516 actions, and dosage of, 515 Ciprofloxacin, ophthalmic (Ciloxan), Chlorpropamide (Diabinese), indications, indications, actions, and dosage of, actions, and dosage of, 515 517 Chlorthalidone (Hygroton), indications, Ciprofloxacin, otic (Cipro HC Otic), actions, and dosage of, 515 indications, actions, and dosage of, Chlor-Trimeton (chlorpheniramine), 517 indications, actions, and dosage of, Cipro HC Otic (ciprofloxacin, otic), 515 indications, actions, and dosage of, Chlorzoxazone (Paraflex; Parafon Forte 517 DSC), indications, actions, and Cisplatin (Platinol AQ), indications, dosage of, 515–516 actions, and dosage of, 517 676 Index 13-cis retinoic acid [isotretinoin] Clopra (metoclopramide), indications, (Accutane), indications, actions, actions, and dosage of, 569 and dosage of, 555–556 Clorazepate (Tranxene), indications, Citalopram (Celexa), indications, actions, actions, and dosage of, 519 and dosage of, 517 Clostridium, Gram stain characteristics of, Citrobacter, Gram stain characteristics of, 123f, 126t 124f Clostridium difficile assay, 63, 131 Cladribine (Leustatin), indications, Clotrimazole (Lotrimin; Mycelex), actions, and dosage of, 517 indications, actions, and dosage of, Claforan (cefotaxime), indications, 519 actions, and dosage of, 512 Clotrimazole + betamethasone Clarithromycin (Biaxin) (Lotrisone), indications, actions, indications, actions, and dosage and dosage of, 519 of, 517 Cloxacillin (Cloxapen; Tegopen), for subacute bacterial endocarditis indications, actions, and dosage of, prophylaxis, 158t 519 Claritin (loratadine), indications, actions, Clozapine (Clozaril), indications, actions, and dosage of, 563 and dosage of, 519 Clean catch urine specimens, urine, Clubbing, differential diagnosis of, 43 308–309 Coagulation cascade, 106f Clear liquid diet, 206t–207t Cocaine, indications, actions, and dosage Clemastine fumarate (Tavist), indications, of, 519–520 actions, and dosage of, 518 Coccidioidomycosis, systemic drugs for Clindamycin (Cleocin; Cleocin-T) treating, 151t indications, actions, and dosage of, Codeine 153t, 518 indications, actions, and dosage of, for subacute bacterial endocarditis 520 prophylaxis, 158t route, effects, and dosage for, 321t Clinoril (ulindac), indications, actions, and Cogentin (benzonatate), indications, dosage of, 606 actions, and dosage of, 504 Clobetasol propionate (Temovate), Cognex (tacrine), indications, actions, and potency and application dosage of, 606 of, 628t Coin lesions, of lungs, 338 Clocortolone pivalate (Cloderm), potency Colace (docusate sodium), indications, and application of, 628t actions, and dosage of, 529 Clofazimine (Lamprene), indications, Colchicine, indications, actions, and actions, and dosage of, 518 dosage of, 520 Clomycin (bacitracin, neomycin, Cold agglutinins, laboratory diagnosis polymyxin B, + lidocaine, topical), and, 63–64 indications, actions, and dosage of, Colesevelam (Welchol), indications, 502 actions, and dosage of, 520 Clonazepam (Klonopin), indications, Colestid (colestipol), indications, actions, actions, and dosage of, 518 and dosage of, 520 Clonidine, oral (Catapres), indications, Colfosceril palmitate (Exosurf Neonatal), actions, and dosage of, 518 indications, actions, and dosage of, Clonidine, transdermal (Catapres TS), 520 indications, actions, and dosage of, Colitis, cytomegalovirus, drugs of choice 518 for treating, 146t Clopidogrel (Plavix), indications, actions, Colloids, composition of, 178 and dosage of, 519 Color, of urine, 110 Index 677 Colorectal cancer Coombs’ test screening recommendations for, 643t direct, 105 staging of, 652 indirect, 105, 107 CoLyte (polyethylene glycol [PEG]- Copper, in total parenteral nutrition, 231, electrolyte solution), indications, 232t actions, and dosage of, 590–591 Cordarone (amiodarone) Coma, 470 for emergency cardiac care, 461 differential diagnosis of, 44 half-life and therapeutic and toxic levels Combivent (albuterol + ipratropium), of, 632t indications, actions, and dosage of, indications, actions, and dosage of, 495 490 Cordran (flurandrenolide), potency and Combivir (zidovudine + lamivudine), application of, 629t indications, actions, and dosage of, Coreg (carvedilol), indications, actions, 619 and dosage of, 510 Compazine (prochlorperazine), indica- Corgard (nadolol), indications, actions, tions, actions, and dosage of, 594 and dosage of, 574 Complement, laboratory diagnosis and, 64 Corlopam (fenoldopam), indications, Complete blood cell count (CBC) actions, and dosage of, 537 left shift in, 100 Corrected reticulocyte count, 100–101 normal values for, 97, 98t–99t Corrigan’s pulse, 24 normal variations in, 97 Corticaine (hydrocortisone acetate) Computed tomography (CT), 330–331 indications, actions, and dosage Comtan (entacapone), indications, actions, of, 603 and dosage of, 532 potency and application of, 629t Comvax (haemophilus B conjugate Corticosteroids. See also specific vaccine), indications, actions, and corticosteroids dosage of, 547 for hypercalcemia, 189 Condylox (podophyllin), indications, for pain management, 320 actions, and dosage of, 148t, in urine, 118 590–591 Cortisol Condylox Gel 0.5% (podophyllin), free, in urine, 117 indications, actions, and dosage of, serum, laboratory diagnosis and, 64 148t, 590–591 Cortisone (Cortone) Conjunctivitis, organism responsible and dose, activity, duration, and route for, empiric therapy for, 135t 627t Consent, informed, 240 indications, actions, and dosage Constipation of, 603 differential diagnosis of, 44 Cortisporin (bacitracin, neomycin, with enteral nutrition, 223 polymyxin B, + hydrocortisone, Contact isolation, 155 topical), indications, actions, and Contaminants, in urine sediment, 112 dosage of, 502 Continuous positive airway pressure Cortisporin Ophthalmic (bacitracin, (CPAP), 426 neomycin, polymyxin B, + Contrast media, 327 hydrocortisone, ophthalmic), reactions to, 327 indications, actions, and dosage of, Controlled substances, 475–476 502 Controlled ventilation, 424, 425f Cortisporin Ophthalmic and Otic Conus medullaris trauma, with lumbar (neomycin, polymyxin, + puncture, 286 hydrocortisone), indications, Convalescent specimens (titers), 132 actions, and dosage of, 577 678 Index Cortisporin-TC Otic Drops (neomycin, serum, laboratory diagnosis and, 65 colistin, + hydrocortisone), Creatinine clearance, 115–116 indications, actions, and dosage of, determination of, 116 576 Creatinine phosphokinase (CPK) Cortisporin-TC Otic Suspension isoenzymes of, laboratory diagnosis (neomycin, colistin, and, 65 hydrocortisone, + thonzonium), laboratory diagnosis and, 65 indications, actions, and dosage of, Creeping eruption, drugs for treating, 576 153t Cortizone (hydrocortisone) Creon (pancreatin + pancrelipase), indications, actions, and dosage of, 550 indications, actions, and dosage of, potency and application of, 629t 585 Cortone (cortisone) Cricothyrotomy, 263–264 dose, activity, duration, and route for, Critical care. See Intensive care unit (ICU) 627t Critical closing volume (CCV), 416f, 417 indications, actions, and dosage of, 603 Critical illness, hypocalcemia and, 189 Cortrosyn stimulation test, 55–56 Crixivan (indinavir), indications, actions, Corvert (ibutilide) and dosage of, 150t, 553 for emergency cardiac care, 464 Cromolyn sodium (Intal; Nasalcrom; indications, actions, and dosage of, 551 Opticrom), indications, actions, Corynebacterium, Gram stain and dosage of, 520–521 characteristics of, 123f, 126t Cross-table lateral abdominal x-rays, 326 Cosmegen (dactinomycin), indications, Crotamiton, indications for, 154t actions, and dosage of, 523 Croup, 131 Cosopt (dorzolamide + timolol), Crusts, 20 indications, actions, and dosage of, Cryocrit, laboratory diagnosis and, 65 530 Cryoglobulins, laboratory diagnosis and, Cotazyme (pancreatin + pancrelipase), 65 indications, actions, and dosage of, Cryoprecipitated antihemophilic factor, 585 198t Co-trimoxazole [trimethoprim- Cryptococcosis, systemic drugs for sulfamethoxazole] (Bactrim; treating, 151t Septra), indications, actions, and Cryptosporidiosis, drugs for treating, 153t dosage of, 153t, 615 Crystal(s), in urine sediment, 112 Coudé catheter, 307, 307f Crystalline amino acid solutions, for total Cough, differential diagnosis of, 44 parenteral nutrition, 229–230, Coumadin (warfarin) 230t indications, actions, and dosage Crystalloids, composition of, 180t of, 618 Crystal violet, 122 interaction with enteral nutrition, 223 C-spine x-rays, 326 Counterimmunoelectrophoresis (CEP; Culdocentesis, 264–265 CIEP), laboratory diagnosis and, Cullen’s sign, 24 64–65 Curling’s ulcers, 433 Cozaar (losartan), indications, actions, and Cushing’s triad, 24 dosage of, 563 Cushing’s ulcers, 433 C-peptide, insulin, laboratory diagnosis Cutaneous larva migrans, drugs for and, 60 treating, 153t C-reactive protein (C-RP), laboratory Cutivate (fluticasone propionate), potency diagnosis and, 60 and application of, 629t Creatinine, 115 Cyanide, antidote for, 471 Index 679 Cyanocobalamin [vitamin B12] CytoGam (cytomegalovirus immune blood level of, laboratory diagnosis and, globulin), indications, actions, and 92–93 dosage of, 522 indications, actions, and dosage Cytology, of ascitic or pleural fluid, 299t of, 521 Cytomegalovirus (CMV) in total parenteral nutrition, 231t antibodies to, laboratory diagnosis and, Cyanosis, differential diagnosis of, 44 66 Cyclic antidepressants, antidote cultures for, 132 for, 471 drugs of choice for treating infections Cyclobenzaprine (Flexeril), indications, by, 146t actions, and dosage of, 521 transfusion-associated risk of Cyclocort (amcinonide), potency and transmission, 204 application of, 628t Cytomegalovirus immune globulin [CMV- Cyclogyl (cyclopentolate), indications, IVIG] (CytoGam), indications, actions, and dosage of, 521 actions, and dosage of, 522 Cyclopentolate (Cyclogyl), indications, Cytomel (liothyronine), indications, actions, and dosage of, 521 actions, and dosage of, 562 Cyclophosphamide (Cytoxan; Neosar), Cytosar-U (cytarabine), indications, indications, actions, and dosage of, actions, and dosage of, 522 521 Cytotec (misoprostol), indications, Cyclospora infection, drugs for treating, actions, and dosage of, 572 153t Cytovene (ganciclovir), indications, Cyclosporine (Neoral; Sandimmune) actions, and dosage of, 146t, half-life and therapeutic and toxic levels 543–544 of, 634t Cytoxan (cyclophosphamide), indications, indications, actions, and dosage of, actions, and dosage of, 521 521–522 Cycrin (medroxyprogesterone), indications, actions, and dosage of, D 564 Dacarbazine (DTIC), indications, actions, Cyproheptadine (Periactin), indications, and dosage of, 522 actions, and dosage of, 522 Dacliximab (Zenapax), indications, Cysteine, in urine, 117 actions, and dosage of, 522 Cysticercosis, drugs for treating, 154t Dactinomycin (Cosmegen), indications, Cysticercus cellulosae infections, drugs actions, and dosage of, 523 for treating, 154t Dalgan (dezocine), indications, actions, Cystitis, organisms responsible and and dosage of, 525 empiric therapy for, 143t Dalmane (flurazepam), indications, Cystography, 328 actions, and dosage of, 541 Cystospaz (hyoscyamine), indications, Dalteparin (Fragmin), indications, actions, actions, and dosage of, 551 and dosage of, 523 Cytadren (aminoglutethimide), Dantrolene (Dantrium), indications, indications, actions, and dosage of, actions, and dosage of, 523 495 Dapsone (Avlosulfon), indications, Cytarabine [Ara-C] (Cytosar-U), actions, and dosage of, 523 indications, actions, and dosage of, Darier’s sign, 24 522 Darkfield examination, 122 Cytarabine liposome (DepoCyt), Darvocet (propoxyphene + indications, actions, and dosage of, acetaminophen), indications, 522 actions, and dosage of, 595 680 Index Darvon (propoxyphene), indications, Dehydroepiandrosterone sulfate actions, and dosage of, 595 (DHEAS), laboratory diagnosis Darvon Compound-65 (propoxyphene + and, 66 aspirin), indications, actions, and Delavirdine (Rescriptor), indications, dosage of, indications, actions, and actions, and dosage of, 523–524 dosage of, 595 Delayed hypersensitivity skin testing, 303 Darvon-N + Aspirin (propoxyphene + Delirium, differential diagnosis of, 44 aspirin), indications, actions, and Delivery notes, 37 dosage of, indications, actions, and Del-Mycin Topical (erythromycin, dosage of, 595 topical), indications, actions, and Daunomycin (daunorubicin), indications, dosage of, 534 actions, and dosage of, 523 Delta-Cortef (prednisolone) Daunorubicin (Cerubidine; Daunomycin), dose, activity, duration, and route for, indications, actions, and dosage of, 627t 523 indications, actions, and dosage of, 603 Davonex (calcipotriene), indications, Deltasone (prednisone) actions, and dosage of, dose, activity, duration, and route for, 507–508 627t Daypro (oxaprozin), indications, actions, for hypercalcemia, 189 and dosage of, 583 indications, actions, and dosage of, 603 Daytril (acetaminophen) Demadex (torsemide), indications, antidote for, 471 actions, and dosage of, 613 indications, actions, and dosage of, 488, Demeclocycline (Declomycin), 621t indications, actions, and dosage of, route, effects, and dosage for, 321t 524 DDAVP (desmopressin), indications, Dementia, differential diagnosis of, actions, and dosage of, 524 44–45 Decadron (dexamethasone base), potency Demerol (meperidine) and application of, 628t indications, actions, and dosage Decadron (dexamethasone) of, 566 dose, activity, duration, and route for, route, effects, and dosage for, 321t 627t Demser (metyrosine), indications, actions, indications, actions, and dosage of, 603, and dosage of, 570 604 Demulen 1/35 21, 623t route, effects, and dosage for, 322t Demulen 1/50 21, 623t Decelerations, in fetal heart rate, 276 de Musset’s sign, 26 Declomycin (demeclocycline), Denavir (penciclovir), indications, actions, indications, actions, and dosage of, and dosage of, 147t, 585 524 Dennis tubes, 273 Decongestants, 487 Dental emergencies, 470 Decubitus abdominal x-rays, 326 Dental examination, 14, 17, 19f Decubitus ulcers, organisms responsible Depakene (valproic acid) and empiric therapy for, 142t half-life and therapeutic and toxic levels Deep somatic pain, 315 of, 632t Deep venous thrombosis (DVT) indications, actions, and dosage of, 616 anticoagulant standard of practice for, Depakote (divalproex), indications, 637t actions, and dosage of, 616 prevention of, 435 DepoCyt (cytarabine liposome), Dehydroepiandrosterone (DHEA), indications, actions, and dosage of, laboratory diagnosis and, 66 522 Index 681 Depo-Medrol (methylprednisolone acetate) Ophthalmic), indications, actions, dose, activity, duration, and route for, and dosage of, 524 627t Dexamethasone suppression test, 66 indications, actions, and dosage of, 603 Dexferrum (iron dextran), indications, Depo Provera (medroxyprogesterone), actions, and dosage of, 555 indications, actions, and dosage of, Dexpanthenol (Ilopan; Ilopan-choline 564 Oral) Dermalon (nylon) sutures, 346t indications, actions, and dosage of, 525 Dermatologic agents, 481 in total parenteral nutrition, 231t Dermatologic descriptions, 20–21 Dexrazoxane (Zinecard), indications, Dermatome, 22f–23f actions, and dosage of, 525 Dermatop (prednicarbate), potency and Dextran 40 (Rheomacrodex), indications, application of, 630t actions, and dosage of, 525 Desipramine (Norpramin) Dextromethorphan

(Benylin DM; half-life and therapeutic and toxic levels Mediquell; Pediacare 1), of, 633t indications, actions, and dosage of, indications, actions, and dosage of, 524 525 Desmopressin (DDAVP; Stimate), Dey-Drop (silver nitrate), indications, indications, actions, and dosage of, actions, and dosage of, 601 524 Dezocine (Dalgan), indications, actions, Desogen (Organon), 623t and dosage of, 525 Desonide (DesOwen), potency and Diabeta (glyburide), indications, actions, application of, 628t and dosage of, 545 Desoximetasone (Topicort), potency and Diabetes application of, 628t insulins for. See Insulins Desyrel (trazodone) total parenteral nutrition formulation half-life and therapeutic and toxic levels for, 235 of, 634t Diabinese (chlorpropamide), indications, indications, actions, and dosage of, 613 actions, and dosage of, 515 Detrol LA (tolterodine), indications, Diagnostic peritoneal lavage (DPL), actions, and dosage of, 612 295 DEXA, 326 Dialose (docusate potassium), indications, Dexacort Phosphate Turbinaire actions, and dosage of, 529 (dexamethasone, nasal), Diamox (acetazolamide) indications, actions, and dosage of, for hyperphosphatemia, 192 524 indications, actions, and dosage of, 489 Dexamethasone (Decadron) Diaphragm, on chest x-rays, 335, 337f dose, activity, duration, and route for, Diarrhea 627t differential diagnosis of, 45 indications, actions, and dosage of, 603, with enteral nutrition, 218, 223 604 IV fluid replacement with, 179 route, effects, and dosage for, 322t Diastolic heart murmurs, 394–395 Dexamethasone base (Aeroseb-Dex; Diastolic hypertension, 392 Decadron), potency and Diazepam (Valium) application of, 628t indications, actions, and dosage of, Dexamethasone, nasal (Dexacort 525–526 Phosphate Turbinaire), indications, for seizures, 472, 473t actions, and dosage of, 524 Diazoxide (Hyperstat; Proglycem), Dexamethasone, ophthalmic (AK-DEX indications, actions, and dosage of, Ophthalmic; Decadron 526 682 Index Dibucaine (Nupercainal), indications, Dilacor (diltiazem) actions, and dosage of, 526 for emergency cardiac care, 462 Diclofenac (Cataflam; Voltaren) indications, actions, and dosage of, 528 indications, actions, and dosage of, 526 infusion guidelines for, 439t route, effects, and dosage for, 321t Dilantin (phenytoin) Dicloxacillin (Dycill; Dynapen), half-life and therapeutic and toxic levels indications, actions, and dosage of, of, 631t–632t 526 indications, actions, and dosage of, 589 Dicyclomine (Bentyl), indications, interaction with enteral nutrition, 223 actions, and dosage of, 526 Dilaudid (hydromorphone), indications, Didanosine [DDI] (Videx), indications, actions, and dosage of, 550 actions, and dosage of, 526–527 Diltiazem (Cardizem; Dilacor; Tiazac) Didronel (etidronate disodium), for emergency cardiac care, 462 indications, actions, and dosage of, indications, actions, and dosage of, 528 536 infusion guidelines for, 439t Diet(s), hospital, 205, 206t–208t Dimenhydrinate (Dramamine), Dietary supplements, 481 indications, actions, and dosage of, Diethylcarbamazine, indications for, 153t 528 Diethylenetriamine pentaacetic acid Dimercaptosuccinic acid (technetium-99m (technetium-99m DTPA), 334 DMSA), 334 Differential diagnosis, 41–52 Dimethyl sulfoxide [DMSO] (Rimso 50), Differential WBC, 96–97, 97t indications, actions, and dosage of, Diflorasone diacetate (Psorcon), potency 528 and application of, 628t Diovan (valsartan), indications, actions, Diflucan (fluconazole), indications, and dosage of, 616 actions, and dosage of, 151t, Dipentum (olsalazine), indications, 539–540 actions, and dosage of, 580–581 Diflunisal (Dolobid), indications, actions, Diphenhydramine (Benadryl) and dosage of, 527 for anaphylaxis, 469 Digibind (digoxin immune Fab) indications, actions, and dosage for emergency cardiac care, 462 of, 528 indications, actions, and dosage of, 471, Diphenoxylate + atropine (Lomotil), 527 indications, actions, and dosage of, Digitalis 528 electrocardiogram and, 386 Diphyllobothrium latum infections, drugs toxicity of, 386 for treating, 154t Digoxin (Lanoxicaps; Lanoxin) Dipivefrin (Propine), indications, actions, antidote for, 471 and dosage of, 528 for emergency cardiac care, 462 Diplopia, differential diagnosis of, 45 half-life and therapeutic and toxic levels Diprivan (propofol), indications, actions, of, 633t and dosage of, 594 indications, actions, and dosage of, 527 Diprosone (betamethasone dipropionate), Digoxin immune Fab (Digibind) potency and application of, 628t for emergency cardiac care, 462 Dipylidium canium infections, drugs for indications, actions, and dosage of, 471, treating, 154t 527 Dirithromycin (Dynabac), indications, Dihydrohydroxycodeinone [oxycodone] actions, and dosage of, 529 (Oxycontin; OxyIR; Roxicodone), Discharge precautions, 156 indications, actions, and dosage of, Discharge summaries/notes, 34–35 583 Disopyramide (Napamide; Norpace) Index 683 half-life and therapeutic and toxic levels Dopamine (Dopastat; Intropin) of, 633t for emergency cardiac care, 462 indications, actions, and dosage indications, actions, and dosage of, of, 529 398t, 530 Disseminated intravascular coagulation infusion guidelines for, 440t (DIC), 434–435 Doppler echocardiography, 330 Distal port, of Swan-Ganz catheter, 400 Doppler pressures, 265–266 Ditropan (oxybutynin), indications, Doral (quazepam), indications, actions, actions, and dosage of, 583 and dosage of, 596 Ditropan XL (oxybutynin), indications, Dornase alfa (Pulmozyme), indications, actions, and dosage of, 583 actions, and dosage of, 530 Diuretics, 479–480 Dorzolamide (Trusopt), indications, Diuril (chlorothiazide), indications, actions, and dosage of, 530 actions, and dosage of, 515 Dorzolamide + timolol (Cosopt), Divalproex (Depakote), indications, indications, actions, and dosage of, actions, and dosage of, 616 530 Diverticulitis, organisms responsible and Doss (docusate sodium), indications, empiric therapy for, 135t actions, and dosage of, 529 Dizziness, differential diagnosis of, 45 Doxazosin (Cardura), indications, actions, DNA probes, 132 and dosage of, 530 Dobbhoff tubes, 273 Doxepin (Adapin; Sinequan) Dobutamine (Dobutrex) half-life and therapeutic and toxic levels for emergency cardiac care, 462 of, 634t indications, actions, and dosage of, indications, actions, and dosage 398t, 529 of, 530 infusion guidelines for, 439t–440t Doxepin, topical (Zonalon), indications, Docetaxel (Taxotere), indications, actions, actions, and dosage of, 531 and dosage of, 529 Doxorubicin (Adriamycin; Rubex), Docusate calcium (Surfak), indications, indications, actions, and dosage of, actions, and dosage of, 529 531 Docusate potassium (Dialose), indications, Doxycycline (Vibramycin), indications, actions, and dosage of, 529 actions, and dosage of, 153t, Docusate sodium (Colace; Doss), 531 indications, actions, and dosage of, Dramamine (dimenhydrinate), indications, 529 actions, and dosage of, 528 Döhle’s inclusion bodies, 104 Draping patients, for surgery, 343 Dolasetron (Anzemet), indications, Drawer sign, 24 actions, and dosage of, 529–530 Dronabinol (Marinol), indications, Doll’s eyes, 24 actions, and dosage of, 531 Dolobid (diflunisal), indications, actions, Droperidol (Inapsine), indications, and dosage of, 527 actions, and dosage of, 531 Dolophine (methadone) Droxia (hydroxyurea), indications, indications, actions, and dosage of, actions, and dosage of, 551 567–568 Drug interactions, with enteral nutrition, route, effects, and dosage for, 321t 223 Donnatal (hyoscyamine, atropine, DSA, 327 scopolamine, + phenobarbital), DTIC (dacarbazine), indications, actions, indications, actions, and dosage of, and dosage of, 522 551 Dukes’ classification, of colon cancer, Donor-directed blood products, 194 652 684 Index Dulcolax (bisacodyl), indications, actions, Econazole (Spectazole), indications, and dosage of, 505 actions, and dosage of, 531–532 Duodenal ulcers, organism responsible Edecrin (ethacrynic acid), indications, and empiric therapy for, 144t actions, and dosage of, 536 Duo-Tube, 273 Edema, differential diagnosis of, 46 Dupuytren’s contracture, 25 Edex (alprostadil, intracavernosal), Duragesic (fentanyl, transdermal), indications, actions, and dosage of, indications, actions, and dosage of, 492 538 Edrophonium (Tensilon), indications, Duramorph (morphine) actions, and dosage of, 532 for emergency cardiac care, 465 Education, assertiveness in obtaining, 3 indications, actions, and dosage of, 573 Efavirenz (Sustiva), indications, actions, route, effects, and dosage for, 321t and dosage of, 532 Duricef (cefadroxil) Effer-Syllium (psyllium), indications, indications, actions, and dosage of, 511 actions, and dosage of, 596 for subacute bacterial endocarditis Effexor (venlafaxine), indications, actions, prophylaxis, 158t and dosage of, 617 Duroziez’s sign, 25 Efudex (fluorouracil, topical), indications, Duvoid (bethanechol), indications, actions, and dosage of, 541 actions, and dosage of, 504–505 Ehrlichiosis, characteristics and treatment Dyazide (hydrochlorothiazide + of, 156t–157t triamterene), indications, actions, Elavil (amitriptyline) and dosage of, 549 indications, actions, and dosage Dycill (dicloxacillin), indications, actions, of, 495 and dosage of, 526 route, effects, and dosage for, 322t Dynabac (dirithromycin), indications, Eldepryl (selegiline), indications, actions, actions, and dosage of, 529 and dosage of, 600 Dynacirc (isradipine), indications, actions, Electrical alternans, 25 and dosage of, 555–556 Electrical defibrillation, 467–468 Dynamic compliance, 417–418 Electrical stimulation, for pain Dynapen (dicloxacillin), indications, management, 323 actions, and dosage of, 526 Electrocardiograms (ECGs), 266–268, Dyrenium (triamterene), indications, 367–388, 368f, 369f actions, and dosage of, 613–614 atrial arrhythmias on, 372–374, Dysmorphic red cells, 114–115 373f–375f Dysphagia, differential diagnosis of, 45 axis deviation in, 369–370, 370f Dyspnea, differential diagnosis of, 45 in cardiac hypertrophy, 380–383, Dysuria, differential diagnosis of, 46 381f–383f drug effects on, 386 electrolyte effects on, 385–386, 386f E heart blocks on, 377–379, 379f–381f Ear(s), medications for, 482 heart rate and, 371, 371f Earache, differential diagnosis of, 46 hypothermia, 387f, 388 Ecchymoses, 20 in hypothermia, 387f, 388 Echinococcus granulosus infections, drugs indications for, 266 for treating, 154t leads for, 368 Echocardiography, 330 materials for, 266 Echothiophate iodine (Phospholine in myocardial infarction, 383f–385f, Ophthalmic), indications, actions, 383–384, 385t and dosage of, 532 nodal rhythm on, 374–375, 376f Index 685 normal ECG complex and, 368f, Empirin No. 2, No. 3, No. 4 (aspirin + 368–369 codeine), indications, actions, and paper for, 368 dosage of, 500 in pericarditis, 387, 387f Empyema, 50 procedure for, 266–268, 267f organisms responsible and empiric sinus rhythms on, 371–372, 372f–373f therapy for, 136t standardization for, 367, 368f E-mycin (erythromycin), indications, ventricular arrhythmias on, 375–377, actions, and dosage of, 533–534 376f–378f Enalapril (Vasotec) in Wolff-Parkinson-White syndrome, for emergency cardiac care, 449 388, 388f indications, actions, and dosage of, 532 Electrolytes. See also Fluids and Enalaprilat IV, for emergency cardiac care, electrolytes; specific electrolytes 449 electrocardiograms and, 385–386, 386f Encephalitis, herpes simplex virus, drugs spot urine study for, 114 of choice for treating, 147t Electromyography, for pain evaluation, Endobronchial endoscopic collection, 130 319 Endocarditis, bacterial Elemental formulas, for enteral nutrition, organisms responsible and empiric 217 therapy for, 136t–137t Elimite (permethrin), indications, actions, subacute, prophylaxis of, 155, and dosage of, 153t, 154t, 588 158t–159t Elmiron (pentosan polysulfate sodium), Endocrine system, medications for, 482 indications, actions, and dosage of, Endotracheal intubation, 268–270 587 contraindications to, 268 Elocon (mometasone furoate), potency indications for, 268 and application of, 630t materials for, 268, 269t Elspar (L-asparaginase), indications, technique for, 268–270, 270f actions, and dosage of, 499 Endovaginal ultrasound, 329 Embolism, prevention of, anticoagulant Enfamil 20, 224t standard of practice for, 637t Enfamil 24, 224t Emcyt (estramustine phosphate), Enfamil Premature 20, 225t indications, actions, and dosage of, Enfamil Special Care 24, 225t 535 Engerix-B (hepatitis B vaccine), Emergency cardiac care (ECC), indications, actions, and dosage of, 449–468 548 algorithms for, 450f–460f Enoxaparin (Lovenox), indications, drugs used in, 449, 461–467 actions, and dosage of, 532 electrical defibrillation and Entacapone (Comtan), indications, cardioversion for, 467–468 actions, and dosage of, 532 Emergency transfusions, 194 Entamoeba histolytica infections, drugs Emesis, IV fluid replacement for, 179 for treating, 153t Emgel Topical (erythromycin, topical), Enteral nutrition, 213, 214t, 214–223 indications, actions, and dosage of, complications of, 218, 223 534 initiating tube feedings for, 217–218, Eminase (anistreplase) 218t–222t for emergency cardiac care, 467 postoperative, 223 indications, actions, and dosage of, 498 products for, 214, 215t–216t, 217 EMLA (lidocaine + prilocaine), Enteric precautions, 155 indications, actions, and dosage of, Enterobacter, Gram stain characteristics 561 of, 124f 686 Index Enterobius vermicularis infections, drugs ERCP (endoscopic retrograde for treating, 153t cholangiopancreatography), 328 Enteroclysis, 328 Erectile dysfunction, differential diagnosis Enterococcus, Gram stain characteristics of, 48 of, 123f, 125t Ergamisol (levamisole), indications, Entriflex tubes, 273 actions, and dosage of, 560 Entuss-D (hydrocodone + Erosions, cutaneous, 20 pseudoephedrine), indications, Erysipelas, organism responsible and actions, and dosage of, 550 empiric therapy for, 142t Enzone (pramoxine + hydrocortisone), Erythrocin (erythromycin), indications, indications, actions, and dosage of, actions, and dosage of, 533–534 592 Erythrocytapheresis, 194 Enzymes, 484 Erythrocytes. See Red blood cell(s) Eosinophils, laboratory diagnosis and, 101 (RBCs) Ephedrine, indications, actions, and Erythrocyte sedimentation rate (ESR), 108 dosage of, 532–533 Erythromycin (E-mycin; Erythrocin; Epidemiology, 639, 645 Ilosone), indications, actions, and Epiglottitis, 131 dosage of, 533–534 organisms responsible and empiric Erythromycin + benzoyl peroxide therapy for, 137t (Benzamycin), indications, actions, Epinephrine, racemic, 364 and dosage of, 534 Epinephrine (Adrenalin; Sus-Phrine) Erythromycin, ophthalmic (Ilotycin actions of, 398t Ophthalmic), indications, actions, for anaphylaxis, 468, 469 and dosage of, 534 for asthmatic attacks, 469 Erythromycin + sulfisoxazole (Eryzole; for emergency cardiac care, 462 Pediazole), indications, actions, indications, actions, and dosage and dosage of, 534 of, 533 Erythromycin, topical (Akne-Mycin infusion guidelines for, 440t Topical; Del-Mycin Topical; for suturing, 348, 349t Emgel Topical; Staticin Topical), Epistaxis, differential diagnosis of, 46 indications, actions, and dosage of, Epithelial casts, in urine sediment, 114 534 Epithelial cells, in urine sediment, 112 Erythropoietin [epoetin alfa] (Epogen; Epivir (lamivudine), indications, actions, Procrit), indications, actions, and and dosage of, 146t, 558 dosage of, 533 Epivir-HBV (lamivudine), indications, Erythropoietin (EPO), laboratory actions, and dosage of, 146t, 558 diagnosis and, 66–67 Epoetin alfa [erythropoietin] (Epogen; Eryzole (erythromycin + sulfisoxazole), Procrit), indications, actions, and indications, actions, and dosage of, dosage of, 533 534 Epoprostenol (Flolan), indications, Escherichia coli, Gram stain actions, and dosage of, 533 characteristics of, 124f, 126t Eprosartan (Teveten), indications, actions, Esidrix (hydrochlorothiazide), indications, and dosage of, 533 actions, and dosage of, 549 Epstein-Barr virus (EBV), 146t Eskalith (lithium

carbonate), indications, Eptifibatide (Integrilin) actions, and dosage of, 562 for emergency cardiac care, 464 Esmolol (Brevibloc) indications, actions, and dosage of, 533 for emergency cardiac care, 462 Equanil (meprobamate), indications, indications, actions, and dosage of, 534 actions, and dosage of, 566 infusion guidelines for, 440t Index 687 Esophageal procedures, subacute bacterial Estrogen(s), esterified + endocarditis prophylaxis for, 158t methyltestosterone (Estratest), Esophagitis, cytomegalovirus, drugs of indications, actions, and dosage of, choice for treating, 146t 535 Esophagography, 328 Estrogen receptors, laboratory diagnosis Estazolam (Prosom), indications, actions, and, 67 and dosage of, 534 Estrogen supplementation, 485 Estinyl (ethinyl estradiol), indications, Estrostep 28, 624t actions, and dosage of, 536 Ethacrynic acid (Edecrin), indications, Estrace (estradiol), indications, actions, actions, and dosage of, 536 and dosage of, 535 Ethambutol (Myambutol), Estracyte (estramustine phosphate), indications, actions, and dosage indications, actions, and dosage of, of, 536 535 Ethanol Estraderm (estradiol, transdermal), blood levels of, laboratory diagnosis indications, actions, and dosage of, and, 67 535 for methanol poisoning, 471 Estradiol (Estrace), indications, actions, Ethibond (polyester) sutures, 347t and dosage of, 535 Ethilon (nylon) sutures, 346t Estradiol, serum, laboratory diagnosis and, Ethinyl estradiol (Estinyl; Feminone), 67 indications, actions, and dosage of, Estradiol, transdermal (Estraderm), 536 indications, actions, and dosage of, Ethmozine (moricizine), indications, 535 actions, and dosage of, 573 Estramustine phosphate (Emcyt; Ethosuximide (Zarontin) Estracyte), indications, actions, half-life and therapeutic and toxic levels and dosage of, 535 of, 631t Estratab (estrogens, esterified), indications, actions, and dosage indications, actions, and dosage of, of, 536 535 Ethyol (amifostine), indications, actions, Estratest (estrogens, esterified + and dosage of, 494 methyltestosterone), indications, Etidronate disodium (Didronel), actions, and dosage of, 535 indications, actions, and dosage of, Estrogen(s), conjugated (Premarin), 536 indications, actions, and dosage of, Etodolac (Lodine), indications, actions, 535 and dosage of, 536–537 Estrogen(s), conjugated + Etoposide [VP-16] (Vepesid), indications, methylprogesterone (Premarin + actions, and dosage of, 537 Methylprogesterone), indications, Eubacterium, Gram stain characteristics actions, and dosage of, 535–536 of, 126t Estrogen(s), conjugated + Eulexin (flutamide), indications, actions, methyltestosterone (Premarin + and dosage of, 541–542 Methyltestosterone), indications, Eumorphic blood cells, 114 actions, and dosage of, 536 Euvolemic hypernatremia, 184–185 Estrogen(s), conjugated-synthetic Evening rounds, 3–4 (Cenestin), indications, actions, Evista (raloxifene), indications, actions, and dosage of, 535–536 and dosage of, 597 Estrogen(s), esterified (Estratab; Menest), Ewald tubes, 273 indications, actions, and dosage of, Ewart’s sign, 25 535 Excoriations, 21t 688 Index Exosurf Neonatal (colfosceril palmitate), Femara (letrozole), indications, actions, indications, actions, and dosage of, and dosage of, 559 520 Feminone (ethinyl estradiol), indications, Expiratory chest x-rays, 325 actions, and dosage of, 536 Expiratory reserve volume (ERV), 416 Femoral vein, venipuncture using, 313 Exsel Shampoo (selenium sulfide), Fenofibrate (Tricor), indications, actions, indications, actions, and dosage of, and dosage of, 537 600 Fenoldopam (Corlopam), indications, Extremity perfusion, 392 actions, and dosage of, 537 Extrinsic factor, laboratory diagnosis and, Fenoprofen (Nalfon), indications, actions, 92–93 and dosage of, 537–538 Extubation, from mechanical ventilation, Fentanyl (Sublimaze) 428–429 indications, actions, and dosage of, 538 ExU (excretory urography), 328 route, effects, and dosage for, 321t Exudative ascites, 297 Fentanyl Oralet (fentanyl, transmucosal Eyes, medications for, 482–483 system), indications, actions, and dosage of, 538 Fentanyl, transdermal (Duragesic), F indications, actions, and dosage of, Factor VII, for transfusion, 199t 538 Factor VIII [antihemophilic factor] Fentanyl, transmucosal system (Actiq; (Monoclate) Fentanyl Oralet), indications, indications, actions, and dosage of, 498 actions, and dosage of, 538 for transfusion, 199t Fergon (ferrous gluconate), indications, Factor IX concentrate, 200t actions, and dosage of, 538 Fahrenheit/celsius conversion, 646, 649t Ferric gluconate complex (Ferrlecit), Failure to thrive, differential diagnosis of, indications, actions, and dosage of, 46 538 Famciclovir (Famvir), indications, actions, Ferritin, laboratory diagnosis and, 68 and dosage of, 147t, 148t, 537 Ferrlecit (ferric gluconate complex), Family history, 10 indications, actions, and dosage of, Famotidine (Pepcid), indications, actions, 538 and dosage of, 537 Ferrous gluconate (Fergon), indications, Famvir (famciclovir), indications, actions, actions, and dosage of, 538 and dosage of, 147t, 148t, 537 Ferrous sulfate, indications, actions, and Fast catgut sutures, 346t dosage of, 538 Fat, fecal, laboratory diagnosis and, 67 Fetal heart rate, internal fetal scalp Fat restricted diet, 208t monitoring of, 275–276 Fatty casts, in urine sediment, 114 Fetal scalp monitoring, internal, 275–276 Febrile reactions, to transfusions, Fever nonhemolytic, 202 differential diagnosis of, 46 Fecal fat, laboratory diagnosis and, 67 of unknown origin, differential Fecal leukocytes, 128 diagnosis of, 46 Feeding tubes, 273 Fever work-up, 270–272 Feldene (piroxicam) Fexofenadine (Allegra), indications, indications, actions, and dosage of, 590 actions, and dosage of, 538–539 route, effects, and dosage for, 321t Fibrin D-Dimers, 107 Fellows, 2 Fibrin degradation products (FDPs), 107 Felodipine (Plendil), indications, actions, Fibrinogen, 107 and dosage of, 537 Fibrin split products (FSPs), 107 Index 689 FIGO classification, 655, 657 Flovent (fluticasone, oral), indications, Filariasis, drugs for treating, 153t actions, and dosage of, 542 Filgrastim [G-CSF] (Neupogen), Flovent Rotadisk (fluticasone, oral), indications, actions, and dosage of, indications, actions, and dosage of, 539 542 Finasteride (Propecia; Proscar), Floxin (ofloxacin), indications, actions, indications, actions, and dosage of, and dosage of, 580–581 539 Floxuridine (FUDR), indications, actions, Fioricet (acetaminophen + butalbital +/- and dosage of, 539 caffeine), indications, actions, and Fluconazole (Diflucan), indications, dosage of, 489 actions, and dosage of, 151t, Fiorinal (aspirin + butalbital compound), 539–540 indications, actions, and dosage of, 5-Flucytosine, indications for, 151t 500 Fludarabine phosphate (Flamp; Fludara), Fiorinal + Codeine (aspirin + butalbital, indications, actions, and dosage of, caffeine and codeine), indications, 540 actions, and dosage of, 500 Fludrocortisone, for renal tubular acidosis, First-degree heart block, 377, 379f 168t Fissures, cutaneous, 21t Fludrocortisone acetate (Florinef), Fistulography, 328 indications, actions, and dosage of, Flagyl (metronidazole), indications, 540 actions, and dosage of, 153t, 154t, Fluids and electrolytes, 177–192. See also 570 Intravenous (IV) fluids Flamp (fludarabine phosphate), baseline fluid requirement and, 178 indications, actions, and dosage of, electrolyte abnormality diagnosis and 540 treatment, 184–192 Flat and upright abdominal x-rays, 326 electrolyte requirements and, 178 Flat plates, 326 fluid compartments and, 177 Flatulence, differential diagnosis of, 47 glucose requirements and, 178 Flavoxate (Urispas), indications, actions, IV rate determination for, 183–184 and dosage of, 539 maintenance fluids, 179, 181t Flecainide (Tambocor) ordering IV fluids, 179–183 half-life and therapeutic and toxic levels parenteral fluid composition and, of, 633t 178–179 indications, actions, and dosage red blood cell mass and, 177 of, 539 specific replacement fluids, 179, Fleet’s Phospho-soda (sodium phosphate), 182f–183f, 183 for hypophosphatemia, 192 total blood volume and, 177 Flexeril (cyclobenzaprine), indications, total body water, 177 actions, and dosage of, 521 water balance and, 177–178 Flexible sigmoidoscopy, 300 Flumadine (rimantadine), indications, Flolan (epoprostenol), indications, actions, actions, and dosage of, 148t, and dosage of, 533 598–599 Flomax (tamsulosin), indications, actions, Flumazenil (Romazicon) and dosage of, 607 for benzodiazepine poisoning, 471 Flonase (fluticasone, nasal), indications, for emergency cardiac care, 462 actions, and dosage of, 542 indications, actions, and dosage of, 540 Florinef (fludrocortisone acetate), Flunisolide (Aerobid; Nasolide), indications, actions, and dosage of, indications, actions, and dosage of, 540 540 690 Index Fluocinolone acetonide (Synalar; Synalar- Folex (methotrexate) HP), potency and application of, half-life and therapeutic and toxic levels 628t, 629t of, 633t Fluocinonide (Lidex; Lidex-E), potency indications, actions, and dosage of, 568 and application of, 629t Foley catheter, 307, 307f Fluogen (influenza vaccine), indications, Folic acid actions, and dosage of, 553 blood levels of, laboratory diagnosis Fluorescent treponemal antibody absorbed and, 68 (FTS-ABS), laboratory diagnosis indications, actions, and dosage of, 542 and, 68 in total parenteral nutrition, 231t Fluoroquinolones, 477 Follicle-stimulating hormone (FSH), Fluorouracil [5-FU] (Adrucil), indications, laboratory diagnosis and, 68 actions, and dosage of, 540 Fomivirsen (Vitravene), indications and Fluorouracil, topical [5-FU] (Efudex), dosage for, 146t indications, actions, and dosage of, Fong lesion/syndome, 25 541 Food fibers, in ascitic fluid, 299t Fluoxetine (Prozac; Sarafem), indications, Forced expired volume in 1 second actions, and dosage of, 541 (FEV/d1/D), 360, 361t Fluoxymesterone (Halotestin), Forced vital capacity (FVC), 360, 361t indications, actions, and dosage Fortaz (ceftazidime), indications, actions, of, 541 and dosage of, 513 Fluphenazine (Permitil; Prolixin), Fortovase (saquinavir), indications, indications, actions, and dosage of, actions, and dosage of, 150t, 600 541 Fosamax (alendronate), indications, Flurandrenolide (Cordran), potency and actions, and dosage of, 491 application of, 629t Foscarnet (Foscavir) Flurazepam (Dalmane), indications, indications, actions, and dosage of, 542 actions, and dosage of, 541 indications and dosage for, 146t, 147t, Flurbiprofen (Ansaid), indications, 149t actions, and dosage of, 541 Fosfomycin (Monurol), indications, Flushield (influenza vaccine), indications, actions, and dosage of, 542–543 actions, and dosage of, 553 Fosinopril (Monopril), indications, Flutamide (Eulexin), indications, actions, actions, and dosage of, 543 and dosage of, 541–542 Fosphenytoin (Cerebryx) Fluticasone, nasal (Flonase), indications, indications, actions, and dosage of, 543 actions, and dosage of, 542 for seizures, 473t Fluticasone, oral (Flovent; Flovent Fourth heart sound (S4), 17t Rotadisk), indications, actions, and Fragmin (dalteparin), indications, actions, dosage of, 542 and dosage of, 523 Fluticasone propionate (Cutivate), Frank’s sign, 25 potency and application of, 629t French units, 240, 241f Fluvastatin (Lescol), indications, actions, Frequency, urinary, differential diagnosis and dosage of, 542 of, 47 Fluvirin (influenza vaccine), indications, Fresh frozen plasma (FFP), 198t–199t actions, and dosage of, 553 FUDR (floxuridine), indications, actions, Fluvoxamine (Luvox), indications, and dosage of, 539 actions, and dosage of, 542 Full liquid diet, 206t Fluzone (influenza vaccine), indications, Functional residual capacity (FRC), 360, actions, and dosage of, 553 361t, 416, 416f, 417f Index 691 Fungal infections, systemic drugs for indications, actions, and dosage of, 544 treating, 151t–152t for subacute bacterial endocarditis Fungal serologies, laboratory diagnosis prophylaxis, 159t and, 68 Garamycin (gentamicin, ophthalmic), Fungizone (amphotericin B), indications, indications, actions, and dosage of, actions, and dosage of, 151t, 544 496–497 Garamycin (gentamicin, topical), Furadantin Macrobid (nitrofurantoin), indications, actions, and dosage of, indications, actions, and dosage of, 545 579 Gastric cancer, staging of, 656 Furosemide (Lasix) Gastric loss, IV fluid replacement with, for emergency cardiac care, 462–463 179 indications, actions, and dosage of, 543 Gastric ulcers, organism responsible and for renal tubular acidosis, 168t empiric therapy for, 144t Fusobacterium, Gram stain characteristics Gastrin, serum, laboratory diagnosis and, of, 126t 69 Gastroenteritis, organisms responsible and empiric therapy for, G 137t–138t Gabapentin (Neurontin), indications, Gastrografin enema, 328 actions, and dosage of, 543 Gastrointestinal agents, 483–484 Gabitril (tiagabine), indications, actions, Gastrointestinal intubation, 272–274 and dosage of, 610 complications of, 274 Galactorrhea, differential diagnosis of, 47 indications for, 272 Gallium nitrate (Ganite) materials for, 272 for hypercalcemia, 189 procedure for, 273–274 indications, actions, and dosage of, 543 tubes for, 272–273 Gallium scans, 334 Gastrointestinal procedures, subacute Gallops, 394 bacterial endocarditis prophylaxis Gamimmune N (immune globulin, for, 158t, 159t intravenous), indications, actions, Gatifloxacin (Tequin), indications, and dosage of, 552 actions, and dosage of, 544 Gamma globulin, indications and dosage Gaviscon (alginic acid + aluminum for, 146t hydroxide and magnesium Gamma-glutamyl transpeptidase, serum trisilicate), indications, actions, (SGGT), laboratory diagnosis and, and dosage of, 491 69 Gaviscon (aluminum hydroxide + Gammar IV (immune globulin, magnesium carbonate), intravenous), indications, actions, indications, actions, and dosage of, and dosage of, 552 493 Ganciclovir (Cytovene; Vitrasert), Gaviscon (aluminum hydroxide + indications, actions, and dosage of, magnesium trisilicate), indications, 146t, 543–544 actions, and dosage of, 493 Ganite (gallium nitrate) Gaviscon-2 (aluminum hydroxide + for hypercalcemia, 189 magnesium trisilicate), indications, indications, actions, and dosage of, 543 actions, and dosage of, 493 Garamycin (gentamicin) GC culture, 291 half-life and therapeutic and toxic levels Gemzar (gemcitabine), indications, of, 631t actions, and dosage of, 544 692 Index Genital herpes, drugs of choice for Glucagon treating, 147t for beta blocker poisoning, 471 Genital warts, drugs of choice for treating, for emergency cardiac care, 464 148t indications, actions, and dosage of, 545 Genitourinary agents, 487 Glucophage (metformin), indications, Genitourinary procedures, subacute actions, and dosage of, 567 bacterial endocarditis prophylaxis Glucose for, 159t laboratory diagnosis and, 69 Genoptic (gentamicin, ophthalmic), in pleural fluid, 299t indications, actions, and dosage of, requirement for, 178 544 in urine, 111 Genora 1/35 21, 28, 623t Glucose tolerance test (GTT), 69–70 Genora 1/50 28, 623t oral, 69–70 Gentacidin (gentamicin, ophthalmic), Glucotrol (glipizide), indications, actions, indications, actions, and dosage of, and dosage of, 545 544 Glu-K (potassium gluconate), form and Gentak (gentamicin, ophthalmic), dosage of, 626t indications, actions, and dosage of, Glyburide (Diabeta; Micronase), 544 indications, actions, and dosage of, Gentamicin (Garamycin) 545 half-life and therapeutic and toxic levels Glycerin suppositories, indications, of, 631t actions, and dosage of, 545–546 indications, actions, and dosage Glycohemoglobin (GHB), laboratory of, 544 diagnosis and, 70 for subacute bacterial endocarditis Glycoprotein IIb/IIIa inhibitors, for prophylaxis, 159t emergency cardiac care, 464 Gentamicin, ophthalmic (Garamycin; Glyset (miglitol), indications, actions, and Genoptic; Gentacidin; Gentak), dosage of, 571 indications, actions, and

dosage of, G-Myticin (gentamicin, topical), 544 indications, actions, and dosage of, Gentamicin + prednisolone, ophthalmic 545 (Pred-G Ophthalmic), indications, GoLYTELY (polyethylene glycol [PEG]- actions, and dosage of, 545 electrolyte solution), indications, Gentamicin, topical (Garamycin; actions, and dosage of, 590–591 G-Myticin), indications, actions, Gonadorelin (Lutrepulse), indications, and dosage of, 545 actions, and dosage of, 546 Geriatrics, total parenteral nutrition Gonococcal antigen assay, 129 formulation for, 235 Gonorrhea Giardiasis, drugs for treating, 153t cultures and smear for, 129 Gibbus, 25 organism responsible and empiric Giemsa stain, 122 therapy for, 138t Glasgow Coma Scale (EMV Scale), 645, Gonozyme, 129 645t Goserelin (Zoladex), indications, actions, Glaucoma agents, 482–483 and dosage of, 546 Glimepiride (Amaryl), indications, Gowning, for operating room, 342–343 actions, and dosage of, 545 Gram stain, 122, 291 Glipizide (Glucotrol), indications, actions, of common pathogens, 122, 123f–124f, and dosage of, 545 125t–127t Glitter cells, in urine sediment, 114 Granisetron (Kytril), indications, actions, Gloving, for operating room, 342–343 and dosage of, 546 Index 693 Granulocytes, for transfusion, 197t Haldol (haloperidol) Granuloma inguinale, organism indications, actions, and dosage of, 547 responsible and empiric therapy route, effects, and dosage for, 322t for, 138t Halobetasol (Ultravate), potency and Granulomatous infection, cerebrospinal application of, 629t fluid in, 287t Halog (halcinonide), potency and Gregg’s triad, 25 application of, 629t Grey Turner’s sign, 25 Haloperidol (Haldol) Grocco’s sign, 25 indications, actions, and dosage of, 547 Guaifenesin (Robitussin), indications, route, effects, and dosage for, 322t actions, and dosage of, 546 Haloprogin (Halotex), indications, actions, Guaifenesin + codeine (Brontex; and dosage of, 547 Robitussin A-C), indications, Halotestin (fluoxymesterone), indications, actions, and dosage of, 546 actions, and dosage of, 541 Guaifenesin + dextromethorphan, Halotex (haloprogin), indications, actions, indications, actions, and dosage of, and dosage of, 547 546 Hampton’s hump, 436 Guanabenz (Wytensin), indications, Hand scrub, surgical, 340–341 actions, and dosage of, Haptoglobin, laboratory diagnosis and, 70 546–547 Harris-Benedict BEE, 209 Guanadrel (Hylorel), indications, actions, Havrix (hepatitis A vaccine), indications, and dosage of, 547 actions, and dosage of, 548 Guanethidine (Ismelin), indications, H-BIG (hepatitis B immune globulin), actions, and dosage of, 547 indications, actions, and dosage of, Guanfacine (Tenex), indications, actions, 548 and dosage of, 547 HDL-C (high-density lipoprotein Guillain-Barré syndrome, cerebrospinal cholesterol), laboratory diagnosis fluid in, 287t and, 63 Gynecologic agents, 485–486 Headache Gynecomastia, differential diagnosis of, differential diagnosis of, 47 47 spinal, 286 Head computed tomography, 330 Head magnetic resonance imaging, 332–333 H Healing, of wounds, 345 Habitrol (nicotine, transdermal), Health, personal, 2–3 indications, actions, and dosage of, Heart, on chest x-rays, 335, 336f, 337f 578 Heart blocks, on electrocardiograms, Haemophilus B conjugate vaccine 377–379, 379f–381f (Comvax; Prohibit), indications, Heartburn, differential diagnosis of, 47 actions, and dosage of, 547 Heart murmurs, 16t–17t, 18f, 393–395 Haemophilus ducreyi, Gram stain Heart rate characteristics of, 126t on electrocardiograms, 371, 371f Haemophilus influenza, Gram stain measurement of, 408 characteristics of, 124f, 126t Heart sounds, extra, 16t–17t Hairworm infection, drugs for treating, Heberden’s nodes, 25 154t Heelstick, 274, 275f Halcinonide (Halog), potency and Hegar’s sign, 25 application of, 629t Helical computed tomography, 331 Halcion (triazolam), indications, actions, Helicobacter pylori antibody titers, and dosage of, 614 laboratory diagnosis and, 70 694 Index Hellenhorst’s plaque, 25 drugs of choice for treating, 148t, 149t Helmet cells, 104 Hetastarch (Hespan), indications, actions, Hematemesis, differential diagnosis of, 47 and dosage of, 548 Hematochezia, differential diagnosis of, Hexalen (altretamine), indications, 47 actions, and dosage of, 493 Hematocrit, 97, 101 Hibiclens 6-min hand scrub, 341 Hematologic agents, 484 Hiccups, differential diagnosis of, 48 Hematuria, differential diagnosis of, 48 HIDA-scans, 334 Hemoccult test, 89, 300 High-density formulas, for enteral Hemodialysis, diet for, 207 nutrition, 217 Hemopoietic stimulants, 484 High-density lipoprotein cholesterol Hemoptysis, differential diagnosis of, 48 (HDL), laboratory diagnosis and, Hemorrhage, synovial fluid interpretation 63 and, 250, 251t Higher osmolality infant formulas, 224t Henderson equation, 162 High-frequency ventilation, 424, 426 Henderson-Hasselbalch equation, 162 Hill’s sign, 25 Heparin Hilum, on chest x-rays, 335 indications, actions, and dosage of, 548 131 Hippuran, 334 low molecular weight, for emergency Hiprex (methenamine), indications, cardiac care, 464 actions, and dosage of, 568 for pulmonary embolism, 436 Hirsutism, differential diagnosis unfractionated, for emergency cardiac of, 48 care, 464 Histoplasmosis, systemic drugs for Hepatitis treating, 151t drugs of choice for treating, 146t–147t History, 9–11 transfusion-associated risk of psychiatric, 13–14 transmission, 203 written, 5, 28–32 Hepatitis A vaccine (Havrix; Vaqta), Histussin D (hydrocodone + indications, actions, and dosage of, pseudoephedrine), indications, 548 actions, and dosage of, 550 Hepatitis B immune globulin (H-BIG; Hivid (zalcitabine), indications, actions, Hyperhep), indications, actions, and dosage of, 619 and dosage of, 548 Hoffmann’s sign/reflex, 25 Hepatitis B vaccine (Engerix-B; Holoxan (ifosfamide), indications, actions, Recombivax-HB), indications, and dosage of, 552 actions, and dosage of, 548 Homans’ sign, 25 Hepatitis testing, 70, 71t–72t, 73f, 74 Homocysteine, serum, laboratory for hepatitis A, 72t, 73f, 74 diagnosis and, 75 for hepatitis B, 72t, 73f, 74 Hookworm infections, drugs for treating, for hepatitis C, 72t, 74 153t Hepatobiliary scans, 334 Hormones, 482. See also specific Hepatomegaly, differential diagnosis of, hormones 48 antineoplastic, 478 Herpes cultures, 291 gynecologic agents, 485 Herpes simplex virus (HSV) Horner’s syndrome, 25 cultures for, 132 Hospital diets, 205, 206t–208t drugs of choice for treating infections Hounsfield units, 330 by, 147t House diet, 206t Herpes zoster. See also Varicella zoster Household measurement units, 646 virus (VZV) Howell-Jolly bodies, 104 Index 695 Humalog (lispro), onset, peak, and acetaminophen, + caffeine), duration of effect of, 622t indications, actions, and dosage of, Humalog Mix (lispro protamine/lispro), 550 onset, peak, and duration of effect Hycort (hydrocortisone) of, 622t indications, actions, and dosage Human chorionic gonadotropin (hCG), of, 550 serum, laboratory diagnosis and, potency and application of, 629t 75 Hycotuss Expectorant (hydrocodone + Human granulocytic ehrlichiosis, guaifenesin), indications, actions, characteristics and treatment of, and dosage of, 550 156t–157t Hydralazine (Apresoline), indications, Human immunodeficiency virus (HIV) actions, and dosage of, 549 infection Hydrea (hydroxyurea), indications, drugs of choice for treating, 150t actions, and dosage of, 551 transfusion-associated risk of Hydrochlorothiazide (Esidrix; transmission, 203–204 Hydrodiuril), indications, actions, Human immunodeficiency virus (HIV) and dosage of, 549 testing, 75–77, 76f Hydrochlorothiazide + amiloride HIV antibody and, 75 (Moduretic), indications, actions, HIV antibody by ELISA determination and dosage of, 549 and, 76 Hydrochlorothiazide + spironolactone HIV antibody ELISA and, 75–76 (Aldactazide), indications, actions, HIV antigen and, 77 and dosage of, 549 HIV core antigen and, 83 Hydrochlorothiazide + triamterene HIV DNA PCR and, 77 (Dyazide; Maxzide), indications, HIV RNA PCR and, 77 actions, and dosage of, 549 HIV viral load and, 77 Hydrocodone + acetaminophen (Lorcet; HIV Western blot and, 76 Vicodin), indications, actions, and Human leukocyte antigens (HLA), dosage of, 549 laboratory diagnosis and, 74–75 Hydrocodone + aspirin (Lortab ASA), Human milk, 224t indications, actions, and dosage of, Human papillomavirus (HPV), drugs of 549 choice for treating infections by, Hydrocodone, chlorpheniramine, 148t phenylephrine, acetaminophen, Human T-cell leukemia virus type 1 + caffeine (Hycomine), (HTLV-1), transfusion-associated indications, actions, and dosage risk of transmission, 204 of, 550 Humidity therapy, 362, 363t Hydrocodone + guaifenesin (Hycotuss Humulin N, onset, peak, and duration of Expectorant), indications, actions, effect of, 622t and dosage of, 550 Humulin U, onset, peak, and duration of Hydrocodone + homatropine (Hycodan), effect of, 622t indications, actions, and dosage of, Hyaline casts, in urine sediment, 114 550 Hycamtin (topotecan), indications, Hydrocodone + ibuprofen (Vicoprofen), actions, and dosage of, 612 indications, actions, and dosage of, Hycodan (hydrocodone + homatropine), 550 indications, actions, and dosage of, Hydrocodone + pseudoephedrine 550 (Entuss-D; Histussin D), Hycomine (hydrocodone, indications, actions, and dosage chlorpheniramine, phenylephrine, of, 550 696 Index Hydrocortisone (CaldeCort; Cortizone; Hyoscyamine, atropine, scopolamine, + Hycort; Hytone) phenobarbital (Donnatal), indications, actions, and dosage of, 550 indications, actions, and dosage of, potency and application of, 629t 551 Hydrocortisone (Hydrocortone; Solu- Hyperalimentation. See Total parenteral Cortef) nutrition (TPN) dose, activity, duration, and route for, Hypercalcemia, 188–189 627t electrocardiogram and, 386 for hypercalcemia, 189 Hypercalcemia agents, 482 indications, actions, and dosage of, Hyperchloremic acidosis, 166, 168t 603–604 Hyperhep (hepatitis B immune globulin), Hydrocortisone acetate (Corticaine) indications, actions, and dosage of, indications, actions, and dosage of, 603 548 potency and application of, 629t Hyperkalemia, 186–187 Hydrocortisone butyrate (Locoid), potency electrocardiogram and, 385, 386f and application of, 629t total parenteral nutrition for, 237 Hydrocortisone sodium, for asthmatic Hypermagnesemia, 190 attacks, 469 total parenteral nutrition for, 237 Hydrocortisone succinate, indications, Hypernatremia, 184–185 actions, and dosage of, 603 Hyperosmolar nonketotic coma, total Hydrocortisone valerate (Westcort), parenteral nutrition for, 236 potency and application of, 629t Hyperparathyroidism, hypercalcemia Hydrocortone (hydrocortisone) with, 188 dose, activity, duration, and route for, 627t Hyperphosphatemia, 191–192 for hypercalcemia, 189 Hypersegmentation, of white blood cells, indications, actions, and dosage of, 104 603–604 Hyperstat (diazoxide), indications, Hydrodiuril (hydrochlorothiazide), actions, and dosage of, 526 indications, actions, and dosage of, Hypertension, 392–393 549 algorithm for, 460f Hydromorphone (Dilaudid), indications, Hypertensive crisis, 470 actions, and dosage of, 550 Hypertonic hyponatremia, 185 Hydrothorax, 50 Hypertrophy, on electrocardiogram, 367 5-Hydroxyindoleacetic acid (5-HIAA), in Hyperventilation syndrome, 171 urine, 117 Hypervolemic hypernatremia, 184, 185 Hydroxyurea (Droxia; Hydrea), Hypervolemic hyponatremia, 186 indications, actions, and dosage of, Hypocalcemia, electrocardiogram and, 551 386 Hydroxyzine (Atarax; Vistaril), Hypoglycemia, 471 indications, actions, and dosage of, Hypokalemia, 187–188 551 electrocardiogram and, 385, 386f Hygroton (chlorthalidone), indications, Hypomagnesemia, 190–191 actions, and dosage of, 515 Hyponatremia, 185–186 Hylorel (guanadrel), indications, actions, total parenteral nutrition for, 237 and dosage of, 547 Hypophosphatemia, 192 Hymenolepis nana infections, drugs for total parenteral nutrition for, 236 treating, 154t Hypotonic hyponatremia, 185 Hyoscyamine (Anaspaz; Cystospaz; Hypovolemic hypernatremia, 184 Levsin), indications, actions, and Hypovolemic hyponatremia, 186 dosage of, 551 Hypovolemic shock, 414, 431, 472 Index 697 Hypoxia, 171f, 171–172 Imipramine (Tofranil), indications, differential diagnosis of, 171–172 actions, and dosage of, 552 Hysterosalpingography (HSG), 328 Imipramine + desipramine, half-life and Hytone (hydrocortisone) therapeutic and toxic levels of, indications, actions, and dosage of, 550 633t potency and application of, 629t Imiquimod (Aldara), indications, actions, Hytrin (terazosin), indications, actions, and dosage of, 148t, 552 and dosage of, 608 Imitrex (sumatriptan), indications, actions, and dosage of, 606 Immune globulin, intravenous (Gammar I IV; Gamimmune N; Ibuprofen (Advil; Motrin; Rufen) Sandoglobulin), indications, indications, actions, and dosage of, 551 actions, and dosage of, 552 route, effects, and dosage for, 321t Immune serum globulin, 200t Ibutilide (Corvert) Immune system agents, 484–485 for emergency cardiac care, 464 Immunization schedule, 620, 636t indications, actions, and dosage of, 551 Immunoglobulins, quantitative, laboratory Idarubicin (Idamycin), indications, diagnosis and, 77 actions, and dosage of, 551 Immunomodulators, 484 Ifex (ifosfamide), indications, actions, and Immunosuppressive agents, 485 dosage of, 552 Imodium (loperamide), indications, I125 fibrinogen scanning, 334 actions, and dosage of, 562–563 Ifosfamide (Holoxan; Ifex), indications, Impetigo, organisms responsible and actions, and dosage of, 552 empiric therapy for, 142t Iliopsoas test, 26 Impotence, differential diagnosis of, 48 Ilopan (dexpanthenol) Imuran (azathioprine), indications, indications, actions, and dosage of, 525 actions, and dosage of, 501 in total parenteral nutrition, 231t Inapsine (droperidol), indications, actions, Ilopan-choline Oral (dexpanthenol) and dosage of, 531 indications, actions, and dosage of, 525 Incentive spirometry, 363–364 in total parenteral nutrition, 231t Incidence, definition of, 645 Ilosone (erythromycin), indications, Indapamide (Lozol), indications, actions, actions, and dosage of, 533–534 and dosage of, 552 Ilotycin Ophthalmic (erythromycin, Inderal (propranolol) ophthalmic), indications, actions, for emergency cardiac care, 462 and dosage of, 534 indications, actions, and dosage of, 595 Imaging studies, 325–338 India ink preparation, 127 computed tomography, 330–331 Indinavir (Crixivan), indications, actions, contrast x-ray studies, 326–329 and dosage of, 150t, 553 magnetic resonance, 331–333 Indium-111 octreotide scans, 334 noncontrast x-ray studies, 325–326 Indomethacin (Indocin) nuclear scans, 333–335 indications, actions, and dosage preparation for, 325 of, 553 reading x-rays, 335, 336f, 337f, 338 route, effects, and dosage for, 321t ultrasound, 329–330 Infant formulas and feeding, 223–226, Imdur (isosorbide mononitrate), 224t–225t, 225–226 indications, actions, and dosage of, formulas for, 224t–225t 555–556 initiating, criteria for, 225 Imipenem-cilastin (Primaxin), indications, oral rehydration solutions for, 226 actions, and dosage of, 552 for premature infants, 225t, 225–226 698 Index Infasurf (calfactant), indications, actions, Inhalers, 365 and dosage of, 509 Injection techniques, 276–277 Infections. See also specific infections Innervation, cutaneous, 22f–23f bacterial, 204, 287t Inocor (amrinone) of bone, organisms responsible and for emergency cardiac care, 461 empiric therapy for, 134t indications, actions, and dosage of, 498 cervical, tests for, 291 infusion guidelines for, 439t common, differential diagnosis and Inotropic agents, 480 empiric therapy, 133, 134t–154t, 156t Inspiratory capacity (IC), 416 fungal, systemic drugs for treating, Inspiratory reserve volume (IRV), 416 151t–152t Instrument tie, 357f granulomatous, cerebrospinal fluid in, Insufflation, for sigmoidoscopy, 301 287t Insulins of joints, organisms responsible and comparison of, 622t empiric

therapy for, 134t indications, actions, and dosage of, 553 of skin, organisms responsible and in total parenteral nutrition, 232, 232t empiric therapy for, 141t–142t Intal (cromolyn sodium), indications, of soft tissue, organisms responsible actions, and dosage of, 520–521 and empiric therapy for, 141t–142t Integrilin (eptifibatide) total parenteral nutrition for, 236 for emergency cardiac care, 464 transfusion-associated risk of, 202–204 indications, actions, and dosage of, 533 urinary tract, organisms responsible and Intensive care unit (ICU) empiric therapy for, 143t–144t drug infusions used in, 439t–443t vaginal, 144t–145t, 291 equations used in, 437t–438t viral, 146t–149t, 287t. See also specific progress notes for, 389–391 infections Interferon alfa-2a (Roferon-A), Infectious mononucleosis, 146t indications and dosage for, 146t, Infed (iron dextran), indications, actions, 554 and dosage of, 555 Interferon alfa-2b (Intron A), indications Infergen (interferon alfacon-1), and dosage for, 146t, 148t, 554 indications, actions, and dosage of, Interferon alfa-2B + ribavirin combination 147t, 554 (Robetron), indications, actions, Infiltrates, in lungs, 338 and dosage of, 554 Inflammatory arthritis, synovial fluid Interferon alfacon-1 (Infergen), interpretation and, 250, 251t indications, actions, and dosage of, Inflammatory bowel disease (IBD), total 147t, 554 parenteral nutrition formulation Interferon ß-1B (Betaseron), indications, for, 235 actions, and dosage of, 554 Infliximab (Remicade), indications, Interferon gamma-1B (Actimmune), actions, and dosage of, 553 indications, actions, and dosage of, Influenza A virus, drugs of choice for 554 treating infections by, 147t–148t Intern(s), 1 Influenza B virus, drugs of choice for Internal fetal scalp monitoring, 275–276 treating infections by, 147t Intestinal decompression tubes, 272 Influenza vaccine (Fluogen; Flushield; Intracranial pressure (ICP), derivation and Fluvirin; Fluzone), indications, normal values for, 438t actions, and dosage of, 553 Intradermal injections, 276, 277 Informed consent, 240 Intramuscular injections, 276, 277 INH (isoniazid), indications, actions, and Intrauterine pressure monitoring, 277–278 dosage of, 555–556 Intravascular hemolysis, acute, 202 Index 699 Intravenous (IV) fluids, 179–183 Isoniazid (INH), indications, actions, and maintenance fluids, 179, 181t dosage of, 555–556 specific replacement fluids, 179, Isoosmolar infant formulas, 224t, 225t 182f–183f, 183 Isoproterenol (Isuprel; Medihaler-Iso) Intravenous (IV) infusions, rate for emergency cardiac care, 464 determination for, 183–184 indications, actions, and dosage of, Intravenous pyelography (IVP), 328 398t, 555–556 Intravenous techniques, 278–280, 279f–281f infusion guidelines for, 441t Intraventricular septum rupture, 394 Isoptin (verapamil) Intron A (interferon alfa-2b), indications for emergency cardiac care, 467 and dosage for, 146t, 148t, 554 indications, actions, and dosage of, 617 Intropin (dopamine) Isosorbide dinitrate (Isordil; Sorbitrate), for emergency cardiac care, 462 indications, actions, and dosage of, indications, actions, and dosage of, 555–556 398t, 530 Isosorbide mononitrate (Imdur; Ismo), infusion guidelines for, 440t indications, actions, and dosage of, Iodine-125 fibrinogen scanning, 334 555–556 Iodipine (apraclonidine), indications, Isosporiasis infections, drugs for treating, actions, and dosage of, 499 153t Iodoquinol, indications for, 153t Isotonic hyponatremia, 185 Ionic contrast media, 327 Isotretinoin [13-cis retinoic acid] Iotronex (alosetran), indications, actions, (Accutane), indications, actions, and dosage of, 491 and dosage of, 555–556 Ipecac syrup, indications, actions, and Isovolemic hypernatremia, 184–185 dosage of, 554–555 Isovolemic hyponatremia, 186 Ipratropium bromide (Atrovent), 364 Isradipine (Dynacirc), indications, actions, for asthmatic attacks, 469 and dosage of, 555–556 indications, actions, and dosage of, 555 Isuprel (isoproterenol) Irbesartan (Avapro), indications, actions, for emergency cardiac care, 464 and dosage of, 555 indications, actions, and dosage of, Irinotecan (Camptosar), indications, 398t, 555–556 actions, and dosage of, 555 infusion guidelines for, 441t Iron Itraconazole (Sporanox), indications, actions, laboratory diagnosis and, 77 and dosage of, 151t, 556–557 in total parenteral nutrition, 231 Ivermectin, indications for, 153t, 154t Iron-binding capacity, total (TIBC), laboratory diagnosis and, 78 J Iron dextran (Dexferrum; Infed), Janeway’s lesion, 25 indications, actions, and dosage of, Jaundice, differential diagnosis of, 49 555 Jenest-28, 624t Irradiation blood components, 194 Joffroy’s reflex, 25 Ismelin (guanethidine), indications, Joint infections, organisms responsible actions, and dosage of, 547 and empiric therapy for, 134t Ismo (isosorbide mononitrate), Jugular venous distention, 391–392 indications, actions, and dosage of, 555–556 Isoetharine, indications, actions, and K dosage of, 555 Kabikinase (streptokinase) Isolation protocols, 155–156 for emergency cardiac care, 466 Isomil, 224t indications, actions, and dosage of, 604 700 Index Kaochlor (potassium supplements) Keratoconjunctivitis, herpes simplex virus, form and dosage of, 626t drugs of choice for treating, 147t indications, actions, and dosage of, 592 Kerley’s B lines, 338 Kaochlor 10% (potassium chloride) Kerlone (betaxolol), indications, actions, form and dosage of, 626t and dosage of, 504 indications, actions, and dosage of, 592 Kernig’s sign, 25 Kaochlor Eff (potassium chloride, Ketoconazole (Nizoral), indications, potassium citrate, and actions, and dosage of, 557 bicarbonate), form and dosage of, 17-Ketogenic steroids (17-KGS), in urine, 626t 118 Kaochlor S-F 10% (potassium chloride) Ketone(s), in urine, 111 form and dosage of, 626t Ketone bodies, laboratory diagnosis and, indications, actions, and dosage of, 592 55 Kaolin-pectin (Kaodene; Kao-spen; Ketoprofen (Orudis; Oruvail), indications, Kapectolin), indications, actions, actions, and dosage of, 557 and dosage of, 557 Ketorolac (Toradol), indications, actions, Kaon (potassium gluconate) and dosage of, 557 form and dosage of, 626t Ketorolac, ophthalmic (Acular), indications, actions, and dosage of, 592 indications, actions, and dosage of, Kaon-Cl (potassium chloride) 557 form and dosage of, 626t 17-Ketosteroids (17-KS), total, in urine, indications, actions, and dosage of, 592 118 Kaon-Cl 20% (potassium chloride) Kidney cancer, staging of, 652–653 form and dosage of, 626t Kilogram/pound conversion, 658, 658t indications, actions, and dosage of, 592 Kinase, laboratory diagnosis and, 65 Kaon elixir (potassium gluconate), form Kinyoun stain, 121 and dosage of, 626t Klebsiella, Gram stain characteristics of, Kao-spen (kaolin-pectin), indications, 124f, 126t actions, and dosage of, 557 Klonopin (clonazepam), indications, Kapectolin (kaolin-pectin), indications, actions, and dosage of, 518 actions, and dosage of, 557 K-Lor (potassium chloride) Kayexalate (sodium polystyrene form and dosage of, 626t sulfonate) indications, actions, and dosage of, 592 for hyperkalemia, 187 Klorvess (potassium chloride) indications, actions, and dosage of, 602 form and dosage of, 626t Kayser-Fleischer rings, 25 indications, actions, and dosage of, 592 Kefzol (cefazolin) Klotrix (potassium chloride) indications, actions, and dosage form and dosage of, 626t of, 511 indications, actions, and dosage of, 592 for subacute bacterial endocarditis Knee, arthrocentesis of, 248, 248f prophylaxis, 158t KOH preparation, 127 Kehr’s sign, 25 Koplik’s spots, 25 Keloids, 21t Korotkoff’s sounds, 25 Kemadrin (procyclidine), indications, K-Phos (potassium phosphate), for actions, and dosage of, 594 hypophosphatemia, 192 Kenalog (triamcinolone acetonide), K-Tab (potassium chloride) potency and application of, 630t form and dosage of, 626t Keogh tubes, 273 indications, actions, and dosage of, 592 Keppra (levetiractam), indications, KUB x-rays, 326 actions, and dosage of, 560 Kussmaul’s respirations, 25 Index 701 Kussmaul’s sign, 25 Lamivudine (Epivir; Epivir-HBV), Kwell (lindane), indications, actions, and indications, actions, and dosage of, dosage of, 561 146t, 558 Kyphosis, 26 Lamotrigine (Lamictal), indications, Kytril (granisetron), indications, actions, actions, and dosage of, 558 and dosage of, 546 Lamprene (clofazimine), indications, actions, and dosage of, 518 Lanorinal (aspirin + butalbital compound), L indications, actions, and dosage of, Labetalol (Normodyne; Trandate) 500 for emergency cardiac care, 462 Lanoxicaps (digoxin) for hypertensive crisis, 470 antidote for, 471 indications, actions, and dosage of, 557 for emergency cardiac care, 462 infusion guidelines for, 441t half-life and therapeutic and toxic levels Laboratory diagnosis of, 633t chemistry, immunology, and serology indications, actions, and dosage of, 527 in, 53–93 Lanoxin (digoxin) hematology and, 95–108 antidote for, 471 urine studies for, 109–119 for emergency cardiac care, 462 Laboratory studies. See also specific half-life and therapeutic and toxic levels studies of, 633t before initiating total parenteral indications, actions, and dosage of, 527 nutrition, 233 Lansoprazole (Prevacid), indications, for monitoring total parenteral nutrition, actions, and dosage of, 558 234 Lantus (insulin glorgine), onset, peak, and shorthand for values and, 40f duration of effect of, 622t Lactate dehydrogenase (LD; LDH) Large cells, 97, 100 isozymes of, laboratory diagnosis and, Larva migrans 78 cutaneous, drugs for treating, 153t laboratory diagnosis and, 78 visceral, drugs for treating, 154t Lactic acid, laboratory diagnosis and, 78 Laryngoscopes, 269, 270f Lactic acid + ammonium hydroxide Lasegue’s sign, 26 [ammonium lactate], indications, Lasix (furosemide) actions, and dosage of, 558 for emergency cardiac care, 462–463 Lactinex Granules (lactobacillus), indications, actions, and dosage of, 543 indications, actions, and dosage of, for renal tubular acidosis, 168t 558 Latanoprost (Xalatan), indications, Lactobacillus, Gram stain characteristics actions, and dosage of, 558 of, 126t Late decelerations, in fetal heart rate, Lactobacillus (Lactinex Granules), 276 indications, actions, and dosage of, Lateral chest films, reading, 337f, 338 558 Lateral decubitus chest x-rays, 325 Lactose-free diet, 208t Latex allergy, 344 Lactulose (Cephulac; Chronulac), Laxatives, 483 indications, actions, and dosage of, LCTATE, laboratory diagnosis and, 78 558 Lead, blood, laboratory diagnosis and, 79 Lamictal (lamotrigine), indications, Leads, for electrocardiography, 368 actions, and dosage of, 558 Lee-White clotting time, 107 Lamisil (terbinafine), indications, actions, Leflunomide (Arava), indications, actions, and dosage of, 608 and dosage of, 559 702 Index Left atrial enlargement (LAE), Levetiractam (Keppra), indications, electrocardiogram and, 380, 382f actions, and dosage of, 560 Left bundle branch block (LBBB), 379, Levine’s sign, 26 381f Levin tubes, 272 Left shift, 100 Levobunolol (A-K Beta; Betagan), Left ventricular end-diastolic pressure indications, actions, and dosage of, (LVEDP), 407–408 560 Left ventricular hypertrophy (LVH), Levocabastine (Livostin), indications, electrocardiogram and, 382–383, actions, and dosage of, 560 383f Levo-Dromoran (levorphanol), Legionella antibody, laboratory diagnosis indications, actions, and dosage of, and, 79 560 Legionella pneumophila, Gram stain Levofloxacin (Levaquin), indications, characteristics of, 126t actions, and dosage of, 560 Lente Iletin II, onset, peak, and duration Levonorgestrel implant (Norplant), of effect of, 622t indications, actions, and dosage of, Leonard tubes, 273 560 Lepirudin (Refludan), indications, actions, Levophed (norepinephrine) and dosage of, 559 actions of, 398t Leptocytes, 104 for emergency cardiac care, 466 Lescol (fluvastatin), indications, actions, indications, actions, and dosage and dosage of, 542 of, 580 Letrozole (Femara), indications, actions, infusion guidelines for, 442t and dosage of, 559 Levora 21, 28, 623t Leucovorin (Wellcovorin), indications, Levorphanol (Levo-Dromoran), actions, and dosage of, 559 indications, actions, and dosage of, Leukapheresis, 194 560 Leukeran (chlorambucil), indications, Levothyroxine (Synthroid), indications, actions, and dosage of, 514 actions, and dosage of, 560–561 Leukine (sargramostim), indications, Levsin (hyoscyamine), indications, actions, and dosage of, 600 actions, and dosage of, 551 Leukocyte alkaline phosphatase (LAP) Lhermitte’s sign, 26 score/stain, laboratory diagnosis Librium (chlordiazepoxide), indications, and, 78 actions, and dosage of, 515 Leukocyte esterase, in urine, 112 Lice, drugs for treating, 153t Leukocyte-poor (reduced) red cells, 197t Lichenification, 21t Leuprolide (Lupron), indications, actions, Lidex (fluocinonide), potency and and dosage of, 559 application of, 629t Leustatin (cladribine), indications, actions, Lidex-E (fluocinonide), potency and and dosage of, 517 application of, 629t Levalbuterol (Xopenex), indications, Lidocaine (Anestacon Topical; Xylocaine) actions, and dosage of, 559 for emergency cardiac care, 465 Levamisole (Ergamisol), indications, half-life and therapeutic and toxic levels actions, and dosage of, 560 of, 633t Levaquin (levofloxacin), indications, indications, actions, and dosage actions, and dosage of, 560 of, 561 Levatol (penbutolol), indications, actions, infusion guidelines for, 441t and dosage of, 585 for premature ventricular contractions, Levelen 21, 28, 623t 376 Levelite 21, 28, 623t for suturing, 348, 349t Index 703 Lidocaine + prilocaine (EMLA), Local anesthetics indications, actions, and dosage of, for suturing, 348, 349t 561 systemic, 320 Limb electrodes, 267 Locoid (hydrocortisone butyrate), potency Lindane (Kwell), indications, actions, and and application of, 629t dosage of, 561 Lodine (etodolac), indications, actions, Line sepsis, 435 and dosage of, 536–537 Linezolid (Xyvox), indications, actions, Lodoxamide (Alomide Ophthalmic), and dosage of, 561 indications, actions, and dosage of, Linolenic acid, 233 562 Linton tubes, 273 Löffler methylene blue stain, 128 Lioresal (baclofen), indications, actions, Lomefloxacin (Maxaquin), indications, and dosage of, 502 actions, and dosage of, 562 Liothyronine (Cytomel), indications, Lomotil (diphenoxylate + atropine), actions, and dosage of, 562 indications, actions, and dosage of, Lipase, laboratory diagnosis and, 79 528 Lipid emulsions, 232–233 Lomustine (CCNU; CeeNu), indications, Lipid-lowering agents, 480 actions, and dosage of, 562 Lipid profile, laboratory diagnosis and, 79, Loniten (minoxidil), indications, actions, 80f, 81t and dosage of, 572 Lipitor (atorvastatin), indications, actions, Lo/Ovral, 623t and dosage of, 500 Loperamide (Imodium), indications, Lipoprotein profile/analysis, laboratory actions, and dosage of, 562–563 diagnosis and, 79, 80f, 81t Lopid (gemfibrozil), indications, actions, Liqui-Char (activated charcoal) and dosage of, 544 clinical use of, 472 Lopressor (metoprolol) indications, actions, and dosage of, 514 for emergency cardiac care, 462 Liquid diets, 206t–207t indications, actions, and dosage Lisinopril (Prinivil; Zestril) of, 569 for emergency cardiac care, 461 Loprox (ciclopirox), indications, actions, indications, actions, and dosage of, 562 and dosage of, 516 List, definition of, 26 Lopurin (allopurinol), indications, actions, Listeria, Gram stain characteristics of, and dosage of, 491 123f Loracarbef (Lorabid), indications, actions, Listeria monocytogenes, Gram stain and dosage of, 563 characteristics

of, 126t Loratadine (Claritin), indications, actions, Lithium, half-life and therapeutic and and dosage of, 563 toxic levels of, 633t Lorazepam (Ativan) Lithium carbonate (Eskalith), indications, indications, actions, and dosage of, 563 actions, and dosage of, 562 for seizures, 472 Liver disease Lorcet (hydrocodone + acetaminophen), diet for, 208t indications, actions, and dosage of, total parenteral nutrition formulation 549 for, 235 Lordosis, 26 Liver function tests, elevated, total Lordotic chest x-rays, 325 parenteral nutrition for, 237 Lortab ASA (hydrocodone + aspirin), Liver-spleen scans, 334 indications, actions, and dosage of, Livostin (levocabastine), indications, 549 actions, and dosage of, 560 Losartan (Cozaar), indications, actions, Loa loa, drugs for treating, 153t and dosage of, 563 704 Index Lotensin (benazepril), indications, actions, Luvox (fluvoxamine), indications, actions, and dosage of, 503 and dosage of, 542 Lotrimin (clotrimazole), indications, Lyme disease actions, and dosage of, 519 characteristics and treatment of, Lotrisone (clotrimazole + betamethasone), 156t–157t indications, actions, and dosage of, serology in, laboratory diagnosis and, 519 82 Louvel’s sign, 26 Lyme disease vaccine (Lymerix), Lovastatin (Mevacor), indications, actions, indications, actions, and dosage of, and dosage of, 563 563–564 Lovenox (enoxaparin), indications, Lymphadenopathy, differential diagnosis actions, and dosage of, 532 of, 49 Low-fiber diet, 207t Lymphangiography, 328 Low lactose diet, 208t Lymphocytes Low-Ogestrel, 623t atypical, laboratory diagnosis and, 102 Low osmolality infant formulas, 224t laboratory diagnosis and, 101–102 Lowsium (magaldrate), indications, subsets of, laboratory diagnosis and, actions, and dosage of, 564 103–104 Low-sodium diet, 208t Lymphogranuloma venereum, organism Lozol (indapamide), indications, actions, responsible and empiric therapy and dosage of, 552 for, 135t L-PAM (melphalan), indications, actions, Lymphoma, staging of, 654 and dosage of, 566 Lysodren (mitotane), indications, actions, Ludiomil (maprotiline), indications, and dosage of, 572 actions, and dosage of, 564 Lumbar cistern, 282 Lumbar puncture, 280, 282–286 M complications of, 286 Maalox (aluminum hydroxide + contraindications to, 282 magnesium hydroxide), historical background of, 282–283, 283f indications, actions, and dosage of, indications for, 280 493–494 materials for, 282 McBurney’s point/sign, 26 technique for, 284, 285f, 286, McGill Pain Questionnaire (MPQ), 319 287t–288t McMurray’s test, 26 Lumens, of Swan-Ganz catheters, Macrodantin (nitrofurantoin), indications, 399–400 actions, and dosage of, 579 Lung(s), on chest x-rays, 335, 336f, 337f, Macrolides, 477 338 Macules, 21t Lung cancer, staging of, 653–654 MAG3 (technetium-99m Lung capacity, 416, 416f, 417f mercaptoacetylthiglycine), 334 Lung compliance, 417–418, 418f Magaldrate (Lowsium; Riopan), Lung scans, 334 indications, actions, and dosage of, Lupron (leuprolide), indications, actions, 564 and dosage of, 559 Magnesium Lupus erythematosus (LE) preparation, deficiency of, 190–191 laboratory diagnosis and, 78 excess of, 190, 237 Luteinizing hormone (LH), serum, laboratory diagnosis and, 82 laboratory diagnosis and, 79, 82 requirement for, 178 Lutrepulse (gonadorelin), indications, total parenteral nutrition for excess of, actions, and dosage of, 546 237 Index 705 Magnesium citrate, indications, actions, Matulane (procarbazine), indications, and dosage of, 564 actions, and dosage of, 593–594 Magnesium hydroxide (Milk of Mavik (trandolapril), indications, actions, Magnesia), indications, actions, and dosage of, 613 and dosage of, 564 Maxair (pirbuterol), indications, actions, Magnesium oxide (Mag-Ox 400) and dosage of, 590 for hypomagnesemia, 191 Maxalt (rizatriptan), indications, actions, indications, actions, and dosage of, 564 and dosage of, 599 Magnesium sulfate Maxaquin (lomefloxacin), indications, for emergency cardiac care, 465 actions, and dosage of, 562 for hypomagnesemia, 191 Maxipime (cefepime), indications, indications, actions, and dosage of, 564 actions, and dosage of, 511 Magnetic resonance imaging (MRI), Maxitrol (neomycin, polymyxin B, + 331–333 dexamethasone), indications, reading, 331–332 actions, and dosage of, 577 uses of, 332–333 Maxon (polyglyconate) sutures, 346t Magnetic resonance spectroscopy (MRS), Maxzide (hydrochlorothiazide + 332–333 triamterene), indications, actions, Mag-Ox 400 (magnesium oxide) and dosage of, 549 for hypomagnesemia, 191 Mean arterial blood pressure (MAP), 393, indications, actions, and dosage of, 564 394f Malaria derivation and normal values for, 437t drugs for treating, 153t Mean cellular (corpuscular) hemoglobin prevention of, 153t (MCH), laboratory diagnosis and, Malathion, indications for, 153t 102 Malignancies Mean cell (corpuscular) volume (MCV), classification systems for, 646, 649–658 laboratory diagnosis and, 102 hypercalcemia with, 188 Mean pulmonary arterial pressure Malnutrition, identification of, 209, (MPAP), derivation and normal 210t–212t values for, 437t Mammography, 326 Measles virus, drug of choice for treating Manganese, in total parenteral nutrition, infections by, 148t 231, 232t Measurement units, 645–646 Mannitol Mebendazole, indications for, 153t for emergency cardiac care, 465 Mechanical soft diet, 206t indications, actions, and dosage Mechanical ventilation, 423–429 of, 564 extubation and, 428–429 Mantoux test, 303–304 indications for, 423, 424t Maprotiline (Ludiomil), indications, orders for, 426 actions, and dosage of, 564 ventilator classes for, 423–424 Marcaine (bupivacaine) ventilator modes for, 424, 425f, 426 indications, actions, and dosage of, 507 ventilator setting changes for, 426–427 for suturing, 349t weaning from, 427–429, 428t Marcus-Gunn pupils, 26 Mechlorethamine (Mustargen), Marinol (dronabinol), indications, actions, indications, actions, and dosage of, and dosage of, 531 564 Mastitis, organism responsible and Meclizine (Antivert), indications, actions, empiric therapy for, 134t and dosage of, 564 Mastoiditis, organisms responsible and Mediastinal computed tomography, 331 empiric therapy for, 135t Mediastinum, on chest x-rays, 335 706 Index Medical history, 9–10 Meridia (sibutramine), indications, Medigesic (acetaminophen + butalbital +/- actions, and dosage of, 601 caffeine), indications, actions, and Meropenem (Merrem), indications, dosage of, 489 actions, and dosage of, 566 Medihaler-Iso (isoproterenol) Mesalamine (Asacol; Pentasa; Rowasa), for emergency cardiac care, 464 indications, actions, and dosage of, indications, actions, and dosage of, 566 398t, 555–556 Mesna (Mesnex), indications, actions, and infusion guidelines for, 441t dosage of, 567 Mediquell (dextromethorphan), Mesoridazine (Serentil), indications, indications, actions, and dosage of, actions, and dosage of, 567 525 Metabolic acidosis, 164t, 166–167 Medroxyprogesterone (Cycrin; Depo differential diagnosis of, 17B, 167f, Provera; Provera), indications, 168t actions, and dosage of, 564 treatment of, 167 Medulla, herniation of, with lumbar Metabolic alkalosis, 164t, 167, 169 puncture, 286 differential diagnosis of, 167, 169, 169f Mefaxin (cefoxitin), indications, actions, total parenteral nutrition for, 237 and dosage of, 512 treatment of, 169 Mefloquine, indications for, 153t Metamucil (psyllium), indications, Megestrol acetate (Megace), indications, actions, and dosage of, 596 actions, and dosage of, 564 Metanephrines, in urine, 117 Melanoma, staging of, 654–655 Metaproterenol (Alupent; Metaprel), 364 Melena, differential diagnosis of, 47 indications, actions, and dosage of, 567 Mellaril (thioridazine), indications, Metaraminol (Aramine), indications, actions, and dosage of, 609–610 actions, and dosage of, 567 Meloxicam (Mobic), indications, actions, Metastron, 334 and dosage of, 564 Metaxalone (Skelaxin), indications, Melphalan (Alkeran; L-PAM), indications, actions, and dosage of, 567 actions, and dosage of, 566 Metered-dose inhalers, 365 Menest (estrogens, esterified), indications, Metformin (Glucophage), indications, actions, and dosage of, 535 actions, and dosage of, 567 Meningitis Methadone (Dolophine) aseptic, cerebrospinal fluid in, 287t indications, actions, and dosage of, organisms responsible and empiric 567–568 therapy for, 138t–139t route, effects, and dosage for, 321t Meperidine (Demerol) Methanol, antidote for, 471 indications, actions, and dosage Methenamine (Hiprex; Urex), indications, of, 566 actions, and dosage of, 568 route, effects, and dosage for, 321t Methergine (methylergonovine), Mepivacaine (Carbocaine), for suturing, indications, actions, and dosage of, 349t 569 Meprobamate (Equanil; Miltown), Methimazole (Tapazole), indications, indications, actions, and dosage of, actions, and dosage of, 568 566 Methocarbamol (Robaxin), indications, Mepron (atovaquone), indications, actions, actions, and dosage of, 568 and dosage of, 500–501 Methotrexate (Folex; Rheumatrex) Mercaptopurine [6-MP] (Purinethol), half-life and therapeutic and toxic levels indications, actions, and dosage of, of, 633t 566 indications, actions, and dosage of, 568 Index 707 Methoxamine (Vasoxyl), indications, Micardis (telmisartan), indications, actions, and dosage of, 568–569 actions, and dosage of, 607 Methyldopa (Aldomet), indications, Miconazole (Monistat), indications, actions, and dosage of, 569 actions, and dosage of, 571 Methylergonovine (Methergine), Microalbumin, spot urine study for, 115 indications, actions, and dosage of, Microbiology, 121–159 569 blood cultures, 129–130 Methylprednisolone differential diagnosis of common for anaphylaxis, 469 infections and empiric therapy, 133, for asthmatic attacks, 469 134t–154t, 156t indications, actions, and dosage of, 603 gonorrhea cultures and smear, 129 Methylprednisolone acetate (Depo- isolation protocols, 155–156 Medrol) molecular, 132 dose, activity, duration, and route for, nasopharyngeal cultures, 129 627t SBE prophylaxis, 155, 158t–159t indications, actions, and dosage of, 603 Scotch tape test, 132 Methylprednisolone sodium succinate sputum culture, 130 (Solu-Medrol) staining techniques for, 121–128 dose, activity, duration, and route for, stool cultures, 130–131 627t susceptibility testing, 133 indications, actions, and dosage of, 603 throat cultures, 131 Metoclopramide (Clopra; Octamide; urine cultures, 131–132 Reglan), indications, actions, and viral cultures and serology, 132 dosage of, 569 β2-Microglobulin Metolazone (Diulo; Zaroxolyn), laboratory diagnosis and, 82 indications, actions, and dosage of, spot urine study for, 114 569 Microhemagglutination, Treponema Metopirone (metyrapone), indications, pallidum (MHA-TP), laboratory actions, and dosage of, 570 diagnosis and, 82 Metoprolol (Lopressor; Toprol XL) Micro-K (potassium chloride) for emergency cardiac care, 462 form and dosage of, 626t indications, actions, and dosage indications, actions, and dosage of, 592 of, 569 Micronase (glyburide), indications, Metronidazole (Flagyl; Metrogel), actions, and dosage of, 545 indications, actions, and dosage of, Micronor, 625t 153t, 154t, 570 Midamor (amiloride), indications, actions, Metyrapone (Metopirone), indications, and dosage of, 494 actions, and dosage of, 570 Midazolam (Versed) Metyrosine (Demser), indications, actions, indications, actions, and dosage of, 571 and dosage of, 570 for seizures, 472 Mevacor (lovastatin), indications, actions, Middle cells, 97, 100 and dosage of, 563 Mifepristone [RU 486] (Mifeprex), Mexiletine (Mexitil), indications, actions, indications, actions, and dosage of, and dosage of, 570 571 Mezlocillin (Mezlin), indications, actions, Miglitol (Glyset), indications, actions, and and dosage of, 570 dosage of, 571 Miacalcin (calcitonin) Migraine headache agents, 486 for hypercalcemia, 189 Milk of Magnesia (magnesium indications, actions, and dosage of, 508 hydroxide), indications, actions, MIBG, 333 and dosage of, 564 708 Index Miller-Abbott tubes, 272 Mobitz type II heart block, 378 Milrinone (Primacor), indications, actions, Möbius’ sign, 26 and dosage of, 571 Modicon 28, 623t Miltown (meprobamate), indications, Moduretic (hydrochlorothiazide + actions, and dosage of, 566 amiloride), indications, actions, Mineral oil, indications, actions, and and dosage of, 549 dosage of, 571 Moexipril (Univasc), indications, actions, Mini mental status examination, 13–14, and dosage of, 573 15t Molecular microbiology, 132 Minimum bactericidal concentration Molindone (Moban), indications, actions, (MBC), 133 and dosage of, 573 Minimum inhibitory concentration (MIC), Mometasone furoate (Elocon), potency 133 and application of, 630t Minipress (prazosin), indications, actions, Monistat (miconazole), indications, and dosage of, 593 actions, and dosage of, 571 Minnesota tubes, 273 Monocid (cefonicid), indications, actions, Minoxidil (Loniten; Rogaine), indications, and dosage of, 511–512 actions, and dosage of, 572 Monoclate (antihemophilic factor) Mirapex (pramipexole), indications, indications, actions, and dosage of, 498 actions, and dosage of, 592 for transfusion, 199t Mircette 28, 624t Monocryl (poliglecaprone) sutures, 346t Mirtazapine (Remeron), indications, Monocytes, laboratory diagnosis and, actions, and dosage of, 572 102–103 Misoprostol (Cytotec), indications, Monopril (fosinopril), indications, actions, actions, and dosage of, 572 and dosage of, 543 Mithracin (plicamycin) Monospot, laboratory diagnosis and, 83 for hypercalcemia, 189 Montelukast (Singulair), indications, indications, actions, and dosage of, actions, and dosage of, 573 590–591 Monurol (fosfomycin), indications, Mitomycin C (Mutamycin), indications, actions, and dosage of, 542–543 actions, and dosage of, 572 Moraxella catarrhalis, Gram stain Mitotane (Lysodren), indications, actions, characteristics of, 125t and dosage of, 572 Morganella morganii, Gram stain Mitotic inhibitors, 478 characteristics of, 126t Mitoxantrone (Novantrone), indications, Moricizine (Ethmozine), indications, actions, and dosage of, 572–573 actions, and dosage of, 573 Mitral insufficiency (MI), 16t Morning rounds, 3 Mitral stenosis (MS), 16t Moro’s reflex, 26 Mivacurium (Mivacron), indications, Morphine (Duramorph; MS Contin; actions, and dosage of, 573 Roxanol) Mixed acid-base disorders, 163 for emergency cardiac care, 465 Mixed venous oxygen content (CVO2), indications, actions, and dosage of, 573 derivation and normal values for, route, effects, and dosage for, 321t 437t Motrin (Ibuprofen) M-mode echocardiography, 330 indications, actions, and dosage of, 551 Moban (molindone), indications, actions, route, effects, and dosage for, 321t and dosage of, 573 Moxifloxacin (Avelox), indications, Mobic (meloxicam), indications, actions, actions, and dosage of, 574 and dosage of, 564 MS Contin (morphine) Mobitz type I heart block, 377–378, 379f for emergency cardiac care, 465 Index 709 indications, actions, and dosage Mycostatin (nystatin), indications, actions, of, 573 and dosage of, 580 route, effects, and dosage for, 321t Myelography, 329 Mucomyst (acetylcysteine), 364 Myleran (busulfan), indications, actions, indications, actions, and dosage of, and dosage of, 507 489–490 Mylicon (simethicone), indications, Mucormycosis, systemic drug for treating, actions, and dosage of, 601 152t Myocardial infarction (MI) Mucosil (acetylcysteine), 364 anticoagulant standard of practice for, indications, actions, and dosage of, 637t 489–490 on electrocardiograms, 367, 383f–385f, Mucus, in urine sediment, 114 383–384, 385t MUGA scans, 333–334 Myocardial ischemia Multifocal atrial tachycardia (MAT), 373, on electrocardiogram, 367 374f electrocardiogram and, 383f–385f, 384 Multiple sclerosis, cerebrospinal fluid in, Myoglobin 288t laboratory diagnosis and, 83 Mupirocin

(Bactroban), indications, spot urine study for, 115 actions, and dosage of, 574 Muromonab-CD3 (Orthoclone OKT3), indications, actions, and dosage of, 574 N Murphy’s sign, 26 Nabumetone (Relafen), indications, Muscle relaxants, 485 actions, and dosage of, 574 Musculoskeletal agents, 485 Nadolol (Corgard), indications, actions, Musculoskeletal magnetic resonance and dosage of, 574 imaging, 333 Nafcillin (Nallpen), indications, actions, Muse (alprostadil, urethral suppository), and dosage of, 574 indications, actions, and dosage of, Naftifine (Naftin), indications, actions, 492 and dosage of, 574 Musset’s sign, 26 Nalbuphine (Nubain) Mustargen (mechlorethamine), indications, actions, and dosage of, 575 indications, actions, and dosage of, route, effects, and dosage for, 322t 564 Nalfon (fenoprofen), indications, actions, Mutamycin (mitomycin C), indications, and dosage of, 537–538 actions, and dosage of, 572 Nalidixic acid (Neggram), indications, Myambutol (ethambutol), indications, actions, and dosage of, 575 actions, and dosage of, 536 Nallpen (nafcillin), indications, actions, Mycelex (clotrimazole), indications, and dosage of, 574 actions, and dosage of, 519 Naloxone (Narcan) Mycobacterium, Gram stain for emergency cardiac care, 465 characteristics of, 126t indications, actions, and dosage Mycobutin (rifabutin), indications, of, 575 actions, and dosage of, 598 for opiate overdose, 471 Mycolog-II (triamcinolone + nystatin), Naltrexone (Revia), indications, actions, indications, actions, and dosage of, and dosage of, 575 613 Napamide (disopyramide) Mycophenolate mofetil (Cellcept), half-life and therapeutic and toxic levels indications, actions, and dosage of, of, 633t 574 indications, actions, and dosage of, 529 710 Index Naphazoline + antazoline (Albalon-A Nebupent (pentamidine), indications, Ophthalmic), indications, actions, actions, and dosage of, 153t, 585 and dosage of, 575 Necator americanus infections, drugs for Naphazoline + pheniramine acetate treating, 153t (Naphcon A), indications, actions, Neck computed tomography, 331 and dosage of, 575 Necon 1/35 21, 28, 623t Naphcon A (naphazoline + pheniramine Necon 1/50 21, 28, 623t acetate), indications, actions, and Necon 10/11 21, 28, 624t dosage of, 575 Necon 0.5/35E 21, 28, 623t Naprosyn (naproxen), indications, actions, Nedocromil (Tilade), indications, actions, and dosage of, 575 and dosage of, 576 Naproxen (Aleve; Anaprox; Naprosyn), Needle(s) indications, actions, and dosage of, French units for, 240, 241f 575 for suturing, 345 Naratriptan (Amerge), indications, actions, Needle cricothyrotomy, 263–264 and dosage of, 575–576 Nefazodone (Serzone), indications, Narcan (naloxone) actions, and dosage of, 576 for emergency cardiac care, 465 Negative nitrogen balance, 229 indications, actions, and dosage of, 575 Neggram (nalidixic acid), indications, for opiate overdose, 471 actions, and dosage of, 575 Narcotics, 486 Neisseria gonorrhoeae analgesics, 320, 321t–322t Gram stain characteristics of, 124f, 125t overdose of, 471 throat culture for, 131 Nardil (phenelzine), indications, actions, Neisseria meningitides, Gram stain and dosage of, 588 characteristics of, 124f, 125t Narrow complex SVT algorithm, 457f Nelfinavir (Viracept), indications, actions, Nasalcrom (cromolyn sodium), and dosage of, 150t, 576 indications, actions, and dosage of, Nelova 1/35 21, 623t 520–521 Nelova 1/50 21, 623t Nasogastric intubation Nelova 10/11 21, 624t IV fluid replacement with, 179 Nelova 0.5/35E 21, 623t procedure for, 273–274 Nembutal (pentobarbital), indications, tubes for, 272 actions, and dosage of, 587 Nasolide (flunisolide), indications, Neo-calglucon (calcium glubionate) actions, and dosage of, 540 for hypocalcemia, 190 Nasopharyngeal cultures, 129 indications, actions, and dosage of, 508 Nausea, differential diagnosis of, 49 Neodecadron Ophthalmic (neomycin + Navane (thiothixene), indications, actions, dexamethasone), indications, and dosage of, 610 actions, and dosage of, 576 Navelbine (vinorelbine), indications, Neomycin, colistin, hydrocortisone, + actions, and dosage of, 618 thonzonium (Cortisporin-TC Otic NAVEL mnemonic, 313 Suspension), indications, actions, for arterial puncture, 246 and dosage of, 576 Nebcin (tobramycin) Neomycin, colistin, + hydrocortisone half-life and therapeutic and toxic levels (Cortisporin-TC Otic Drops), of, 631t indications, actions, and dosage of, indications, actions, and dosage of, 611 576 Nebulizer therapy, 363 Neomycin + dexamethasone (AK-NEO- topical medications for, 364 DEX Ophthalmic; Neodecadron Index 711 Ophthalmic), indications, actions, indications, actions, and dosage of, and dosage of, 576 398t, 588–589 Neomycin + polymyxin B (Neosporin infusion guidelines for, 443t Cream), indications, actions, and Nephrostography, percutaneous, 329 dosage of, 576 Nephrotomography, 328 Neomycin, polymyxin B, + Nerve blocks, 320 dexamethasone (Maxitrol), Nerve conduction testing, for pain indications, actions, and dosage of, evaluation, 319 577 Nerve root trauma, with lumbar puncture, Neomycin, polymyxin bladder irrigant, 286 indications, actions, and dosage of, Neumega (oprelvekin), indications, 577 actions, and dosage of, 582 Neomycin, polymyxin, + hydrocortisone Neupogen (filgrastim), indications, (Cortisporin Ophthalmic and Otic), actions, and dosage of, 539 indications, actions, and dosage of, Neural blockade, for pain management, 577 319 Neomycin, polymyxin-B, + prednisolone Neurogenic shock, 414, 431 (Poly-Pred Ophthalmic), Neuroleptics, for pain management, 320 indications, actions, and dosage of, Neurologic examination, 12 577 Neurolysis, 320 Neomycin sulfate, indications, actions, Neuromuscular blockers, 485 and dosage of, 577 Neurontin (gabapentin), indications, Neonatal ophthalmia, organism actions, and dosage of, 543 responsible and empiric therapy Neutra-Phos (sodium-potassium for, 135t phosphate) Neoplasms. See also Malignancies for hypercalcemia, 189 adrenal, differential diagnosis of, 42 for hypophosphatemia, 192 cerebrospinal fluid in, 288t Neutrexin (trimetrexate), indications, classification systems for, 646, 649–658 actions, and dosage of, 615 cutaneous, 21t Neutrophils. See Polymorphonuclear Neoral (cyclosporine) neutrophils (PMNs) half-life and therapeutic and toxic levels Nevirapine (Viramune), indications, of, 634t actions, and dosage of, 577 indications, actions, and dosage of, Niacin (Nicolar) 521–522 indications, actions, and dosage of, 577 Neosar (cyclophosphamide), indications, in total parenteral nutrition, 231t actions, and dosage of, 521 Nicardipine (Cardene) Neosporin Cream (neomycin + polymyxin indications, actions, and dosage of, 578 B), indications, actions, and infusion guidelines for, 441t–442t dosage of, 576 Nicoderm (nicotine, transdermal), Neosporin ointment (bacitracin, indications, actions, and dosage of, neomycin, + polymyxin B, 578 topical), indications, actions, and Nicolar (niacin) dosage of, 502 indications, actions, and dosage of, 577 Neosporin Ophthalmic (bacitracin, in total parenteral nutrition, 231t neomycin, + polymyxin B, Nicorette (nicotine gum), indications, ophthalmic), indications, actions, actions, and dosage of, 578 and dosage of, 502 Nicorette D5 (nicotine gum), indications, Neo-Synephrine (phenylephrine) actions, and dosage of, 578 712 Index Nicotine, transdermal (Habitrol; Nitrogen balance, 229 Nicoderm; Nicotrol; Prostep), Nitrogen mustards, 478 indications, actions, and dosage of, Nitroglycerin (Nitro-Bid IV; Nitro-Bid 578 Ointment; Nitrodisc; Nitrolingual; Nicotine gum (Nicorette; Nicorette D5), Transderm-Nitro) indications, actions, and dosage of, for emergency cardiac care, 465 578 indications, actions, and dosage of, 579 Nicotine nasal spray (Nicotrol NS), Nitroglycerin (Tridil), infusion guidelines indications, actions, and dosage of, for, 442t 578 Nitrolingual (nitroglycerin) Nicotrol (nicotine, transdermal), for emergency cardiac care, 465 indications, actions, and dosage of, indications, actions, and dosage of, 579 578 Nitroprusside (Nipride; Nitropress) Nicotrol NS (nicotine nasal spray), for emergency cardiac care, 465–466 indications, actions, and dosage of, for hypertensive crisis, 470 578 indications, actions, and dosage of, 579 Nifedipine (Adalat; Adalat CC; Procardia; infusion guidelines for, 442t Procardia XL), indications, Nitrosoureas, 478 actions, and dosage of, 578 Nix (permethrin), indications, actions, and Night of surgery notes, 36–37 dosage of, 153t, 154t, 588 Nilandron (nilutamide), indications, Nizatidine (Axid), indications, actions, actions, and dosage of, 578 and dosage of, 579 Nilstat (nystatin), indications, actions, and Nizoral (ketoconazole), indications, dosage of, 580 actions, and dosage of, 557 Nilutamide (Nilandron), indications, Nocardia, Gram stain characteristics of, actions, and dosage of, 578 126t Nimodipine (Nimotop), indications, Nocardiosis, organism responsible and actions, and dosage of, 578–579 empiric therapy for, 139t Nipent (pentostatin), indications, actions, Noctec (chloral hydrate), indications, and dosage of, 587 actions, and dosage of, 514 Nipride (nitroprusside) Nodal rhythm, on electrocardiograms, for emergency cardiac care, 465–466 374–375, 376f for hypertensive crisis, 470 Nodules, cutaneous, 21t indications, actions, and dosage of, 579 Nolvadex (tamoxifen), indications, infusion guidelines for, 442t actions, and dosage of, 606–607 Nisoldipine (Sular), indications, actions, Nonanion gap acidosis, 166, 168t and dosage of, 579 Nonhemolytic febrile reactions, 202, 203 Nitrite, in urine, 111 Noninflammatory arthritis, synovial fluid Nitro-Bid IV (nitroglycerin) interpretation and, 250, 251t for emergency cardiac care, 465 Nonionic contrast media, 327 indications, actions, and dosage of, 579 Nonsteroidal anti-inflammatory agents, Nitro-Bid Ointment (nitroglycerin) 486 for emergency cardiac care, 465 Norcuron (vecuronium), indications, indications, actions, and dosage of, 579 actions, and dosage of, 617 Nitrodisc (nitroglycerin) Nordette-21, 623t for emergency cardiac care, 465 Norepinephrine (Levophed) indications, actions, and dosage of, 579 actions of, 398t Nitrofurantoin (Furadantin Macrobid; for emergency cardiac care, 466 Macrodantin), indications, actions, indications, actions, and dosage of, 580 and dosage of, 579 infusion guidelines for, 442t Index 713 Norflex (orphenadrine), indications, NPH Iletin II, onset, peak, and duration of actions, and dosage of, 582 effect of, 622t Norfloxacin (Noroxin), indications, Nubain (nalbuphine) actions, and dosage of, 580 indications, actions, and dosage of, 575 Norgestrel (Ovrette), 625t route, effects, and dosage for, 322t indications, actions, and dosage of, 580 Nuclear scans, 333–335 Norinyl 1/35 21, 28, 623t Nucleated RBCs, 104 Norinyl 1/50 21, 28, 623t 5′-Nucleotidase, laboratory diagnosis and, Normal compensatory response, 163 83 Normiflo (ardeparin), indications, actions, Numorphan (oxymorphone), indications, and dosage of, 499 actions, and dosage of, 584 Normodyne (labetalol) Nupercainal (dibucaine), indications, for emergency cardiac care, 462 actions, and dosage of, 526 for hypertensive crisis, 470 Nurolong (nylon) sutures, 347t indications, actions, and dosage of, 557 Nursoy, 224t infusion guidelines for, 441t Nutramigen, 224t Noroxin (norfloxacin), indications, Nutrition, 205–226. See also Nutritional actions, and dosage of, 580 support; Total parenteral nutrition Norpace (disopyramide) (TPN) half-life and therapeutic and toxic levels assessment of, 205, 209, 210t–212t of, 633t for critically ill patents, 434 indications, actions, and dosage of, 529 hospital diets and, 205, 206t–208t Norplant (levonorgestrel implant), requirements for, 209, 213 indications, actions, and dosage of, Nutritional support 560 enteral, 213, 214t, 214–223 Norpramin (desipramine) parenteral, 213–214 half-life and therapeutic and toxic levels Nylon (Dermalon; Ethilon) sutures, 346t of, 633t Nylon (Nurolon) sutures, 347t indications, actions, and dosage of, 524 Nystagmus, differential diagnosis of, 49 Nor-QD, 625t Nystatin (Mycostatin; Nilstat), indications, Nortriptyline (Aventyl; Pamelor) actions, and dosage of, 580 half-life and therapeutic and toxic levels of, 633t indications, actions, and dosage O of, 580 Obesity, medication for, 482 Norvasc (amlodipine), indications, Obstetric agents, 485–486 actions, and dosage of, 496 Obstruction series, 326 Norvir (ritonavir), indications, actions, Obturator sign, 26 and dosage of, 150t, 599 Occupress Ophthalmic (carteolol), Novafed (pseudoephedrine), indications, indications, actions, and dosage of, actions, and dosage of, 595–596 510 Novantrone (mitoxantrone), indications, Octamide (metoclopramide), indications, actions, and dosage of, 572–573 actions, and dosage of, 569 Novocain (procaine), for suturing, 349t OctreoScans, 334 NovoLog (insulin aspart), onset, peak, and Octreotide (Sandostatin), indications, duration of effect of, 622t actions, and dosage of, 580–581 Novulin 70/30, onset, peak, and duration Ocuflox Ophthalmic (ofloxacin), of effect of, 622t indications, actions, and dosage of, Novulin L, onset, peak, and duration of 580–581 effect of, 622t Off-service notes, 35 714 Index Ofloxacin (Floxin; Ocuflox Ophthalmic), indications, actions, and dosage of, 582 indications, actions, and dosage of, Oral herpes, drugs of choice for treating, 580–581 147t Olanzapine (Zyprexa), indications, Oral procedures, subacute bacterial actions, and dosage of, 580–581 endocarditis prophylaxis for, 158t Oligoclonal banding, CSF, laboratory Oral supplements, 217 diagnosis and, 83 Orders, 6 Oliguria, 432–433 writing, 33–34 differential diagnosis of, 49–50 Organon (desogen), 623t Olsalazine (Dipentum), indications, Organophosphates, antidote for, 471 actions, and dosage of, 580–581 Orgestrel-28, 624t Omeprazole (Prilosec), indications, Orinase (tolbutamide), indications, actions, and dosage of, 580–581 actions, and dosage of, 612 Omnicef (cefdinir), indications, actions, Orphenadrine (Norflex), indications, and dosage of, 511 actions, and dosage of, 582 Omnipen (ampicillin) Ortho-Cept 21, 624t indications, actions, and dosage Orthoclone OKT3 (muromonab-CD3), of, 497 indications, actions, and dosage of, for subacute bacterial endocarditis 574 prophylaxis, 158t, 159t Ortho-Cyclen 21, 624t Oncovin (vincristine), indications, actions, Ortho-Novum 1/35 21, 624t and dosage of, 617–618 Ortho-Novum 1/50 21, 624t Ondansetron (Zofran), indications, Ortho-Novum 7/7/7 21, 625t actions, and dosage of, 580–581 Ortho-Novum 10/11 21, 624t On-service notes, 35 Orthostatic blood pressure measurement, Operating room, 339–344 286–289 draping patients for, 343 Ortho Tri-Cyclen, 624t entering, 339–340 Ortolani’s test/sign, 26 gowning and gloving for, 342–343 Orudis (ketoprofen), indications, actions, hand scrub for, 340–341 and dosage of, 557 patient preparation for, 341–342 Oruvail (ketoprofen), indications, actions, position in, 343–344 and dosage of, 557 sterile technique for, 339 Oseltamivir (Tamiflu), indications, universal precautions in, 344 actions, and dosage of, 147t, 582 Operative notes, 36 Osler’s nodes, 26 Ophthalmia, neonatal, organism Osmolality responsible and empiric therapy serum, laboratory diagnosis and, 83 for, 135t spot urine study for, 115 Ophthalmic agents, 482–483 Osteomyelitis, organisms responsible and Opioids, 486 empiric therapy for, 134t analgesics, 320, 321t–322t Osteoporosis, medications for, 482 overdose of, 471 Otic agents, 482 Oprelvekin (Neumega), indications, Otic Domeboro (acetic acid + aluminum actions, and dosage of, 582 acetate), indications, actions, and Opticrom (cromolyn sodium), indications, dosage of, 489 actions, and dosage of, 520–521 Otitis externa,

organisms responsible and Oral cholecystography (OCG), 329 empiric therapy for, 135t–136t Oral contraceptives, 485 Otitis media, organisms responsible and composition of, 623t–625t empiric therapy for, 136t Index 715 Otobiotic Otic (polymyxin B + Oxymorphone (Numorphan), indications, hydrocortisone), indications, actions, and dosage of, 584 actions, and dosage of, 590–591 Oxytocin (Pitocin; Syntocinon), Outpatient prescriptions, writing, 37–39, 38f indications, actions, and dosage of, Ova, stool for, 131 584 Ovarian cancer, staging of, 655 Ovral, 624t Ovrette (norgestrel), 625t P indications, actions, and dosage of, 580 Pacerone (amiodarone) Oxacillin (Bactocill; Prostaphlin), for emergency cardiac care, 461 indications, actions, and dosage of, half-life and therapeutic and toxic levels 582–583 of, 632t Oxaprozin (Daypro), indications, actions, indications, actions, and dosage of, 495 and dosage of, 583 Pacing, transcutaneous, 468 Oxazepam (Serax), indications, actions, Pacing Swans, 401 and dosage of, 583 Pacis (BCG [bacillus Calmette-Guérin]), Oxcarbazepine (Trileptal), indications, indications, actions, and dosage of, actions, and dosage of, 583 503 Oxiconazole (Oxistat), indications, Packed red cells (PRBCs), 197t actions, and dosage of, 583 Paclitaxel (Taxol), indications, actions, Oximetric PA catheters, 401 and dosage of, 584 Oxistat (oxiconazole), indications, actions, Pain and dosage of, 583 acute, 315–316 Oxybutynin (Ditropan; Ditropan XL), chronic, 316 indications, actions, and dosage of, differential diagnosis of, 42 583 Pain management, 315–323. See also Oxycodone [dihydrohydroxycodeinone] Analgesics (Oxycontin; OxyIR; Roxicodone), adverse physiologic effects of pain and, indications, actions, and dosage of, 316, 317t–318t 583 classification of pain and, 315–316 Oxycodone + acetaminophen (Percocet; evaluation for, 317 Tylox), indications, actions, and nonpharmacologic, 320, 323 dosage of, 583–584 pain measurement and, 316, 319 Oxycodone + aspirin (Percodan; patient controlled analgesia for, 323 Percodan-Demi), indications, pharmacologic, 319–320, 321t–322t actions, and dosage of, 584 terminology for, 315 Oxycontin (oxycodone), indications, Pamelor (nortriptyline) actions, and dosage of, 583 half-life and therapeutic and toxic levels Oxygen, for carbon monoxide poisoning, of, 633t 471 indications, actions, and dosage of, 580 Oxygenation, 418–423, 420f–422f Pamidronate (Aredia) Oxygen carrying capacity, derivation and for hypercalcemia, 189 normal values for, 437t indications, actions, and dosage of, Oxygen consumption, derivation and 584–585 normal values for, 438t Panacryl sutures, 346t Oxygen delivery, 419 Pancoast’s syndrome, 26 Oxygen supplements, 362t Pancrease (pancreatin + pancrelipase), OxyIR (oxycodone), indications, actions, indications, actions, and dosage of, and dosage of, 583 585 716 Index Pancreatic disease, total parenteral Parlodel (bromocriptine), indications, nutrition formulation for, 235 actions, and dosage of, 506 Pancreatic loss, IV fluid replacement with, Paromomycin, indications for, 153t 179 Paromycin, indications for, 153t Pancreatin + pancrelipase (Cotazyme; Paroxetine (Paxil), indications, actions, Creon; Pancrease; Ultrase), and dosage of, 585 indications, actions, and dosage of, Paroxysmal atrial tachycardia (PAT), 585 372–373, 374f Pancuronium (Pavulon), indications, Partial thromboplastin time (PTT), 107 actions, and dosage of, 585 Pasteurella, Gram stain characteristics of, P-24 antigen, laboratory diagnosis and, 124f 77, 83 Pastia’s lines, 26 Pantoprazole (Protonix), indications, Patches, cutaneous, 21t actions, and dosage of, 585 Patient controlled analgesia (PCA), 323 Papanicolaou smear, 290–291 Patient preparation, for surgery, 341–342 Paper, for electrocardiography, 368 Pavulon (pancuronium), indications, Papillary muscle rupture, 393–394 actions, and dosage of, 585 Papules, 21t Paxil (paroxetine), indications, actions, Paracentesis, peritoneal (abdominal), and dosage of, 585 296–297, 298f Pediacare 1 (dextromethorphan), Paracoccidioidomycosis, systemic drug indications, actions, and dosage of, for treating, 152t 525 Paradoxical pulse, 393, 394f Pediazole (erythromycin + sulfisoxazole), Paraflex (hlorzoxazone), indications, indications, actions, and dosage of, actions, and dosage of, 515–516 534 Parafon Forte DSC (hlorzoxazone), Pediculus capitis, drugs for treating, indications, actions, and dosage of, 153t 515–516 Pediculus humanus infections, drugs for Paraldehyde, for seizures, 473t treating, 153t Paranasal sinus radiographs, 326 PEG tubes, 214 Paraplatin (carboplatin), indications, Pelvic drug therapy, 330 actions, and dosage of, 510 Pelvic examination, 289–291 Parasites indications for, 289 drugs for treating infections by, materials for, 289 153t–154t procedures for, 289–291 stool for, 131 Pelvic inflammatory disease (PID), transfusion-associated risk of organisms responsible and empiric transmission, 204 therapy for, 139t in urine sediment, 112 Pelvic magnetic resonance imaging, 333 Parathyroid hormone (PTH) Pelvic ultrasound, 330 deficiency of, hypocalcemia and, 189 Penbutolol (Levatol), indications, actions, hypocalcemia and, 189 and dosage of, 585 laboratory diagnosis and, 84 Penciclovir (Denavir), indications, actions, Paregoric, indications, actions, and dosage and dosage of, 147t, 585 of, 585 Penicillin(s), 477 Parenteral fluids, composition of, for dental abscesses, 470 178–179 Penicillin G, aqueous (potassium or Parenteral nutrition, 213–214, 434. See sodium) (Pentids; Pfizerpen), also Total parenteral nutrition indications, actions, and dosage of, (TPN) 586 Index 717 Penicillin G benzathine (Bicillin), Percutaneous nephrostography, 329 indications, actions, and dosage of, Percutaneous suprapubic bladder 586 aspiration, 309 Penicillin G procaine (Wycillin), Percutaneous transhepatic indications, actions, and dosage of, cholangiography (PTHC), 329 585 Performance status scales, 646, Penicillin V (Pen-Vee K; Veetids), 647t–648t indications, actions, and dosage of, Pergolide (Permax), indications, actions, 585 and dosage of, 587 Pentam 300 (pentamidine), indications, Periactin (cyproheptadine), indications, actions, and dosage of, 153t, 585 actions, and dosage of, 522 Pentamidine (Nebupent; Pentam 300), Pericardial friction rub, 394–395 indications, actions, and dosage of, Pericardiocentesis, 291–292, 293f 153t, 585 Pericarditis, on electrocardiograms, 387, Pentasa (mesalamine), indications, 387f actions, and dosage of, 566 Perindopril erbumine (Aceon), Pentazocine (Talwin), indications, actions, indications, actions, and dosage of, and dosage of, 586–587 587–588 Pentids [penicillin G, aqueous (potassium Peripherally inserted central catheter or sodium)], indications, actions, (PICC) lines, 292–295 and dosage of, 586 complications of, 295 Pentobarbital (Nembutal), indications, contraindications to, 293 actions, and dosage of, 587 historical background of, 294 Pentosan polysulfate sodium (Elmiron), indications for, 292 indications, actions, and dosage of, materials for, 293 587 procedure for, 294 Pentostatin (Nipent), indications, actions, removal of, 294–295 and dosage of, 587 Peritoneal dialysis, diet for, 208t Pentoxifylline (Trental), indications, Peritoneal lavage, 295–296, 296t actions, and dosage of, 587 Peritoneal paracentesis, 296–297, Pen-Vee K (penicillin V), indications, 298f actions, and dosage of, 585 complications of, 297 Pepcid (famotidine), indications, actions, contraindications to, 296–297 and dosage of, 537 diagnosis of ascitic fluid and, 297, Peptic ulcer disease, organism responsible 299t and empiric therapy for, 144t indications for, 296 Pepto-Bismol (bismuth subsalicylate), materials for, 297 indications, actions, and dosage of, procedure for, 297, 298f 505 Peritonitis, organisms responsible and Peptostreptococcus, Gram stain empiric therapy for, 139t characteristics of, 125t Permax (pergolide), indications, actions, Percocet (oxycodone + acetaminophen), and dosage of, 587 indications, actions, and dosage of, Permethrin (Elimite; Nix), indications, 583–584 actions, and dosage of, 153t, 154t, Percodan (oxycodone + aspirin), 588 indications, actions, and dosage of, Permitil (fluphenazine), indications, 584 actions, and dosage of, 541 Percodan-Demi (oxycodone + aspirin), Perphenazine (Trilafon), indications, indications, actions, and dosage of, actions, and dosage of, 588 584 Petechiae, 21t 718 Index Pfizerpen [penicillin G, aqueous example of, 28–32 (potassium or sodium)], written, 5 indications, actions, and dosage of, Physical therapy, for pain management, 586 320 pH Physostigmine (Antilirium) of pleural fluid, 299t for anticholinergic crisis, 470 of urine, 110–111 antidote for, 471 Phalen’s test, 26 indications, actions, and dosage Pharyngitis, organisms responsible and of, 589 empiric therapy for, 140t Phytonadione [vitamin K] Phenazopyridine (Pyridium), indications, (AquaMEPHYTON) actions, and dosage of, 588 indications, actions, and dosage of, 589 Phenelzine (Nardil), indications, actions, in total parenteral nutrition, 231 and dosage of, 588 Pindolol (Visken), indications, actions, Phenergan (promethazine), indications, and dosage of, 589 actions, and dosage of, 594 Pinworm infections, drugs for treating, Phenobarbital 153t half-life and therapeutic and toxic levels Pinworm preparation, 132 of, 631t Pioglitazone (Actos), indications, actions, indications, actions, and dosage of, 588 and dosage of, 589 for seizures, 473t Pipecuronium (Arduan), indications, Phenylephrine (Neo-Synephrine) actions, and dosage of, 590 indications, actions, and dosage of, Piperacillin (Pipracil), indications, actions, 398t, 588–589 and dosage of, 590 infusion guidelines for, 443t Piperacillin-tazobactam (Zosyn), Phenytoin (Dilantin) indications, actions, and dosage of, half-life and therapeutic and toxic levels 590 of, 631t–632t Pipracil (piperacillin), indications, actions, indications, actions, and dosage of, 589 and dosage of, 590 interaction with enteral nutrition, 223 Pirbuterol (Maxair), indications, actions, Phlebotomy, 309–314 and dosage of, 590 materials for, 309, 311t–312t Piroxicam (Feldene) procedure for, 310, 313–314 indications, actions, and dosage of, 590 Phos-Ex (calcium acetate), indications, route, effects, and dosage for, 321t actions, and dosage of, 508 Pitocin (oxytocin), indications, actions, PhosLo (calcium acetate), indications, and dosage of, 584 actions, and dosage of, 508 Pitressin (vasopressin) Phosphate indications, actions, and dosage of, 617 deficiency of, 192 infusion guidelines for, 443t excess of, 191–192 Plain catgut sutures, 346t Phospholine Ophthalmic (echothiophate Plaques, cutaneous, 21t iodine), indications, actions, and Plasmanate (plasma protein fraction), 200t dosage of, 532 Plasma protein fraction (Plasmanate), 200t Phosphorus, laboratory diagnosis and, 84 indications, actions, and dosage of, 590 Phrenilin Forte (acetaminophen + Plasmodium falciparum infections, drugs butalbital +/- caffeine), indications, for treating, 153t actions, and dosage of, 489 Plasmodium malariae infections, drugs Phthirus pubis infections, drugs for for treating, 153t treating, 153t Plasmodium ovale infections, drugs for Physical examination, 11–12 treating, 153t Index 719 Plasmodium vivax infections, drugs for Polycitra-K (potassium citrate + citric treating, 153t acid), indications, actions, and Platelet(s) dosage of, 592 laboratory diagnosis and, 103 Polydioxanone (PDS) sutures, 345, 346t for transfusion, 198t Polyester (Ethibond; Tycron) sutures, 347t transfusions of, 201 Polyethylene glycol [PEG]-electrolyte Plateletpheresis, 194 solution (CoLyte; GoLYTELY), Platinol AQ (cisplatin), indications, indications, actions, and dosage of, actions, and dosage of, 517 590–591 Plavix (clopidogrel), indications, actions, Polyglactin 910 (Vicryl) sutures, 346t and dosage of, 519 Polyglycolic acid 910 (Vicryl Rapide) Plendil (felodipine), indications, actions, sutures, 346t and dosage of, 537 Polyglyconate (Maxon) sutures, 346t Pleural effusion, differential diagnosis of, Polymerase chain reaction (PCR), 132 50 Polymorphonuclear neutrophils (PMNs) Pleural fluid, differential diagnosis of, bands or stabs, 100 299t, 306 laboratory diagnosis and, 103 Plicamycin (Mithracin) left shift and, 100 for hypercalcemia, 189 Polymox (amoxicillin) indications, actions, and dosage of, indications, actions, and dosage 590–591 of, 496 Pneumococcal vaccine, polyvalent for subacute bacterial endocarditis (Pneumovax-23), indications, prophylaxis, 158t, 159t actions, and dosage of, Polymyxin B + hydrocortisone (Otobiotic 590–591 Otic), indications, actions, and Pneumococcal 7-valent conjugate vaccine dosage of, 590–591 (Prevnar), indications, actions, and Poly-Pred Ophthalmic (neomycin, dosage of, 590–591 polymyxin-B, + prednisolone), Pneumocystis carinii pneumonia indications, actions, and dosage of, diagnosis of, 130 577 drugs for treating, 153t Polypropylene (Prolene) sutures, 347t Pneumonia, organisms responsible and Polysporin (bacitracin + polymyxin B, empiric therapy for, 135t, topical), indications, actions, and 140t–141t dosage of, 502 Pneumovax-23 (pneumococcal vaccine, Polysporin Ophthalmic (bacitracin + polyvalent), indications, actions, polymyxin B, ophthalmic), and dosage of, 590–591 indications, actions, and dosage of, Podocon-25 (podophyllin), indications, 502 actions, and dosage of, 148t, Portable chest x-rays, 325 590–591 Portagen, 224t Podofilox, indications and dosage for, Positive end-expiratory pressure (PEEP), 148t 417, 417f, 426 Podophyllin (Condylox; Condylox Gel Posteroanterior (PA) chest films, reading, 0.5%; Podocon-25), indications, 335, 336f, 338 actions, and dosage of, 148t, Postop notes, 36–37 590–591 Postrenal renal failure, 433 Poisoning, 471–472 Potassium Poliglecaprone 25 (Monocryl) sutures, deficiency of. See Hypokalemia 346t excess of. See Hyperkalemia Polychromasia, 104 requirement for, 178 720 Index Potassium (continued ) Prazosin (Minipress), indications, actions, serum, laboratory diagnosis and, 84 and dosage of, 593 spot urine study for, 114 Precordial contusion, 392 Potassium acetate, potassium citrate, + Precordial electrodes, 267, 267f bicarbonate (Tri-K), form and Precose (acarbose), indications, actions, dosage of, 626t and dosage of, 488 Potassium bicarbonate, for renal tubular Pred-G Ophthalmic (gentamicin + acidosis, 168t prednisolone, ophthalmic), Potassium chloride (Kaochlor 10%; indications, actions, and dosage of, Kaochlor S-F 10%; Kaon-Cl; 545 Kaon-Cl 20%; K-Lor; Klorvess; Predictive value, definition of, 645 Klotrix; K-Tab; Micro-K; Slow- Prednicarbate (Dermatop), potency and K), form and dosage of, 626t application of, 630t indications, actions, and dosage of, 592 Prednisolone (Delta-Cortef) Potassium chloride, potassium citrate, and dose, activity, duration, and route for, bicarbonate (Kaochlor Eff), form 627t and dosage of, 626t indications, actions, and dosage of, 603 Potassium citrate (Urocit-K), indications, Prednisone (Deltasone) actions, and dosage of, 590–591 dose, activity, duration, and route for, Potassium citrate + citric acid (Polycitra- 627t K), indications, actions, and for hypercalcemia, 189 dosage of, 592 indications, actions, and dosage of, 603 Potassium citrate + potassium gluconate Preemie SMA 20, 225t (Twin-K), form and dosage of, Preemie SMA 24, 225t 626t Pregnancy precautions, 156 Potassium gluconate (Glu-K; Kaon; Kaon Preload, 395, 396f elixir) measurement of, 408, 410 form and dosage of, 626t Premarin (estrogens, conjugated), indications, actions, and dosage of, 592 indications, actions, and dosage of, Potassium hydroxide preparation, 291 535 Potassium phosphate (K-Phos), for Premarin + Methylprogesterone hypophosphatemia, 192 (estrogens, conjugated + Pound/kilogram conversion, 658, 658t methylprogesterone), indications, Povidone-iodine hand scrub, 340–341 actions, and dosage of, 535–536 PPD test, 303–304 Premarin + Methyltestosterone

(estrogens, Pramipexole (Mirapex), indications, conjugated + methyltestosterone), actions, and dosage of, 592 indications, actions, and dosage of, Pramoxine (Anusol Ointment; 536 Proctofoam-NS), indications, Premature atrial contractions (PACs), 372, actions, and dosage of, 592 373f Pramoxine + hydrocortisone (Enzone; Premature infant(s), feeding, 225–226 Proctofoam-HC), indications, formulas for, 225t actions, and dosage of, 592 Premature ventricular contractions Prandin (repaglinide), indications, actions, (PVCs), 375–376, 376f, 377f and dosage of, 598 Preoperative notes, 36 Pravastatin (Pravachol), indications, Prerenal renal failure, 433 actions, and dosage of, 592–593 Prescriptions Prazepam (Centrax), indications, actions, safe, tips for, 39 and dosage of, 593 writing, 37–39, 38f Praziquantel, indications for, 154t Presentation, 5 Index 721 Present illness, history of, 9 Procarbazine (Matulane), indications, Pressor agents, 480 actions, and dosage of, 593–594 Pressure-limited ventilators, 423 Procardia (nifedipine), indications, Pressure regulated volume control actions, and dosage of, 578 ventilation, 426 Procardia XL (nifedipine), indications, Pressure support ventilation (PSV), 425f, actions, and dosage of, 578 426 Prochlorperazine (Compazine), Prevacid (lansoprazole), indications, indications, actions, and dosage of, actions, and dosage of, 558 594 Prevalence, definition of, 639 Procrit (epoetin alfa), indications, actions, Prevnar (pneumococcal 7-valent conjugate and dosage of, 533 vaccine), indications, actions, and Proctitis, organism responsible and dosage of, 590–591 empiric therapy for, 135t Priftin (rifapentine), indications, actions, Proctofoam-HC (pramoxine + and dosage of, 598 hydrocortisone), indications, Prilosec (omeprazole), indications, actions, and dosage of, 592 actions, and dosage of, 580–581 Proctofoam-NS (pramoxine), indications, Primacor (milrinone), indications, actions, actions, and dosage of, 592 and dosage of, 571 Proctoscopy, 300 Primaxin (imipenem-cilastin), indications, Procyclidine (Kemadrin), indications, actions, and dosage of, 552 actions, and dosage of, 594 Primidone, half-life and therapeutic and Progesterone, laboratory diagnosis and, 84 toxic levels of, 632t Progesterone receptors, laboratory Prinivil (lisinopril) diagnosis and, 67 for emergency cardiac care, 461 Progestimil, 224t indications, actions, and dosage Proglycem (diazoxide), indications, of, 562 actions, and dosage of, 526 PR interval, 367, 369f Prograf (tacrolimus), indications, actions, Priscoline (tolazoline), indications, and dosage of, 606 actions, and dosage of, 612 Progress notes Pro-Banthine (propantheline), indications, ICU, 389–391 actions, and dosage of, 594 problem-oriented, 34 Probenecid (Benemid), indications, Prohibit (haemophilus B conjugate actions, and dosage of, 593 vaccine), indications, actions, and Problem-oriented progress notes, 34 dosage of, 547 Procainamide (Procan; Pronestyl) Prokine (sargramostim), indications, electrocardiogram and, 386 actions, and dosage of, 600 for emergency cardiac care, 466 Prolactin, laboratory diagnosis and, 85 half-life and therapeutic and toxic levels Prolastin (α1-Protease inhibitor), of, 633t indications, actions, and dosage of, indications, actions, and dosage of, 593 492 infusion guidelines for, 443t Prolene (polypropylene) sutures, 347t Procaine (Novocain), for suturing, 349t Proleukin (aldesleukin), indications, Procan (procainamide) actions, and dosage of, 491 electrocardiogram and, 386 Prolixin (fluphenazine), indications, for emergency cardiac care, 466 actions, and dosage of, 541 half-life and therapeutic and toxic levels Proloprim (trimethoprim), indications, of, 633t actions, and dosage of, 615 indications, actions, and dosage of, 593 Promethazine (Phenergan), indications, infusion guidelines for, 443t actions, and dosage of, 594 722 Index Pronestyl (procainamide) Prostatic acid phosphatase (PAP), electrocardiogram and, 386 laboratory diagnosis and, 55 for emergency cardiac care, 466 Prostatitis, organisms responsible and half-life and therapeutic and toxic levels empiric therapy for, 144t of, 633t Prostep (nicotine, transdermal), indications, actions, and dosage indications, actions, and dosage of, of, 593 578 infusion guidelines for, 443t Prosthetic joint infections, organisms Propafenone (Rhythmol), indications, responsible and empiric therapy actions, and dosage of, 594 for, 134t Propantheline (Pro-Banthine), indications, Prosthetic valves, anticoagulant standard actions, and dosage of, 594 of practice for, 637t Propecia (finasteride), indications, actions, Prostin VR (alprostadil), indications, and dosage of, 539 actions, and dosage of, 492 Propine (dipivefrin), indications, actions, Protamine sulfate, indications, actions, and dosage of, 528 and dosage of, 595 Propionibacterium acne, Gram stain α1-Protease inhibitor (Prolastin), characteristics of, 126t indications, actions, and dosage of, Propofol (Diprivan), indications, actions, 492 and dosage of, 594 Protein Propoxyphene (Darvon), indications, needs for, 213 actions, and dosage of, 595 serum, laboratory diagnosis and, 87–88 Propoxyphene + acetaminophen spot urine study for, 115 (Darvocet), indications, actions, in urine, 112, 117–118 and dosage of, 595 Protein electrophoresis Propoxyphene + aspirin (Darvon serum, laboratory diagnosis and, 85, Compound-65; Darvon-N + 86f, 87t Aspirin), indications, actions, and urine, laboratory diagnosis and, dosage of, 595 85, 86f Propranolol (Inderal) Protein hydrosylate infant formulas, 224t for emergency cardiac care, 462 Proteus, Gram stain characteristics of, indications, actions, and dosage 124f of, 595 Proteus mirabilis, Gram stain Propylthiouracil [PTU], indications, characteristics of, 126t actions, and dosage of, 595 Proteus vulgaris, Gram stain Proscar (finasteride), indications, actions, characteristics of, 126t and dosage of, 539 Prothrombin complex, 200t ProSobee, 224t Prothrombin time (PT), 107–108 Prosom (estazolam), indications, actions, Protonix (pantoprazole), indications, and dosage of, 534 actions, and dosage of, 585 Prostaglandin E1 [alprostadil] (Prostin Proventil (albuterol), 364 VR), indications, actions, and for anaphylaxis, 469 dosage of, 492 indications, actions, and dosage of, 490 Prostaphlin (oxacillin), indications, nebulized, for asthmatic attacks, 469 actions, and dosage of, 582–583 Provera (medroxyprogesterone), Prostate cancer indications, actions, and dosage of, screening recommendations for, 643t 564 staging of, 657–658 Providencia, Gram stain characteristics of, Prostate-specific antigen (PSA), 127t laboratory diagnosis and, 85 Proximal port, of Swan-Ganz catheter, 399 Index 723 Prozac (fluoxetine), indications, actions, algorithm for, 460f and dosage of, 541 Pulmonary function tests (PFTs), Pruritus, differential diagnosis of, 50 359–361, 360f Pseudoephedrine (Afrinol; Novafed; differential diagnosis of, 361, 361t Sudafed), indications, actions, and Pulmonary vascular resistance (PVR), dosage of, 595–596 derivation and normal values for, Pseudo-hyponatremia, 185 437t Pseudomonas, Gram stain characteristics Pulmonic insufficiency (PI), 16t of, 124f Pulmonic stenosis (PS), 16t Pseudomonas aeruginosa, Gram stain Pulmozyme (dornase alfa), indications, characteristics of, 127t actions, and dosage of, 530 Pseudotumor cerebri, cerebrospinal fluid Pulseless electrical activity algorithm, in, 288t 453f Psoas sign, 26 Pulseless ventricular tachycardia Psorcon (diflorasone diacetate), potency algorithm, 452f and application of, 628t Pulse oximetry, for cardiac output Psychiatric history and physical, 13–14 determination, 413 Psychiatric mental status examination, 13 Pulse pressure, 393 Psychologic examination, for pain Pulsus alternans, 26 evaluation, 319 Pulsus paradoxus measurement, 298–300 Psychologic intervention, for pain Pureed diet, 206t management, 320 Purinethol (mercaptopurine), indications, Psychosocial history, 10 actions, and dosage of, 566 Psyllium (Effer-Syllium; Metamucil; Purpura, 21t Serutan), indications, actions, and Pustules, 21t dosage of, 596 P wave, 368 Pulmicort (budesonide), indications, Pyelonephritis, organisms responsible and actions, and dosage of, 506 empiric therapy for, 144t Pulmonary angiography, 328 Pyrantel pamoate, indications for, 153t, Pulmonary artery catheters, 399–410, 400f 154t catheterization procedure with, Pyrazinamide, indications, actions, and 402–404, 403f–405f, 406, 407t dosage of, 596 catheters for, 399–402, 401f, 402f Pyridium (phenazopyridine), indications, clinical applications of, 408, 410 actions, and dosage of, 588 complications of, 406–407 Pyridoxine [vitamin B6] differential diagnosis using, 408, 409t indications, actions, and dosage of, 596 indications for, 399 in total parenteral nutrition, 231t measurements using, 407–408 Pyrimethamine, indications for, 154t Pulmonary artery occlusion pressure, 407 Pyrimethamine-sulfadoxine, indications Pulmonary artery pressure, 407 for, 153t Pulmonary artery pressure, Pyrosis, differential diagnosis of, 47 systolic/diastolic (PAS/PAD), derivation and normal values for, 437t Q Pulmonary capillary wedge pressure QRS axis, 370 (PCWP), derivation and normal QRS complex, 369 values for, 437t QRS interval, 367, 369f Pulmonary disease, total parenteral QT interval, 367, 369f nutrition formulation for, 235 Quazepam (Doral), indications, actions, Pulmonary embolism, 435–436 and dosage of, 596 724 Index Queckenstedt’s test, 26 Rapamycin [sirolimus] (Rapamune), Quelicin (succinylcholine), indications, indications, actions, and dosage of, actions, and dosage of, 605 602 Questran (cholestyramine), indications, Rapid plasma reagin (RPR), laboratory actions, and dosage of, 516 diagnosis and, 92 Quetiapine (Seroquel), indications, Raynaud’s phenomenon/disease, 27 actions, and dosage of, 596 Reading, 4–5 Quinaglute (quinidine) Rebetron (ribavirin), indications, actions, electrocardiogram and, 386 and dosage of, 146t, 148t, 598 half-life and therapeutic and toxic levels Recombivax-HB (hepatitis B vaccine), of, 633t indications, actions, and dosage of, indications, actions, and dosage of, 548 596–597 Rectovaginal examination, 290 Quinapril (Accupril), indications, actions, Red blood cell(s) (RBCs) and dosage of, 596 abnormalities of, differential diagnosis Quinidine (Quinaglute; Quinidex) of, 104 electrocardiogram and, 386 laboratory diagnosis and, 68 half-life and therapeutic and toxic levels mass of, 177 of, 633t morphologic abnormalities of, spot indications, actions, and dosage of, urine study for, 114–115 596–597 nucleated, 104 Quinine dihydrochloride, indications for, transfusions of, 196, 197t, 201 153t in urine sediment, 112 Quinine gluconate, indications for, 153t washed, 197t Quinine sulfate, indications for, 153t Red blood cell (RBC) casts, in urine Quinke’s sign, 27 sediment, 114 Quinupristin + dalfopristin (Synercid), Red cell distribution width (RDW), indications, actions, and dosage of, laboratory diagnosis and, 103 597 Red rubber catheter, 307 Q waves, 369 Reducing substances, in urine, 112 in myocardial infarction, 384, 385f Refludan (lepirudin), indications, actions, and dosage of, 559 Reglan (metoclopramide), indications, R actions, and dosage of, 569 Rabeprazole (Aciphex), indications, Regranex Gel (becaplermin), indications, actions, and dosage of, 597 actions, and dosage of, 503 Racemic epinephrine, 364 Regular diet, 206t Radiation, for pain management, 320 Regular Iletin II, onset, peak, and duration Radiation terminology, 646 of effect of, 622t Radovici’s sign, 27 Relafen (nabumetone), indications, RA latex test, laboratory diagnosis and, 88 actions, and dosage of, 574 Raloxifene (Evista), indications, actions, Relenza (zanamivir), indications, actions, and dosage of, 597 and dosage of, 147t, 619 Ramipril (Altace) Remeron (mirtazapine), indications, for emergency cardiac care, 461 actions, and dosage of, 572 indications, actions, and dosage of, 597 Remicade (infliximab), indications, Random urine studies, 114–115 actions, and dosage of, 553 Ranitidine (Zantac) Renal cancer, staging of, 652–653 for anaphylaxis, 469 Renal failure indications, actions, and dosage of, 597 acute, 207t, 432–433 Index 725 diet for, 207t Retinoic acid [tretinoin, topical] (Avita; hypercalcemia with, 188 Retin-A), indications, actions, and renal, 433 dosage of, 613 total parenteral nutrition formulation Retinol-binding protein (RBP), laboratory for, 235–236 diagnosis and, 88 Renal scans, 334 Retrograde pyelography (RPG), 329 Renal tubular acidosis, diagnosis and Retrograde urethrography (RUG), 329 management of, 168t Retroperitoneal computed tomography, Renin, laboratory diagnosis and, 88 330 ReoPro (abciximab) Revia (naltrexone), indications, actions, for emergency cardiac care, 464 and dosage of, 575 indications, actions, and dosage of, 488 Review of systems (ROS), 10–11 Repaglinide (Prandin), indications, Rheomacrodex (dextran 40), indications, actions, and dosage of, 598 actions, and dosage of, 525 Repan (acetaminophen + butalbital +/- Rheumatoid factor, laboratory diagnosis caffeine), indications, actions, and and, 88 dosage of, 489 Rheumatrex (methotrexate) Rescriptor (delavirdine), indications, half-life and therapeutic and toxic levels actions, and dosage of, 523–524 of, 633t Residents, 1–2 indications, actions, and dosage Residual volume (RV), 361, 361t, 416 of, 568 Resin uptake, laboratory diagnosis and, 90 Rhinocort (budesonide), indications, Respiratory acidosis, 164t, 169–170 actions, and dosage of, 506 differential diagnosis of, 169–170 Rho Gam, 199t treatment of, 170 Rhythmol (propafenone), indications, Respiratory agents, 487 actions, and dosage of, 594 Respiratory alkalosis, 164t, 170–171 Rib(s), x-rays of, 325 differential diagnosis of, 170 Ribavirin (Rebetron; Virazole), treatment of, 170–171 indications, actions, and dosage of, Respiratory inhalants, 487 146t, 148t, 598 Respiratory isolation, 155 Riboflavin, in total parenteral nutrition, Respiratory procedures, subacute bacterial 231t endocarditis prophylaxis for, 158t Rickettsia rickettsii infections, Respiratory syncytial virus (RSV), drug of characteristics and treatment of, choice for treating infections by, 156t–157t 148t Rifabutin (Mycobutin), indications, Respiratory therapy, 359 actions, and dosage of, 598 Responsibility, 5–6 Rifampin (Rifadin), indications, actions, Restoril (temazepam), indications, actions, and dosage of, 598 and dosage of, 607 Rifapentine (Priftin), indications, actions, Reteplase (Retavase), indications, actions, and dosage of, 598 and dosage of, 598 Right atrial enlargement (RAE), Reticulocyte count, 100–101 electrocardiogram and, 380, 381f Retin-A (tretinoin, topical), indications, Right atrial pressure (RAP), derivation actions, and dosage of, 613 and normal values for, 437t Retinitis, cytomegalovirus, drugs of Right bundle branch block (RBBB), 379, choice for treating, 146t 380f Retinoic acid [tretinoin, systemic] Right shift, 100 (Vesanoid), indications, actions, Right ventricular ejection catheters, 401 and dosage of, 613 Right ventricular ejection fraction, 408 726 Index Right ventricular end-diastolic volume Rofecoxib (Vioxx) index, 408 indications, actions, and dosage of, 599 Right ventricular hypertrophy (RVH), route, effects, and dosage for, 321t electrocardiogram and, 381, 382f Roferon-A (interferon alfa-2a), indications Right ventricular pressure (RVP), and dosage for, 146t, 554 derivation and normal values for, Rogaine (minoxidil), indications, actions, 437t and dosage of, 572 Rimantadine (Flumadine), indications, Romazicon (flumazenil) actions, and dosage of, 148t, for benzodiazepine poisoning, 471 598–599 for emergency cardiac care, 462 Rimexolone (Vexol Ophthalmic), indications, actions, and dosage of, 540 indications, actions, and dosage of, Romberg’s test, 27 597–598 Rosiglitazone (Avandia), indications, Rimso 50 (dimethyl sulfoxide), actions, and dosage of, 599–600 indications, actions, and dosage of, Roth’s

spots, 27 528 Rounds, 3–4 Ringworm, organisms responsible and Roundworm infections, drugs for treating, empiric therapy for, 142t 153t Riopan (magaldrate), indications, actions, Rovsing’s sign, 27 and dosage of, 564 Rowasa (mesalamine), indications, Risedronate (Actonel), indications, actions, and dosage of, 566 actions, and dosage of, 599 Roxanol (morphine) Risperidone (Risperdal), indications, for emergency cardiac care, 465 actions, and dosage of, 599 indications, actions, and dosage of, 573 Ritonavir (Norvir), indications, actions, route, effects, and dosage for, 321t and dosage of, 150t, 599 Roxicodone (oxycodone), indications, Rivastigmine (Exelon), indications, actions, and dosage of, 583 actions, and dosage of, 599 Rubex (doxorubicin), indications, actions, Rizatriptan (Maxalt), indications, actions, and dosage of, 531 and dosage of, 599 Rufen (Ibuprofen) Robaxin (methocarbamol), indications, indications, actions, and dosage of, 551 actions, and dosage of, 568 route, effects, and dosage for, 321t Robetron (interferon alfa-2B + ribavirin “Rule of nines,” for calculating extent of combination ), indications, actions, burns, 182f, 183 and dosage of, 554 “Rule of sixes,” for calculating fluids in Robinson catheter, 307 children, 179, 181t Robitussin (guaifenesin), indications, “Rule of thumb” method, for calculating actions, and dosage of, 546 caloric needs, 213 Robitussin A-C (guaifenesin + codeine), R wave, 369 indications, actions, and dosage of, 546 Rocaltrol (calcitriol), indications, actions, S and dosage of, 508 Salem-sump tubes, 272 Rocephin (ceftriaxone), indications, Salmeterol (Serevent), indications, actions, and dosage of, 513 actions, and dosage of, 600 Rocky Mountain spotted fever (RMSF) Salmonella, Gram stain characteristics of, antibodies to, laboratory diagnosis and, 124f, 127t 88 Sandimmune (cyclosporine) characteristics and treatment of, half-life and therapeutic and toxic levels 156t–157t of, 634t Index 727 indications, actions, and dosage of, Seldinger technique, for femoral artery 521–522 cannulation, 245 Sandoglobulin (immune globulin, Selegiline (Eldepryl), indications, actions, intravenous), indications, actions, and dosage of, 600 and dosage of, 552 Selenium, in total parenteral nutrition, Sandostatin (octreotide), indications, 232t actions, and dosage of, 580–581 Selenium sulfide (Exsel Shampoo; Selsun Saquinavir (Fortovase), indications, Blue Shampoo; Selsun Shampoo), actions, and dosage of, 150t, 600 indications, actions, and dosage of, Sarafem (fluoxetine), indications, actions, 600 and dosage of, 541 Selsun Blue Shampoo (selenium sulfide), Sarcoptes scabiei infections, drugs for indications, actions, and dosage of, treating, 154t 600 Sargramostim [GM-CSF] (Leukine; Selsun Shampoo (selenium sulfide), Prokine), indications, actions, and indications, actions, and dosage of, dosage of, 600 600 Scabies, drugs for treating, 154t Semen analysis, laboratory diagnosis and, Scales, cutaneous, 21t 88–89 Scalpels, 240, 242f Sengstaken-Blakemore tubes, 273 Scalp vein needles, 280 Sensitivity, definition of, 645 Scars, 21t Sensoricaine (bupivacaine) Schedules of controlled substances, indications, actions, and dosage of, 507 475–476 for suturing, 349t Schistocytes, 104 Sentinel loop, 27 Schlichter test, 133 Sepsis Schmorl’s nodes, 27 total parenteral nutrition for, 236 Scoliosis, 27 total parenteral nutrition formulation Scopolamine, indications, actions, and for, 236 dosage of, 600 transfusions and, 202, 203 Scopolamine, transdermal (Transderm Septic arthritis Scop), indications, actions, and organisms responsible and empiric dosage of, 600 therapy for, 134t Scotch tape test, 132 synovial fluid interpretation and, 250, Scout films, 326 251t Screen film mammography, 326 Septic shock, 414, 431 Secobarbital (Seconal), indications, Septra (trimethoprim-sulfamethoxazole), actions, and dosage of, 600 indications, actions, and dosage of, Second-degree heart block, 377–378, 379f 153t, 615 Secretion precautions, 156 Serax (oxazepam), indications, actions, Sectral (acebutolol), indications, actions, and dosage of, 583 and dosage of, 488 Serentil (mesoridazine), indications, Sedapap-10 Two-dyne (acetaminophen + actions, and dosage of, 567 butalbital +/− caffeine), Serevent (salmeterol), indications, actions, indications, actions, and dosage of, and dosage of, 600 489 Seroquel (quetiapine), indications, actions, Sedative hypnotics, 481 and dosage of, 596 Sedimentation rate, 108 Serratia, Gram stain characteristics of, Segs, 100 124f, 127t Seizures, 472, 473t Serratia marcescens, Gram stain differential diagnosis of, 50 characteristics of, 127t 728 Index Sertraline (Zoloft), indications, actions, Simvastatin (Zocor), indications, actions, and dosage of, 601 and dosage of, 601 Serum(s), 485 Sinemet (carbidopa + levodopa), Serum bactericidal level, 133 indications, actions, and dosage of, Serutan (psyllium), indications, actions, 509–510 and dosage of, 596 Sinequan (doxepin) Serzone (nefazodone), indications, half-life and therapeutic and toxic levels actions, and dosage of, 576 of, 634t Shigella, Gram stain characteristics of, indications, actions, and dosage of, 530 124f, 127t Single donor plasma, 199t Shock, 413–414, 431 Single-photon emission computed algorithm for, 460f tomography (SPECT), 335 Shock lung, 429–431 Singulair (montelukast), indications, Shunt fraction (Qs/Qt), 419–423, actions, and dosage of, 573 420f–422f Singultus, differential diagnosis of, 48 derivation and normal values Sinography, 328 for, 438t Sinus arrhythmia, 372 Sibutramine (Meridia), indications, Sinus bradycardia, 371–372, 375f actions, and dosage of, 601 Sinus films, 326 Sickling, 104 Sinusitis, organisms responsible and Sigmoidoscopy, 300–302 empiric therapy for, 141t complications of, 302 Sinusoidal pattern, 276 indications for, 300 Sinus rhythms, on electrocardiograms, materials for, 300 371–372, 372f–373f procedure for, 200–201, 201f Sinus tachycardia, 371, 375f Signal sentinel sign, 27 SI prefixes and symbols, 646 Sildenafil (Viagra), indications, actions, Sirolimus [rapamycin] (Rapamune), and dosage of, 601 indications, actions, and dosage of, Silent heart algorithm, 454f 602 Silk sutures, 347t Sister Mary Joseph’s sign/node, 27 Silvadene (silver sulfadiazine), Skelaxin (metaxalone), indications, indications, actions, and dosage of, actions, and dosage of, 567 601 Skin Silver nitrate (Dey-Drop), indications, innervation of, 22f–23f actions, and dosage of, 601 melanoma of, staging of, 654–655 Silver sulfadiazine (Silvadene), Skin biopsy, 302 indications, actions, and dosage of, Skin infections, organisms responsible and 601 empiric therapy for, 141t–142t Simethicone (Mylicon), indications, Skin precautions, 155 actions, and dosage of, 601 Skin staples, 252, 258f Similac 13, 224t Skin testing, 303–304 Similac 20, 224t Skull films, 326 Similac 24, 224t Slow-K (potassium chloride) Similac 27, 224t form and dosage of, 626t Similac PM 60/40, 224t indications, actions, and dosage of, 592 Similac Special Care 20, 225t SMA 20, 224t Similac Special Care 24, 225t Small bowel follow-through (SBFT), 329 Simple acid-base disorders, 163 Small cells, 97, 100 Simulect (basiliximab), indications, SOAP, 34 actions, and dosage of, 502 Social history, 10 Index 729 Sodium indications, actions, and dosage of, deficiency of, 185–186, 237 603–604 excess of, 184–185 Solu-Medrol (methylprednisolone sodium requirement for, 178 succinate) serum, laboratory diagnosis and, 89 dose, activity, duration, and route for, spot urine study for, 114 627t total parenteral nutrition for deficiency indications, actions, and dosage of, 603 of, 237 Soma (carisoprodol), indications, actions, Sodium bicarbonate and dosage of, 510 for cyclic antidepressant poisoning, 471 Somatic pain, deep, 315 for emergency cardiac care, 466 Somophyllin (theophylline) for hyperkalemia, 187 half-life and therapeutic and toxic levels indications, actions, and dosage of, 602 of, 632t pediatric, for emergency cardiac care, indications, actions, and dosage 466 of, 609 for renal tubular acidosis, 168t Sonata (zaleplon), indications, actions, Sodium citrate (Bicitra), indications, and dosage of, 619 actions, and dosage of, 602 Sorbitol Sodium nitroprusside (Nipride; for hyperkalemia, 187 Nitropress) indications, actions, and dosage of, 602 for emergency cardiac care, 465–466 for poisoning, 472 for hypertensive crisis, 470 Sorbitrate (isosorbide dinitrate), indications, actions, and dosage of, 579 indications, actions, and dosage of, infusion guidelines for, 442t 555–556 Sodium phosphate (Fleet’s Phospho-soda), Soriatane (actretin), indications, actions, for hypophosphatemia, 192 and dosage of, 488 Sodium polystyrene sulfonate Sotalol (Betapace), indications, actions, (Kayexalate) and dosage of, 602 for hyperkalemia, 187 Soy infant formulas, 224t indications, actions, and dosage of, 602 Specific gravity, of urine, 111 Sodium-potassium phosphate (Neutra- Specificity, definition of, 645 Phos) Spectazole (econazole), indications, for hypercalcemia, 189 actions, and dosage of, 531–532 for hypophosphatemia, 192 Speculum examination Sodium salicylate (aspirin) bimanual examination, pelvic, 290 for emergency cardiac care, 461 pelvic, 290 indications, actions, and dosage of, Spermatozoa, in urine sediment, 112 499–500 Spherocytes, 104 route, effects, and dosage for, 321t Spinal headache, 286 Sodium Sulamyd (sulfacetamide), Spine computed tomography, 331 indications, actions, and dosage of, Spine magnetic resonance imaging, 333 605 Spiral computed tomography, 331 Soft diet, mechanical, 206t Spirometry, incentive, 363–364 Soft tissue infections, organisms Spironolactone (Aldactone), indications, responsible and empiric therapy actions, and dosage of, 603 for, 141t–142t Splenomegaly, differential diagnosis of, Solu-Cortef (hydrocortisone) 49 dose, activity, duration, and route for, Sporanox (itraconazole), indications, 627t actions, and dosage of, 151t, for hypercalcemia, 189 556–557 730 Index Sporotrichosis, systemic drug for treating, Stool leukocyte stain, 128 152t Straight-leg-raising sign, 26 Spot urine studies, 114–115 Strep screen, 131 Sputum, Gram stain of, 122 Streptase (streptokinase) Sputum culture, 130 for emergency cardiac care, 466 Square knots, 355f, 356f indications, actions, and dosage of, 604 Stab cells, 100 Streptococcus, Gram stain characteristics Stadol (butorphanol), indications, actions, of, 123f, 125t and dosage of, 507 Streptococcus agalactiae, Gram stain Staining techniques, 121–128 characteristics of, 123f Stainless steel sutures, 347t Streptococcus bovis, Gram stain Staphylococcus, Gram stain characteristics characteristics of, 125t of, 123f, 125t Streptococcus faecalis, Gram stain Staphylococcus agalactiae, Gram stain characteristics of, 125t characteristics of, 125t Streptococcus mutans, Gram stain Staphylococcus aureus, Gram stain characteristics of, 123f characteristics of, 123f, 125t Streptococcus pneumoniae, Gram stain Staphylococcus epidermidis, Gram stain characteristics of, 123f, 125t characteristics of, 123f, 125t Streptococcus pyogenes, Gram stain Staphylococcus saphrophyticus, Gram characteristics of, 123f, 125t stain characteristics of, 123f, 125t Streptococcus viridans, Gram stain Staples, skin, 252, 258f characteristics of, 125t Startle reflex, 26 Streptokinase (Kabikinase; Streptase) Staticin Topical (erythromycin, topical), for emergency cardiac care, 466 indications, actions, and dosage of, indications, actions, and dosage 534 of, 604 Status epilepticus, 472, 473t Streptomycin, indications, actions, and Stavudine (Zerit), indications, actions, and dosage of, 604 dosage of, 603 Streptozocin (Zanosar), indications, Stelazine (trifluoperazine), indications, actions, and dosage of, 604 actions, and dosage of, 614 Streptozyme, laboratory diagnosis and, 57 Stellwag’s sign, 27 Stress ulcers, 433 Stentrophomonas maltophilia, Gram stain Strict isolation, 155 characteristics of, 127t Stroke volume, measurement of, 408, 410 Sterile technique, 339 Strongyloidiasis, drugs for treating, 154t Steroids, systemic. See also specific Strontium-89, 334 steroids Subacute bacterial endocarditis (SBE), dose, activity, duration, and route for, prophylaxis of, 155, 158t–159t 627t Subarachnoid hemorrhage, 286 indications, actions, and dosage of, cerebrospinal fluid in, 288t 603–604 Subcutaneous injections, 276, 277 Steroids, topical. See also specific steroids Sublimaze (fentanyl) indications, actions, and dosage of, 604 indications, actions, and dosage of, 538 potency and application of, 628t–630t route, effects, and dosage for, 321t Stimate (desmopressin), indications, Succimer (Chemet), indications, actions, actions, and dosage of, 524 and dosage of, 604–605 Stomach cancer, staging of, 656 Succinylcholine (Anectine; Quelicin; Stool cultures, 130–131 Sucostrin), indications, actions, Stool for occult blood, laboratory and dosage of, 605 diagnosis and, 89 Sucostrin (succinylcholine), indications, Stool for ova and parasites, 131 actions, and dosage of, 605 Index 731 Sucralfate (Sufenta), indications, actions, Sustiva (efavirenz), indications, actions, and dosage of, 605 and dosage of, 532 Sudafed (pseudoephedrine), indications, Suturing, 345–358 actions, and dosage of, 595–596 materials for, 345, 346t–347t Sudan stain, of pleural fluid, 299t patterns for, 348, 350, 351f–354f Sufenta (sucralfate), indications, actions, procedure for, 345, 348, 349t, 350t and dosage of, 605 surgical knots for, 350, 355f–357f Sular (nisoldipine), indications, actions, suture removal and, 350, 353, 358f and dosage of, 579 Swan-Ganz catheters, 399–402, 401f, 402f Sulfacetamide (Bleph-10; Cetamide; S wave, 369 Sodium Sulamyd), indications, Sweat chloride, laboratory diagnosis and, actions, and dosage of, 605 89–90 Sulfacetamide + prednisolone Symmetrel (amantadine), indications, (Blephamide), indications, actions, actions, and dosage of, 148t, 494 and dosage of, 605 Sympathetic nervous system, 395, 397, Sulfadiazine, indications for, 154t 397t, 398t Sulfasalazine (Azulfidine), indications, Sympathomimetic drugs, actions of, 398t actions, and dosage of, 605–606 Synalar (fluocinolone acetonide), potency Sulfinpyrazone (Anturane), indications, and application of, 628t, 629t actions, and dosage of, 606 Synalar-HP (fluocinolone acetonide), Sulindac (Clinoril), indications, actions, potency and application of, 628t, and dosage of, 606 629t Sumatriptan (Imitrex), indications, Synchronous intermittent mandatory actions, and dosage of, 606 ventilation (SIMV), 424, 425f Sumycin (tetracycline) Syncope, differential diagnosis of, 51 indications, actions, and dosage of, Synercid (quinupristin + dalfopristin), 153t, 609 indications, actions, and dosage of, interaction with enteral nutrition, 223 597 Superchar (activated charcoal) Synovial fluid, interpretation of, 249–250, clinical use of, 472 251t indications, actions, and dosage of, 514 Synthroid (levothyroxine), indications, Superficial pain, 315 actions, and dosage of, 560–561 Suprapubic bladder aspiration, Syntocinon (oxytocin), indications, percutaneous, 309, 310f actions, and dosage of, 584 Supraventricular tachycardia algorithms Syphilis, organism responsible and for narrow complex SVT, 457f empiric therapy for, 143t for stable SVT, 458f Systemic inflammatory response Suprax (cefixime), indications, actions, syndrome (SIRS), 414 and dosage of, 511 Systemic vascular resistance (SVR), Surfak (docusate calcium), indications, derivation and normal values for, actions, and dosage of, 529 437t Surgery, nutritional support following, 223 Systolic heart murmurs, 393–394 Surgical cricothyrotomy, 263–264 Systolic hypertension, 392 Surgical hand scrub, 340–341

Surmontil (trimipramine), indications, actions, and dosage of, 615 Survanta (beractant), indications, actions, T and dosage of, 504 Tabloid (6-thioguanine), indications, Susceptibility testing, microbiologic, 133 actions, and dosage of, 609 Sus-Phrine. See Epinephrine (Adrenalin; Tachycardia, 276, 371 Sus-Phrine) algorithm for, 456f 732 Index Tacrine (Cognex), indications, actions, Technetium-99m DTPA and dosage of, 606 (diethylenetriamine pentaacetic Tacrolimus [FK 506] (Prograf), acid), 334 indications, actions, and dosage of, Technetium-99m glucoheptonate, 334 606 Technetium-99m Taenia saginata infections, drugs for mercaptoacetylthiglycine (MAG3), treating, 154t 334 Taenia solium infections, drugs for Technetium-99m pyrophosphate cardiac treating, 154t scans, 333 Tagamet (cimetidine), indications, actions, Technetium-99m sulfur colloid scans, 333 and dosage of, 516 Technetium-99m ventriculography, Talwin (pentazocine), indications, actions, 333–334 and dosage of, 586–587 Teeth Tambocor (flecainide) emergencies involving, 470 half-life and therapeutic and toxic levels eruption of, 17, 19f of, 633t Tegopen (cloxacillin), indications, actions, indications, actions, and dosage and dosage of, 519 of, 539 Tegretol (carbamazepine) Tamiflu (oseltamivir), indications, actions, half-life and therapeutic and toxic levels and dosage of, 147t, 582 of, 631t Tamoxifen (Nolvadex), indications, indications, actions, and dosage of, 509 actions, and dosage of, 606–607 route, effects, and dosage for, 322t Tamsulosin (Flomax), indications, actions, Telangiectasia, 21t and dosage of, 607 Telmisartan (Micardis), indications, Tapazole (methimazole), indications, actions, and dosage of, 607 actions, and dosage of, 568 Temazepam (Restoril), indications, Tapeworms, drugs for treating, 154t actions, and dosage of, 607 Target cells, 104 Temovate (clobetasol propionate), potency Tavist (clemastine fumarate), indications, and application of, 628t actions, and dosage of, 518 Temperature conversion, 646, 649t Taxol (paclitaxel), indications, actions, Tenecteplase (Tnkase), indications, and dosage of, 584 actions, and dosage of, 607 Taxotere (docetaxel), indications, actions, Tenex (guanfacine), indications, actions, and dosage of, 529 and dosage of, 547 Tazarotene (Tazorac), indications, actions, Teniposide [VM-26] (Vumon), and dosage of, 607 indications, actions, and dosage of, Tazicef (ceftazidime), indications, actions, 607–608 and dosage of, 513 Tenoretic (atenolol + chlorthalidone), Tazidime (ceftazidime), indications, indications, actions, and dosage of, actions, and dosage of, 513 500 Tazorac (tazarotene), indications, actions, Tenormin (atenolol) and dosage of, 607 for emergency cardiac care, 462 Teamwork, 2 indications, actions, and dosage of, 500 Tears Naturale (artificial tears), Tensilon (edrophonium), indications, indications, actions, and dosage of, actions, and dosage of, 532 499 Tequin (gatifloxacin), indications, actions, Technetium-99-labeled red cell scans, 333 and dosage of, 544 Technetium-99m DMSA Terazol (terconazole), indications, actions, (dimercaptosuccinic acid), 334 and dosage of, 608 Index 733 Terazosin (Hytrin), indications, actions, 6-Thioguanine [6-TG] (Tabloid), and dosage of, 608 indications, actions, and dosage of, Terbinafine (Lamisil), indications, actions, 609 and dosage of, 608 Thioridazine (Mellaril), indications, Terbutaline (Brethine; Bricanyl), actions, and dosage of, 609–610 indications, actions, and dosage of, Thio-Tepa (triethylenetriphosphoramide), 608 indications, actions, and dosage of, Terconazole (Terazol), indications, 614 actions, and dosage of, 608 Thiothixene (Navane), indications, TESPA (triethylenetriphosphoramide), actions, and dosage of, 610 indications, actions, and dosage of, Third-degree heart block, 378–379 614 Third heart sound (S3), 17t Testosterone, laboratory diagnosis Thoracentesis, 304–306 and, 90 complications of, 306 Tetanus immune globulin, indications, contraindications to, 304 actions, and dosage of, 608 differential diagnosis of pleural fluid Tetanus prophylaxis, 350t and, 299t, 306 Tetanus toxoid, indications, actions, and indications for, 304 dosage of, 608–609 materials for, 304 Tetracycline (Achromycin V; Sumycin) procedure for, 305f, 305–306 indications, actions, and dosage of, Thoracic catheters, 261 153t, 477, 609 Thoracostomy, closed (tube). See Chest interaction with enteral nutrition, 223 tube placement Teveten (eprosartan), indications, actions, Thorazine (chlorpromazine), indications, and dosage of, 533 actions, and dosage of, 515 Thallium-201 cardiac scans, 333 Three-cell differential count, 97, 100 Thayer-Martin medium, 129, 291 Throat cultures, 131 Theophylline (Somophyllin; Theo-Dur; Thrombin time, 108 Theolair) Through-and-through technique, for half-life and therapeutic and toxic levels arterial line placement, 244 of, 632t Thyrocalcitonin, laboratory diagnosis and, indications, actions, and dosage 61 of, 609 Thyroglobulin, laboratory diagnosis and, Thera Cys (BCG [bacillus Calmette- 90 Guérin]), indications, actions, and Thyroid agents, 482 dosage of, 503 Thyroid cancer, staging of, 656–657 Therapeutic apheresis, 194 Thyroid scans, 335 Thermal dilution technique, for cardiac Thyroid-stimulating hormone (TSH), output determination, 410 laboratory diagnosis and, 90 Thermistor, of Swan-Ganz catheter, 400 Thyroid ultrasound, 330 Thermography, for pain evaluation, 319 Thyroxine, laboratory diagnosis and, 90–91 Thiabendazole, indications for, 153t Thyroxine-binding globulin (TBG), Thiamine [vitamin B1] laboratory diagnosis and, 91 indications, actions, and dosage Thyroxine-binding globulin ratio, of, 609 laboratory diagnosis and, 90 for seizures, 472 Thyroxine index, free (FTI), laboratory in total parenteral nutrition, 231t diagnosis and, 91 Thiethylperazine (Torecan), indications, Tiagabine (Gabitril), indications, actions, actions, and dosage of, 609 and dosage of, 610 734 Index Tiazac (diltiazem) indications, actions, and dosage of, 611 for emergency cardiac care, 462 Tissue adhesives, 358 indications, actions, and dosage of, 528 201Tl cardiac scans, 333 infusion guidelines for, 439t Tnkase (tenecteplase), indications, TIBC (iron-binding capacity, total), actions, and dosage of, 607 laboratory diagnosis and, 78 TNM classification system, 646, 649–658 Ticarcillin (Ticar), indications, actions, Tobradex (tobramycin + dexamethasone, and dosage of, 610 ophthalmic), indications, actions, Ticarcillin + potassium clavulanate and dosage of, 611 (Timentin), indications, actions, Tobramycin (Nebcin) and dosage of, 610 half-life and therapeutic and toxic levels TICE (BCG [bacillus Calmette-Guérin]), of, 631t indications, actions, and dosage of, indications, actions, and dosage 503 of, 611 Tick-borne diseases. See also specific Tobramycin + dexamethasone, ophthalmic diseases (Tobradex), indications, actions, characteristics and treatment of, and dosage of, 611 156t–157t Tobramycin, ophthalmic (AK Tob; Ticlodipine (Ticlid), indications, actions, Tobrex), indications, actions, and and dosage of, 610 dosage of, 611 Tidal volume (TV), 360, 361t, 415 Tobrex (tobramycin, ophthalmic), Tigan (trimethobenzamide), indications, indications, actions, and dosage of, actions, and dosage of, 615 611 Tilade (nedocromil), indications, actions, Tocainide (Tonocard), indications, actions, and dosage of, 576 and dosage of, 611 Timed hand scrubs, 340–341 α Tocopherol, in total parenteral nutrition, Time management, 6–7 231t Timentin (ticarcillin + potassium Tofranil (imipramine), indications, clavulanate), indications, actions, actions, and dosage of, 552 and dosage of, 610 Tolazamide (Tolinase), indications, Timolol (Blocadren), indications, actions, actions, and dosage of, 611 and dosage of, 610 Tolazoline (Priscoline), indications, Timolol, ophthalmic (Timoptic), actions, and dosage of, 612 indications, actions, and dosage of, Tolbutamide (Orinase), indications, 611 actions, and dosage of, 612 Tinactin (tolnaftate), indications, actions, Tolectin (tolmetin), indications, actions, and dosage of, 612 and dosage of, 612 Tinea capitis, organisms responsible and Tolinase (tolazamide), indications, actions, empiric therapy for, 142t and dosage of, 611 Tinea corporis, organisms responsible and Tolmetin (Tolectin), indications, actions, empiric therapy for, 142t and dosage of, 612 Tinea unguium, organisms responsible and Tolnaftate (Tinactin), indications, actions, empiric therapy for, 142t and dosage of, 612 Tinel’s sign, 27 Tolterodine (Detrol; Detrol LA), Tine test, 303 indications, actions, and dosage of, Tinidazole, indications for, 153t, 154t 612 Tioconazole (Vagistat), indications, Tonocard (tocainide), indications, actions, actions, and dosage of, 611 and dosage of, 611 Tirofiban (Aggrastat) Toothaches, 470 for emergency cardiac care, 464 Tooth emergencies, 470 Index 735 Topamax (topiramate), indications, Trace elements, for total parenteral actions, and dosage of, 612 nutrition, 231, 232t Topicort (desoximetasone), potency and Tracrium (atracurium), indications, application of, 628t actions, and dosage of, 501 Topiramate (Topamax), indications, Tramadol (Ultram), indications, actions, actions, and dosage of, 612 and dosage of, 613 Topotecan (Hycamtin), indications, Trandate (labetalol) actions, and dosage of, 612 for emergency cardiac care, 462 Toprol XL (metoprolol) for hypertensive crisis, 470 for emergency cardiac care, 462 indications, actions, and dosage of, 557 indications, actions, and dosage of, 569 infusion guidelines for, 441t Toradol (ketorolac), indications, actions, Trandolapril (Mavik), indications, actions, and dosage of, 557 and dosage of, 613 Torch battery, laboratory diagnosis and, 91 Transcutaneous electrical nerve Torecan (thiethylperazine), indications, stimulation (TENS), 323 actions, and dosage of, 609 Transcutaneous pacing, 468 Tornalate (bitolterol), indications, actions, Transderm-Nitro (nitroglycerin) and dosage of, 505 for emergency cardiac care, 465 Torsemide (Demadex), indications, indications, actions, and dosage of, 579 actions, and dosage of, 613 Transderm Scop (scopolamine, Total blood volume, 177 transdermal), indications, actions, Total body water, 177 and dosage of, 600 Total CO2, laboratory diagnosis and, 59, Transferrin, laboratory diagnosis and, 91 61–62 Transfusion reactions, 202–203 Total lung capacity (TLC), 360, 361t Transfusion therapy. See Blood Total parenteral nutrition (TPN), 227–237, component therapy 434 Transgrow medium, 129 additives for, 231t, 231–232, 232t Transrectal ultrasound, 330 assessing, 234 Transtracheal aspirate, 130 calculation of caloric requirements in Transudative ascites, 297 stressed patients and, 228 Tranxene (clorazepate), indications, complications of, 236–237 actions, and dosage of, 519 disease-specific formulations for, Trasylol (aprotinin), indications, actions, 235–236 and dosage of, 499 fat emulsions for, 232–233 Traube’s sign, 27 indications for, 227 Trauma, total parenteral nutrition nitrogen balance and, 229 formulation for, 236 nutritional components in, 228 Traumatic tap, 286 peripheral, 230–231 cerebrospinal fluid in, 288t solutions for, 229–230, 230t Trazodone (Desyrel) starting, 233–234 half-life and therapeutic and toxic levels stopping, 234 of, 634t Toxic granulation, of white blood cells, indications, actions, and dosage of, 613 104 Tremors, differential diagnosis of, 51 Toxocara canis infections, drugs for Trendelenburg’s test, 27 treating, 154t Trental (pentoxifylline), indications, Toxoids, 485 actions, and dosage of, 587 Toxoplasma gondii infections, drugs for Tretinoin, systemic [retinoic acid] treating, 154t (Vesanoid), indications, actions, Toxoplasmosis, drugs for treating, 154t and dosage of, 613 736 Index Tretinoin, topical [retinoic acid] (Avita; Trilafon (perphenazine), indications, Retin-A), indications, actions, and actions, and dosage of, 588 dosage of, 613 Trileptal (oxcarbazepine), indications, Triamcinolone acetonide (Aristocort; actions, and dosage of, 583 Kenalog), potency and application Tri-Levlen 21, 28, 625t of, 630t Trimethobenzamide (Tigan), indications, Triamcinolone + nystatin (Mycolog-II), actions, and dosage of, 615 indications, actions, and dosage of, Trimethoprim (Proloprim; Trimpex), 613 indications, actions, and dosage of, Triamterene (Dyrenium), indications, 615 actions, and dosage of, 613–614 Trimethoprim-sulfamethoxazole [co- Triapin Axocet (acetaminophen + trimoxazole] (Bactrim; Septra), butalbital +/- caffeine), indications, indications, actions, and dosage of, actions, and dosage of, 489 153t, 615 Triazolam (Halcion), indications, actions, Trimetrexate (Neutrexin), indications, and dosage of, 614 actions, and dosage of, 615 Trichinosis, drugs for treating, 154t Trimipramine (Surmontil), indications, Trichomonas infection actions, and dosage of, 615 drugs for treating, 154t Trimpex (trimethoprim), indications, organism responsible and empiric actions, and dosage of, 615 therapy for, 145t Tri-Norinyl 21, 28, 625t test for, 291 Triphasil-21, 625t vaginal, 145t, 291 Trivora-28, 625t Trichostrongylus colubriformis infections, Troponin, cardiac-specific, laboratory drugs for treating, 154t diagnosis and, 92 Trichuriasis, drugs for treating, 154t Trousseau’s sign, 27 Tricor (fenofibrate), indications, actions, T3 RU, laboratory diagnosis and, 90 and dosage of, 537 Trusopt (dorzolamide), indications, Tricuspid insufficiency (TI), 16t actions, and dosage of, 530 Tridil (nitroglycerin), infusion guidelines Trypanosoma cruzi infections, drugs for for, 442t treating, 154t Triethanolamine (Cerumenex), Trypanosomiasis, drugs for treating, 154t indications, actions, and dosage of, TSPA (triethylenetriphosphoramide), 614 indications, actions, and dosage of, Triethylenetriphosphoramide (TESPA; 614 Thio-Tepa; TSPA), indications, T4 total, laboratory diagnosis and, actions, and dosage of, 614 90–91 Trifluoperazine (Stelazine), indications, T-tube cholangiography, 329 actions, and dosage of, 614 Tube feeding, 213, 214–223 Trifluridine (Viroptic), indications, complications of, 218, 223 actions, and dosage of, 147t, contraindications to, 214t 614 enteral products for, 214, 215t–216t, Trigeminy, 375 217 Triglycerides initiating, 217–218, 218t–222t laboratory diagnosis and, 91–92 Tuberculin skin testing (TST), 303–304 in pleural fluid, 299t Tuberculosis, organism responsible and Trihexyphenidyl (Artane), indications, empiric therapy for, 143t actions, and dosage of, 614 Tube thoracostomy. See Chest tube Triiodothyronine (T3 RIA), laboratory placement diagnosis and, 92 Tubular casts, in urine sediment, 114 Index 737 Tucks Pads (witch hazel), indications, Unasyn (ampicillin-sulbactam), actions, and dosage of, 618 indications, actions, and dosage of, Tumors. See Malignancies; Neoplasms 497 Tums (calcium carbonate) Univasc (moexipril), indications, actions, for hypocalcemia, 190 and dosage of, 573 indications, actions, and dosage of, 508 Universal/international advanced cardiac Turner’s sign, 27 life support algorithm, 450f T wave, 369 Universal Pedi-Packs, 197t 24-hour urine studies, 116–118 Universal precautions, 239–240, 344 Twin-K (potassium citrate + potassium Upper gastrointestinal (UGI) series, 329 gluconate), form and dosage of, Urate, laboratory diagnosis and, 92 626t Urecholine (bethanechol), indications, Two-dimensional echocardiography, 330 actions, and dosage of, 504–505 Tycron (polyester) sutures, 347t Urethritis Tylenol (acetaminophen) organism responsible and empiric antidote for, 471 therapy for, 135t indications, actions, and dosage of, 488, organisms responsible and empiric 621t therapy for, 143t–144t route, effects, and dosage for, 321t Urex (methenamine), indications, actions, Tylenol No. 1, No. 2, No. 4 and dosage of, 568 (acetaminophen + codeine), Uric acid, laboratory diagnosis and, 92 indications, actions, and dosage of, Urinalysis 489 differential diagnosis for, 110–112 Tylox (oxycodone + acetaminophen), normal values for, 110 indications, actions, and dosage of, procedure for, 109–110 583–584 Urinary agents, 487 Tzanck smear, 128 Urinary

incontinence, differential diagnosis of, 48 Urinary tract infections, organisms responsible and empiric therapy U for, 143t–144t Ulcers Urine cutaneous, 21t bilirubin in, 111 gastrointestinal, organism responsible blood in, 111 and empiric therapy for, 144t clean catch specimens of, 308–309 stress, 433 color of, 110 Ultracef (cefadroxil) glucose in, 111 indications, actions, and dosage of, 511 in-and-out catheterized, 308 for subacute bacterial endocarditis ketones in, 111 prophylaxis, 158t leukocyte esterase in, 112 Ultralente, onset, peak, and duration of nitrite in, 111 effect of, 622t output of, 119 Ultram (tramadol), indications, actions, pH of, 110–111 and dosage of, 613 protein electrophoresis of, 119 Ultrase (pancreatin + pancrelipase), protein in, 112 indications, actions, and dosage of, reducing substances in, 112 585 specific gravity of, 111 Ultrasound, 329–330 urobilinogen in, 112 Ultravate (halobetasol), potency and Urine cultures, 131–132 application of, 629t Urine sediment, 112, 113f, 114 738 Index Urine studies, 109–119 Valium (diazepam) creatinine and creatinine clearance, indications, actions, and dosage of, 115–116 525–526 drug abuse screen, 118 for seizures, 472, 473t indices useful in diagnosing oliguria, Valproic acid (Depakene) 119t half-life and therapeutic and toxic levels spot (random), 114–115 of, 632t 24-hour, 116–118 indications, actions, and dosage of, 616 urinalysis, 109–112 Valrubicin (Valstar), indications, actions, urine sediment, 112, 113f, 114 and dosage of, 616 xylose tolerance test, 118–119 Valsartan (Diovan), indications, actions, Urispas (flavoxate), indications, actions, and dosage of, 616 and dosage of, 539 Valstar (valrubicin), indications, actions, Urobilinogen, in urine, 112 and dosage of, 616 Urocit-K (potassium citrate), indications, Valtrex (valacyclovir), indications, actions, actions, and dosage of, and dosage of, 147t, 148t, 616 590–591 Valvular heart disease, anticoagulant Urokinase (Abbokinase), indications, standard of practice for, 637t actions, and dosage of, 615 Vancenase Nasal Inhaler Uterine cancer, staging of, 657 (beclomethasone), indications, UUN levels, 228 actions, and dosage of, 503 Vancomycin (Vancocin; Vancoled) half-life and therapeutic and toxic levels V of, 631t Vaccines, 485 indications, actions, and dosage of, 616 Vacutainer system, 313 for subacute bacterial endocarditis tubes for, 311t–312t prophylaxis, 159t Vaginal bleeding, differential diagnosis of, Vanillylmandelic acid, in urine, 118 51 Vantin (cefpodoxime), indications, Vaginal candidiasis actions, and dosage of, 512 organisms responsible and empiric Vaqta (hepatitis A vaccine), indications, therapy for, 144t actions, and dosage of, 548 systemic drugs for treating, 151t Variable decelerations, in fetal heart rate, Vaginal discharge, differential diagnosis 276 of, 51 Varicella, drugs of choice for treating, Vaginal infections 148t organisms responsible and empiric Varicella immune globulin (VZIG), therapy for, 144t–145t indications and dosage for, 148t tests for, 291 Varicella virus vaccine (Varivax), Vaginal preparations, 485 indications, actions, and dosage of, Vaginal saline (wet) preparation, 291 616 Vaginosis, bacterial, organism responsible Varicella zoster virus (VZV) and empiric therapy for, 145t cultures for, 132 Vagistat (tioconazole), indications, drugs of choice for treating infections actions, and dosage of, 611 by, 148t–149t Valacyclovir (Valtrex), indications, Varivax (varicella virus vaccine), actions, and dosage of, 147t, 148t, indications, actions, and dosage of, 616 616 Valisone (betamethasone valerate), Vascar (bepridil), indications, actions, and potency and application of, 628t dosage of, 504 Index 739 Vascular catheters. See also Central Ventricular fibrillation, 377, 378f venous catheterization; algorithm for, 452f Peripherally inserted central Ventricular septal defect (VSD), 17t catheter (PICC) lines; Pulmonary Ventricular tachycardia, 376–377, 378f artery catheters algorithm for, 452f sepsis of, 435 Ventriculography, technetium-99m, Vasodilators, 480 333–334 Vasopressin [antidiuretic hormone] Vepesid (etoposide), indications, actions, (Pitressin) and dosage of, 537 indications, actions, and dosage of, 617 Verapamil (Calan; Isoptin) infusion guidelines for, 443t for emergency cardiac care, 467 Vasotec (enalapril) indications, actions, and dosage of, 617 for emergency cardiac care, 449 Versed (midazolam) indications, actions, and dosage of, 532 indications, actions, and dosage of, 571 Vasoxyl (methoxamine), indications, for seizures, 472 actions, and dosage of, 568–569 Vertebral radiography, 326 Vecuronium (Norcuron), indications, Vertigo, differential diagnosis of, 51 actions, and dosage of, 617 Vesanoid (tretinoin, systemic), indications, Veetids (penicillin V), indications, actions, actions, and dosage of, 613 and dosage of, 585 Vesicles, 21t Veillonella, Gram stain characteristics of, Vexol Ophthalmic (rimexolone), 125t indications, actions, and dosage of, Velban (vinblastine), indications, actions, 597–598 and dosage of, 617 Viadar, 559 Velbe (vinblastine), indications, actions, Viagra (sildenafil), indications, actions, and dosage of, 617 and dosage of, 601 Velosef (cephradine), indications, actions, Vibramycin (doxycycline), indications, and dosage of, 514 actions, and dosage of, 153t, 531 Velosulin, onset, peak, and duration of Vibrio cholerae, Gram stain characteristics effect of, 622t of, 127t Venereal Disease Research Laboratory Vicodin (hydrocodone + acetaminophen), (VDRL) test, 92 indications, actions, and dosage of, Venipuncture, 309–314 549 materials for, 309, 311t–312t Vicoprofen (hydrocodone + ibuprofen), procedure for, 310, 313–314 indications, actions, and dosage of, Venlafaxine (Effexor), indications, 550 actions, and dosage of, 617 Vicryl Rapide (polyglycolic acid 910) Venography, peripheral, 329 sutures, 346t Venous oxygen saturation (SVO2), for Vicryl (polyglactin 910) sutures, 346t cardiac output determination, 412, Videx (didanosine), indications, actions, 413f and dosage of, 526–527 Ventilation, 414–416, 415f–417f Vinblastine (Velban; Velbe), indications, mechanical. See Mechanical ventilation actions, and dosage of, 617 Ventolin (albuterol), 364 Vincasar PFS (vincristine), indications, for anaphylaxis, 469 actions, and dosage of, 617–618 indications, actions, and dosage of, 490 Vincristine (Oncovin; Vincasar PFS), nebulized, for asthmatic attacks, 469 indications, actions, and dosage of, Ventricular arrhythmias, on 617–618 electrocardiograms, 375–377, Vinorelbine (Navelbine), indications, 376f–378f actions, and dosage of, 618 740 Index Vioxx (rofecoxib) indications, actions, and dosage of, 516 indications, actions, and dosage of, 599 intoxication by, hypercalcemia with, route, effects, and dosage for, 321t 188 Viracept (nelfinavir), indications, actions, in total parenteral nutrition, 231t and dosage of, 150t, 576 Vitamin E, in total parenteral nutrition, Viral cultures and serology, 132 231t Viral infections. See also specific Vitamin K infections indications, actions, and dosage of, 589 cerebrospinal fluid in, 287t in total parenteral nutrition, 231 pathogens and drugs of choice for Vitrasert (ganciclovir), indications, treating, 146t–149t actions, and dosage of, 146t, Viramune (nevirapine), indications, 543–544 actions, and dosage of, 577 Vitravene (fomivirsen), indications and Virazole (ribavirin), indications, actions, dosage for, 146t and dosage of, 146t, 148t, 598 Vitrobacter, Gram stain characteristics of, Virchow’s node, 27 126t Viroptic (trifluridine), indications, actions, Vivonex tubes, 273 and dosage of, 147t, 614 Voiding cystourethrography (VCUG), 329 Visceral larva migrans, drugs for treating, Voltaren (diclofenac) 154t indications, actions, and dosage of, 526 Visceral pain, 316 route, effects, and dosage for, 321t Visken (pindolol), indications, actions, Volume expanders, 484 and dosage of, 589 Volume limited ventilators, 423 Vistaril (hydroxyzine), indications, Volume overload, transfusions and, 202, actions, and dosage of, 551 203 Vistide (cidofovir), indications, actions, Vomiting, differential diagnosis of, 49 and dosage of, 146t, 516 von Graefe’s sign, 27 Visual Analogue Scale (VAS), 319 V/Q scans, 334 Vital capacity (VC), 361, 361t, 416, 416f Vumon (teniposide), indications, actions, Vitamin(s), for total parenteral nutrition, and dosage of, 607–608 231, 231t Vitamin A, in total parenteral nutrition, 231t W Vitamin B1 Warfarin (Coumadin) indications, actions, and dosage of, 609 indications, actions, and dosage of, 618 for seizures, 472 interaction with enteral nutrition, 223 in total parenteral nutrition, 231t Washed red blood cells, 197t Vitamin B6 Water balance, 177–178 indications, actions, and dosage of, 596 Water loss, hypernatremia and, 184–185 in total parenteral nutrition, 231t Waxy casts, in urine sediment, 114 Vitamin B12 Wayson stain, 128 blood level of, laboratory diagnosis and, Weaning, from mechanical ventilation, 92–93 427–429, 428t indications, actions, and dosage of, 521 Weber-Rinne test, 27 laboratory diagnosis and, 92–93 Weight conversion, 658, 658t in total parenteral nutrition, 231t Weight loss, differential diagnosis of, 52 Vitamin C, in total parenteral nutrition, Welchol (colesevelam), indications, 231t actions, and dosage of, 520 Vitamin D Wellbutrin (bupropion), indications, deficiency of, hypocalcemia and, 189 actions, and dosage of, 507 Index 741 Wellcovorin (leucovorin), indications, X-ray studies actions, and dosage of, 559 contrast, 326–329 Wenckebach heart block, 377–378, noncontrast, 325–326, 335–338 379f Xylocaine. See Lidocaine (Anestacon Westcort (hydrocortisone valerate), Topical; Xylocaine) potency and application of, 629t Xyvox (linezolid), indications, actions, Whaid’s maneuver, 280 and dosage of, 561 Wheals, 21t Wheezing, differential diagnosis of, 52 Whipple’s triad, 27 Y White blood cell(s) (WBCs) Yeast, in urine sediment, 112 differential, 96–97, 97t Yersinia enterocolitica, Gram stain morphologic changes in, 104 characteristics of, 127t three-cell differential count, 97, 100 Yersinia pestis, Gram stain characteristics transfusions of, 201 of, 127t in urine sediment, 112 White blood cell (WBC) casts, in urine sediment, 114 Z Whole blood, for transfusion, 197t Zafirlukast (Accolate), indications, Witch hazel (Tucks Pads), indications, actions, and dosage of, 619 actions, and dosage of, 618 Zalcitabine (Hivid), indications, actions, Wolff-Parkinson-White syndrome, on and dosage of, 619 electrocardiograms, 388, 388f Zaleplon (Sonata), indications, actions, Wound care, medications for, 487 and dosage of, 619 Wound healing, 345 Zanamivir (Relenza), indications, actions, Wound precautions, 155 and dosage of, 147t, 619 Wright’s stain, 95, 96 Zanosar (streptozocin), indications, Wrist, arthrocentesis of, 248, 249f actions, and dosage of, 604 Written history and physical, 5 Zantac (ranitidine) example of, 28–32 for anaphylaxis, 469 Wuchereria bancrofti infections, drugs for indications, actions, and dosage of, 597 treating, 153t Zarontin (ethosuximide) Wycillin (penicillin G procaine), half-life and therapeutic and toxic levels indications, actions, and dosage of, of, 631t 585 indications, actions, and dosage of, 536 Wytensin (guanabenz), indications, Zaroxolyn (metolazone), indications, actions, and dosage of, 546–547 actions, and dosage of, 569 Zebeta (bisoprolol), indications, actions, and dosage of, 505 X Zefazone (cefmetazole), indications, Xalatan (latanoprost), indications, actions, actions, and dosage of, 511 and dosage of, 558 Zenapax (dacliximab), indications, Xanax (alprazolam), indications, actions, actions, and dosage of, 522 and dosage of, 492 Zerit (stavudine), indications, actions, and Xanthochromia, 286 dosage of, 603 Xanthomonas maltophilia, Gram stain Zestril (lisinopril) characteristics of, 127t for emergency cardiac care, 461 Xeromammography, 326 indications, actions, and dosage of, 562 Xopenex (levalbuterol), indications, Ziagen (abacavir), indications, actions, actions, and dosage of, 559 and dosage of, 488 742 Index Zidovudine (Retrovir), indications, Zomig (zolmitriptan), indications, actions, actions, and dosage of, 619 and dosage of, 620 Zidovudine + lamivudine (Combivir), Zonalon (doxepin, topical), indications, indications, actions, and dosage of, actions, and dosage of, 531 619 Zonisamide (Zonegran), indications, Zileuton (Zyflo), indications, actions, and actions, and dosage of, 620 dosage of, 619 Zoster. See also Varicella zoster virus Zinacef (cefuroxime), indications, actions, (VZV) and dosage of, 513 drugs of choice for treating, 148t, Zinc 149t laboratory diagnosis and, 93 Zostrix (capsaicin), indications, actions, in total parenteral nutrition, 231, 232t and dosage of, 509 Zinecard (dexrazoxane), indications, Zosyn (piperacillin-tazobactam), actions, and dosage of, 525 indications, actions, and dosage of, Zithromax (azithromycin) 590 indications, actions, and dosage of, 501 Zovia 1/35E 21, 28, 624t for subacute bacterial endocarditis Zovia 1/50E 21, 28, 624t prophylaxis, 158t Zovirax (acyclovir), indications, actions, Zocor (simvastatin), indications, actions, and dosage of, 147t, 148t, 149t, and dosage of, 601 490 Zofran (ondansetron), indications, actions, Zyban (bupropion), indications, actions, and dosage of, 580–581 and dosage of, 507 Zoladex (goserelin), indications, actions, Zyflo (zileuton), indications, actions, and and dosage of, 546 dosage of, 619 Zolmitriptan (Zomig), indications, actions, Zyloprim (allopurinol), indications, and dosage of, 620 actions, and dosage of, 491 Zoloft (sertraline), indications, actions, Zyprexa (olanzapine), indications, actions, and dosage of, 601 and dosage of, 580–581 Zolpidem (Ambien), indications, actions, Zyrtec (cetirizine), indications, actions, and dosage of, 620 and dosage of, 514

Diagnosis and Treatment of Human Mycoses In f e c t i o u s D i s e a s e Series Editor: Vassil St. Georgiev National Institute of Allergy and Infectious Diseases National Institutes of Health Diagnosis and Treatment of Human Mycoses, edited by Duane R. Hospenthal, MD, PhD and Michael G. Rinaldi, PhD, 2008 Foodborne Diseases, edited by Shabbir Simjee, PhD, 2007 Reverse Transcriptase Inhibitors in HIV/AIDS Therapy, edited by Gail Skowron, MD and Richard Ogden, PhD, 2006 Vaccine Adjuvants: Immunological and Clinical Principles, edited by Charles J. Hackett, PhD and Donald A. Harn, Jr., PhD, 2006 Congenital and Perinatal Infections: A Concise Guide to Diagnosis, edited by Cecelia Hutto, MD, 2006 Drug Interactions in Infectious Diseases: Second Edition, edited by Stephen C. Piscitelli, PharmD and Keith A. Rodvold, PharmD, 2005 Biological Weapons Defense: Infectious Disease and Counterbioterrorism, edited by Luther E. Lindler, PhD, Frank J. Lebeda, PhD, and George W. Korch, PhD, 2005 Microbial Genomes, edited by Claire M. Fraser, PhD, Timothy D. Read, PhD, and Karen E. Nelson, PhD, 2004 Management of Multiple Drug-Resistant Infections, edited by Stephen H. Gillespie, MD, 2004 Aging, Immunity, and Infection, by Joseph F. Albright, PhD and Julia W. Albright, PhD, 2003 Handbook of Cytokines and Chemokines in Infectious Diseases, edited by Malak Kotb, PhD and Thierry Calandra, MD, PhD, 2003 Opportunistic Infections: Treatment and Prophylaxis, Vassil St. Georgiev, PhD, 2003 Innate Immunity, edited by R. Alan B. Ezekowitz, MBChB, DPhil, FAAP, and Jules A. Hoffmann, PhD, 2003 Pathogen Genomics: Impact on Human Health, edited by Karen Joy Shaw, PhD, 2002 Immunotherapy for Infectious Diseases, edited by Jeffrey M. Jacobson, MD, 2002 Retroviral Immunology: Immune Response and Restoration, edited by Giuseppe Pantaleo, MD and Bruce D. Walker, MD, 2001 I n f e c t i o u s D i s e a s e Diagnosis and Treatment of Human Mycoses Edited by Duane R. Hospenthal, MD, PhD Infectious Disease Service, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX; F. Edward Hébert School of Medicine, Uniformed Services University of Health Sciences, Bethesda, MD Michael G. Rinaldi, PhD Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX © 2008 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 All rights reserved. www.humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. The content and opinions expressed in this book are the sole work of the authors and editors, who have warranted due diligence in the creation and issuance of their work. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences arising from the information or opinions presented in this book and make no warranty, express or implied, with respect to its contents. Due diligence has been taken by the publishers, editors, and authors of this book to assure the accuracy of the information published and to describe generally accepted practices. The contributors herein have carefully checked to ensure that the drug selections and dosages set forth in this text are accurate and in accord with the standards accepted at the time of publication. Notwithstanding, since new research, changes in government regulations, and knowledge from clinical experience relating to drug therapy and drug reactions constantly occur, the reader is advised to check the product information provided by the manufacturer of each drug for any change in dosages or for additional warnings and contraindications. This is of utmost importance when the recommended drug herein is a new or infrequently used drug. It is the responsibility of the treating physician to determine dosages and treatment strategies for individual patients. Further, it is the responsibility of the health care provider to ascertain the Food and Drug Administration status of each drug or device used in their clinical practice. The publishers, editors, and authors are not responsible for errors or omissions or for any consequences from the application of the information presented in this book and make no warranty, express or implied, with respect to the contents in this publication. This publication is printed on acid-free paper. ∞ ANSI Z39.48-1984 (American Standards Institute) Permanence of Paper for Printed Library Materials Cover design by Karen Schulz Cover illustration: Septate, uniform hyphae of Aspergillus fumigatus (see Color plate 1, following p. 48). For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel.: 973-256-1699; Fax: 973-256-8341; or visit our Website: www.humanapress.com Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Humana Press Inc., provided that the base fee of US $30.00 per copy is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Humana Press Inc. The fee code for users of the Transactional Reporting Service is: [978-1-58829-822-5/08 $30.00]. e-ISBN 978-1-59745-325-7 Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 Library of Congress Control Number: 2007929353 Preface With the rapid expansion of medical technologies and treatments over the past several decades fungi have emerged as important causative agents of human infection (mycosis). Improved survival afforded by cancer and human immunodeficiency virus (HIV) therapies, intensive care units, and broad-spectrum antibacterial agents continue to increase the population at risk for these infections. Fortunately, our understanding of the fungi, and ability to diagnose and treat fungal infections, has also progressed over this time. Diagnosis and Treatment of Human Mycoses brings together globally recognized mycoses experts to guide readers in the use of the current knowledge in the field of medical mycology to manage those who suffer from fungal infections (mycoses). Diagnostic strategies and tests, including basic and directed culturing techniques, histopathology with standard and special stains, serological methods, and radiological studies, often all need to be considered and commonly combined to make the diagnosis of fungal infection. This book introduces and reviews these tools first separately and later as they pertain to specific infections or groups of diseases. The antifungal armamentarium has almost exponentially expanded over the past decade alone. In addition to amphotericin B, multiple systemically active triazole and echinocandin antifungal agents are now available. Selecting which drug to use has now progressed beyond amphotericin B or no amphotericin B, allowing many options for therapy, but also increasing the complexity of choosing which agent to employ. With the differing spectrums of these agents, diagnosis to species level has become more necessary to provide the best care to those infected. This expansion and increases in disease also raises questions of prophylactic therapy and preemptive and combination use of these drugs. The development of standardized antifungal susceptibility testing promises to help with questions of selecting the best antifungal for individual patients, but has also introduced questions of how and when to best use this still emerging technology. Diagnosis and Treatment of Human Mycoses is meant to be a concise text that will provide the busy infectious disease, hematology–oncology, pulmonology, or critical care specialist a practical tool to diagnose and manage fungal infections. In addition, the depth of the material in the text will provide these and other medical specialists and trainees an excellent reference and learning resource. The text is divided into four parts to guide the reader. Part I gives a general introduction with epidemiology and presents practical approaches for using patient risk factors, exposures, and site of infection to direct diagnostic evaluations. Part II introduces the science of mycology and the current tools available to diagnose fungal infections, in the clinical mycology laboratory, using histopathology and diagnostic immunology, and with radiological technologies. Part III provides an in-depth review v vi Preface of the available antifungal drugs, their use, and discussion of resistance and antifungal susceptibility testing. After the reader is provided with the overview of diagnostic and therapeutic tools in Parts I to III, Part IV presents the human mycoses in 15 uniform, easy to read chapters, with accompanying tables and figures. At the end of the text are 18 instructive cases that provide the reader a review of many of the important concepts presented in the book. Each case is presented as an unknown to test the knowledge obtained or to emphasize an important or complex subject in the field. Duane R. Hospenthal, MD, PhD Michael G. Rinaldi, PhD The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government. Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Color Plates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii Companion CD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv Part I: Approach to Patients 1 Approach to Patients with Suspected Fungal Infections Clinton K. Murray and Duane R. Hospenthal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Part II: Laboratory and Radiological Diagnosis 2 Basic Mycology Deanna A. Sutton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 3 Diagnostic Histopathology Michael B. Smith and Michael R. McGinnis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 4 Diagnostic Immunology Samit S. Desai and Brian Wong. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 5 Diagnostic Radiology Maria Angela C. Hospenthal and Constanza J. Gutierrez . . . . . . . . . . . . . . . . . 81 Part III: Antifungal Agents 6 Antifungal Agents Russell E. Lewis and Annette W. Fothergill . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 Part IV: Mycoses 7 Candidiasis Jack D. Sobel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 8 Infection Due to Non-Candidal Yeasts Jose A. Vazquez . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 9 Aspergillosis Helen W. Boucher and Thomas F. Patterson . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 10 Hyalohyphomycosis—Infection Due to Hyaline Moulds Rhonda V. Fleming and Elias J. Anaissie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 vii viii Contents 11 Phaeohyphomycosis—Infection Due to Dark (Dematiaceous) Moulds Sanjay G. Revankar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 12 Zygomycosis (Mucormycosis) Charalampos Antachopoulos, Juan C. Gea-Banacloche and Thomas J. Walsh . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227 13 Pneumocystosis Francis Gigliotti and Terry W. Wright . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245 14 Cryptococcosis Methee Chayakulkeeree and John R. Perfect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255 15 Blastomycosis Stanley W. Chapman and Donna C. Sullivan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277 16 Coccidioidomycosis Royce H. Johnson and Shehla Baqi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295 17 Histoplasmosis L. Joseph Wheat and Nicholas G. Conger . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317 18 Paracoccidioidomycosis Angela Restrepo, Angela M. Tobón and Carlos A. Agudelo . . . . . . . . . . . . . . . . 331 19 Sporotrichosis Carol A. Kauffman . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343 20 Dermatophytosis (Tinea) and Other Superficial Fungal Infections Aditya K. Gupta and Elizabeth A. Cooper . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355 21 Subcutaneous Fungal Infections (Chromoblastomycosis, Mycetoma, and Lobomycosis) Michael B. Smith and Michael R. McGinnis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383 Instructive Cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393 Instructive Cases Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423 Contributors Carlos A. Agudelo, md • Facultad de Medicina, Universidad Pontificia Bolivariana, Medellín, Colombia Elias J. Anaissie, md • Myeloma Institute for Research and Therapy, Division of Cancer Supportive Care, University of Arkansas for Medical Sciences, Little Rock, AR Charalampos Antachopoulos, md • Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD Shehla Baqi, md • Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at the University of California at Los Angeles; and Department of Medicine, Kern Medical Center, Bakersfield, CA Helen W. Boucher, md • Division of Infectious Diseases, Department of Medicine, Tufts University–New England Medical Center, Boston, MA Stanley W. Chapman, md • Division of Infectious Diseases, Department of Medicine, University of Mississippi Medical Center, Jackson, MS Methee Chayakulkeeree, md • Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC Nicholas G. Conger, md • Division of Infectious Diseases, Landstuhl Regional Medical Center, Landstuhl Germany Elizabeth A. Cooper, hbsc • Mediprobe Research Inc., London, Ontario, Canada Samit S. Desai, md • Infectious Diseases Section, Yale University School of Medicine, New Haven; and Infectious Diseases Section, Veterans Affairs Connecticut Healthcare System, West Haven, CT Rhonda V. Fleming, md • Division of Infectious Diseases, Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX Annette W. Fothergill, ma, mba • Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX Juan C. Gea-Banacloche, md • Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD Francis Gigliotti, md • Division of Infectious Diseases, Department of Pediatrics; and Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY Aditya K. Gupta, md, phd • Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Center, Toronto; University of Toronto, Toronto; and Mediprobe Research, Inc., London, Ontario, Canada ix x Contributors Constanza J. Gutierrez, md • Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX Duane R. Hospenthal, md, phd • Infectious Disease Service, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX; F. Edward Hébert School of Medicine, Uniformed Services University of Health Sciences, Bethesda, MD Maria Angela C. Hospenthal, md • Division of Pulmonary/Critical Care Medicine, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX Royce H. Johnson, md • Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at the University of California at Los Angeles; and Department of Medicine, Kern Medical Center, Bakersfield, CA Carol A. Kauffman, md • Division of Infectious Diseases, University of Michigan Medical School and Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI Russell E. Lewis, pharmd • University of Houston College of Pharmacy, Houston, TX Michael R. McGinnis, phd • Department of Pathology; and Medical Mycology Research Center, University of Texas Medical Branch, Galveston, TX Clinton K. Murray, md • Infectious Disease Service, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX; F. Edward Hébert School of Medicine, Uniformed Services University of Health Sciences, Bethesda, MD Thomas F. Patterson, md • Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at San Antonio; and Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, TX John R. Perfect, md • Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC Angela Restrepo, phd • Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia Sanjay G. Revankar, md • Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI Michael G. Rinaldi, phd • Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX Michael B. Smith, md • Department of Pathology, University of Texas Medical Branch, Galveston, TX Jack D. Sobel, md • Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI Donna C. Sullivan, phd • Division of Infectious Diseases, Department of Medicine, University of Mississippi Medical Center, Jackson, MS Deanna A. Sutton, phd • Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX Angela M. Tobón, md • Corporación para Investigaciones Biológicas (CIB); Facultad de Medicina, Universidad Pontificia Bolivariana; and Hospital La María, Medellín, Colombia Contributors xi Jose A. Vazquez, md • Division of Infectious Diseases, Henry Ford Hospital; and Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI Thomas J. Walsh, md • Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD L. Joseph Wheat, md • MiraVista Diagnostics and Mirabella Technologies, Indianapolis, IN Brian Wong, md • Division of Infectious Diseases, Department of Medicine, Oregon Health and Science University, Portland, OR Terry W. Wright, phd • Division of Infectious Diseases, Department of Pediatrics; and Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY Color Plates Color Plates follow p. 48 Color Plate 1 Fig. 1, Chapter 3: Septate, uniform hyphae of Aspergillus fumigatus. Hyphae morphology is characteristic but not specific. GMS. See discussion on p. 37. Color Plate 2 Fig. 2, Chapter 3: Uniform, yeast-like cells in chains of Lacazia loboi. GMS. (Photo courtesy of Dr. A. Padhye). See discussion on p. 37. Color Plate 3 Fig. 3, Chapter 3: Large sporangium containing sporangiospores and smaller trophocytes of Rhinosporidium seeberi. PAS. See discussion on p. 37. Color Plate 4 Fig. 4, Chapter 3: Mucicarmine stain demonstrating positive staining of capsule of Cryptococcus neoformans. Mayer’s mucicarmine. See discussion on pp. 37, 41. Color Plate 5 Fig. 5, Chapter 3: Pigmented brown sclerotic bodies seen in a case of chromoblastomycosis. The pigment would be masked in a GMS stain. H&E. See discussion on p. 41. Color Plate 6 Fig. 6, Chapter 3: Small intracellular yeast with budding, charac- teristic of Histoplasma capsulatum. GMS. See discussion on p. 42. Color Plate 7 Fig. 7, Chapter 3: Penicillium marneffei. Yeast showing occasional transverse septa (center). Note absence of budding. GMS. See discussion on p. 42. Color Plate 8 Fig. 8, Chapter 3: Broad-based budding of Blastomyces dermatitidis in a background of neutrophils and histiocytes. H&E. See discussion on p. 44. Color Plate 9 Fig. 9, Chapter 3: Large spherule containing endospores of Coccid- ioides species. H&E. See discussion on p. 44. Color

Plate 10 Fig. 10, Chapter 3: Sporothrix schenckii with characteristic “cigar- shaped” buds attached by narrow base to the parent cell. GMS. See discussion on pp. 44, 45. Color Plate 11 Fig. 11, Chapter 3: Hyphae of a Zygomycete. H&E. See discussion on p. 46. Color Plate 12 Fig. 12, Chapter 3: Hyphae of Aspergillus terreus with small, lateral aleurioconidia. GMS. See discussion on p. 46. xiii Companion CD Color versions of illustrations listed here may be found on the Companion CD attached to the inside back cover. The image files are organized into folders by chapter number and are viewable in most Web browsers. The number following “f ” at the end of the file name identifies the corresponding figure in the text. The CD is compatible with both Mac and PC operating systems. Chapter 2 Figs. 1–16 Chapter 3 Figs. 1–12 Chapter 6 Figs. 2–4 and 6 Chapter 8 Fig. 1 Chapter 9 Figs. 1 and 2 Chapter 10 Fig. 1 Chapter 11 Figs. 2 and 3 Chapter 12 Figs. 1, 2 and 3 Chapter 13 Fig. 1 Chapter 14 Figs. 4–7 Chapter 15 Figs. 1, 7 and 8 Chapter 16 Figs. 6–9 Chapter 17 Figs. 1, 2 and 6 Chapter 18 Figs. 1, 2 and 4–6 Chapter 19 Figs. 1–5 Chapter 20 Figs. 1–12 Chapter 21 Figs. 1–4 Instructive Case: Figs. 1–5, 7, 10, 12–14 and 17 xv I Approach to Patients 1 Approach to Patients with Suspected Fungal Infections Clinton K. Murray, MD and Duane R. Hospenthal, MD, PhD 1. INTRODUCTION The incidence of fungal infections (mycoses) is increasing throughout the world as a result of modern medical advances that use immunosuppressive therapies, broad- spectrum antibiotics, and central venous access devices, as well as a rise in the population of individuals at risk. Technology has led to the improved survival of persons with malignancies, transplanted organs, and human immunodeficiency virus (HIV) infection; those who have experienced trauma; and persons at the extremes of age. The medical community has met this challenge with the introduction of new antifungal agents, often with less toxicity and improved spectrums of activity. In addition, newer, more sensitive and specific diagnostic strategies such as improved radiographic imaging and serological tests have provided clinicians with better tools to detect fungal infections earlier, potentially influencing disease outcomes. Despite these advances, the approach to the diagnosis and management of fungal infections still relies on recognizing the interaction of the pathogen and the host. Although some fungal diseases have classic presentations, many of these occur so rarely that clinicians may not initially include them in their differential diagnoses. In the setting of immuno- suppression, mycoses may produce nonspecific signs and symptoms, making their diagnosis a challenge. Early recognition and treatment are fundamental to modifying disease outcomes in many fungal infections, especially those in immunocompromised individuals. Increased awareness of key risk factors and clinical presentations of the human mycoses may enable clinicians to develop an inclusive approach to the diagnosis of these diseases. The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government. The authors are employees of the US government. This work was prepared as part of their official duties and, as such, there is no copyright to be transferred. From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 3 4 Clinton K. Murray and Duane R. Hospenthal 2. EPIDEMIOLOGY Deaths associated with mycoses have increased in the United States, advancing from the 10th most common infectious disease cause of death in 1980 to the 7th in 1997 (1). Sepsis due to fungal infection increased more than 200% in the United States between 1979 and 2000 (2). Fungal sepsis is chiefly secondary to infection with Candida, which continues to be the fourth most common organism recovered from bloodstream infections in the United States, associated with an estimated mortality of about 40% (3,4). Candidemia and disseminated (also termed systemic or invasive) candidiasis continue to be the most common nosocomial fungal infections, responsible for more than 80% of these infections and up to 15% of nosocomial infections overall. Infections with Candida have declined in patients with cancer and in those undergoing hematopoietic stem cell transplantation (HSCT), likely in association with antifungal prophylaxis. The incidence of candidemia, after surging in the 1980s, appears to have declined, at least in the intensive care setting (5). This overall decline is chiefly due to fewer infections with C. albicans, as non-albicans Candida (NAC) candidemia has increased over this same period, 1989–1999. The range of hosts who develop opportunistic mould infections, most commonly caused by the Aspergillus species, continues to expand from severely neutropenic cancer patients to patients with other risk factors, including persons with prolonged immunosuppressive therapies with corticosteroids and newer agents, including those that inhibit tumor necrosis factor-alpha (TNF-) (6). Aspergillus is the second most common cause of nosocomial fungal infection and the most common mould to cause invasive mycosis. Other rare opportunistic moulds (e.g., the zygomycetes, Fusarium, and Scedosporium) and yeasts (e.g., Trichosporon and Malassezia) have emerged as more frequent causes of disease in patients with a wide range of risks (7–13). Outbreaks of endemic mycoses, including coccidioidomycosis in association with the growing urbanization of the US Southwest, and on a smaller scale, histoplas- mosis, continue to be reported more frequently, often affecting greater numbers of persons. Outbreaks of endemic disease are occasionally diagnosed outside their known geographical areas, occurring in travelers to those locales. A localized outbreak of infection with the non-neoformans Cryptococcus, C. gattii, in immunocompetent patients has recently been reported in southwest Canada (Vancouver Island) (14). 3. SUSPICION BASED ON RISK FACTORS The risks for fungal infections are highly dependent on the combination of host immune competency and the specific exposures people have both within the healthcare system and in their communities. 3.1. Immunocompromise Host immune status is probably the most important underlying factor determining whether people develop life-threatening, self-limiting, or no infection after exposure to fungi in their environment. Defense against invasive mycoses depends chiefly on intact mucosal barriers, the innate immunity provided by phagocytic cells, and cell-mediated immunity (CMI). The impact of humoral immunity appears limited and remains poorly defined in defense against the fungi. 1. Approach to Suspected Fungal Infections 5 3.1.1. Neutropenia and Altered Phagocytic Function Classically, neutropenia has been associated with candidemia and invasive candidiasis. With prolonged neutropenia, Aspergillus species become more common causes of infection. Infection with the zygomycetes, Fusarium, Scedosporium, Trichosporon, and other rare species can also been seen with prolonged loss of neutrophils. The incidence of candidiasis in the highest risk populations appears to have declined over the past decade in association with antifungal prophylaxis of these patients. This decrease has been associated with an increase in aspergillosis and other invasive mould infections. In addition to insufficient numbers of neutrophils, decline in phagocytic function also raises the risk of mycoses. The phagocytic dysfunction seen in chronic granulomatous disease (CGD) is associated with fungal infections, especially aspergillosis. 3.1.2. Impaired Cell-Mediated Immunity Impaired CMI occurs in patients infected with HIV and in those receiving many of the currently used immunosuppressive therapies. Impairment of CMI is associated with mucocutaneous candidiasis, Pneumocystis pneumonia, infection with Crypto- coccus, and more severe and/or disseminated endemic mycoses. The specific mycoses associated with CD4+ T lymphocyte decline as seen in HIV/AIDS have been carefully documented, allowing the clinician to increase the level of suspicion for particular fungal infections based on CD4+ T lymphocyte counts of their patients (Table 1.1). 3.1.3. Organ Transplantation Solid organ and HSCT recipients are at great risk for fungal infections (15–17). In addition to immunosuppressive therapies, the mucosal damage and intensive therapy associated with these procedures place the persons who receive them at risk for the entire spectrum of fungal disease. Transplant medicine has seen substantial advance- ments in tailoring regimens to minimize the duration of neutropenia and to reduce immunosuppressive treatments used to control rejection. Unfortunately, most of these still place patients at a substantial risk for opportunistic infections. In solid organ transplantation, the risk of fungal infection is associated with risk surrounding the initial surgery and the use of immunosuppression to prevent rejection. This risk varies greatly based on the organ transplanted and underlying condition of the recipient. As Table 1.1 Mycoses commonly associated with HIV infection CD4+ T lymphocyte cell count (cells/μl) Fungal infections >500 Candidal vaginitis 200–500 Thrush (oropharyngeal candidiasis) <200 PCP, disseminated histoplasmosis, disseminated coccidioidomycosis <100 Cryptococcosis, candidal esophagitis, penicilliosis PCP, Pneumocystis pneumonia. 6 Clinton K. Murray and Duane R. Hospenthal an example, in liver transplantation the substantial risk of Candida infection in the first month is associated mostly with surgical manipulation of the gastrointestinal tract and need for intensive care monitoring, as well as initial immunosuppressive agents given to control rejection (Table 1.2). Lung transplants are at high risk for invasive pulmonary aspergillosis, likely secondary to the route of inoculation and immuno- suppression. Although a similar sequence of occurrence of fungal infection is seen in HSCT, the underlying factors creating risk differ from those of solid organ trans- plant (Table 1.3). In HSCT, initial conditioning commonly leads to neutropenia and breakdown of the mucosal surfaces. This neutropenia can be prolonged and associated with life-threatening mould infections. In allogeneic HSCT, graft versus host disease (GvHD) and its treatment may put the patient at risk for fungal infection for a prolonged period of time after engraftment. 3.2. Healthcare Exposure (Nosocomial) A multitude of risk factors for nosocomial fungal infections have been identified (Table 1.4) (6,18,19). Unfortunately, many of these healthcare-associated risk factors overlap with those associated with bacterial infections or are risks that are common to many or most hospitalized patients. This is especially true for patients hospi- talized in intensive care units, the majority of whom have central venous catheters and are receiving broad-spectrum antibiotics (20,21). In addition to the use of vascular catheters, other procedures including urinary catheterization and intubation establish portals of entry for fungal pathogens. Other risk factors include immunosuppression seen with the use of corticosteroids and chemotherapy, malnutrition and malignancy. Table 1.2 Fungi associated with solid organ transplantation Time period Common fungi Other fungi First month Candida 1–6 months Aspergillus, Pneumocystis, Cryptococcus Endemic fungia >6 months Endemic fungia Cryptococcus aChiefly, Coccidioides and Histoplasma. Table produced from data in ref. 16. Table 1.3 Fungi associated with hematopoietic stem cell transplantation Time period Common fungi Other fungi Preengraftment (<30 days) Candida Aspergillus Postengraphment Aspergillus,Candida, Zygomycetes, Fusarium, (30–100 days) Pneumocystis Pseudallescheria (Scedosporium) Late (>100 days) Aspergillus, Pneumocystis Table produced from data in ref. 15. 1. Approach to Suspected Fungal Infections 7 Table 1.4 Risk factors commonly associated with healthcare-associated invasive mycoses Mycosis Risk factors Candidiasis Candida colonization, surgery (especially abdominal), acute renal failure, parenteral nutrition, central venous catheters, neutropenia, broad spectrum antibacterial antimicrobials, mucosal surface disruption Aspergillosis Prolonged neutropenia, corticosteroids, neutrophil dysfunction, hematologic malignancy, cytotoxic drugs, AIDS, HSCT (highest in allogeneic), solid organ transplantation (highest heart-lung), underlying lung disease, GvHD, GvHD therapies (TNF- blockers) HSCT, hematopoietic stem cell transplantation; GvHD, graft versus host disease; TNF-, tumor necrosis factor alpha. Infusion of contaminated infusates, inclusion of lipids in parenteral nutrition, and construction within the hospital are additional exposures that can lead to fungal infec- tions. A few specific risks allow the clinician to suspect certain fungi. Ketoacidosis and deferoxamine therapy has been clearly shown to be a risk for zygomycosis (mucormycosis). Unfortunately, given the overlapping nature of most of these risk factors with those associated with bacterial infections, it is often difficult to apply these risk factors to differentiate patients at higher risk of fungal versus bacterial infection. 3.3. Community Exposure The fungi that cause community-acquired infections commonly originate in the environment and are “true pathogens,” that is, cause disease in persons with normal immune status. Most are restricted to certain geographic environments or exposure risks (Table 1.5). The sources of disease include inhalation, ingestion, or traumatic inoculation of the fungi. Diseases most commonly afflict the lungs, paranasal sinuses, skin, and soft tissues. Rarely, disseminated, central nervous system, or osteoarticular disease occurs. The most commonly recognized community-acquired infections are the endemic mycoses, each with their limited geographical areas of exposure. With the extensive use of antibiotics, corticosteroids, and other immune

modulators in the community, as well as the increased number of elderly and populations of immunocom- promised persons receiving their care outside of the hospital, the boundaries between community-acquired and healthcare-associated infection have become blurred. 3.4. Other Risks Other risks or probable risks associated with immune competency or genetic dispo- sition include gender and race. The role of gender, and potentially inhibitory effect of estrogen, has been postulated to be important in the risk of clinical paracoccidioidomy- cosis. A clear risk for disseminated coccidioidomycosis has been seen in women when disease is acquired in pregnancy. Disseminated and severe coccidioidomycosis has also been associated with Filipino and African descent. Table 1.5 Geographic areas in which the endemic mycoses reside Mycosis Region Specific countries/areas with Associated exposure risksa increased prevalence Blastomycosis North Americab Southeastern and south central Soil exposure near fresh water (fishing, United States, Canada hunting, farming, construction) Coccidioidomycosis Western Hemisphere Southwestern United States, Soil/dust exposure (construction, archeology) Central and South America Histoplasmosis Worldwide Mississippi and Ohio River Soil or organic material associated with bird or bat valleys, Western Africa guano (construction, demolition, spelunking) Paracoccidioidomycosis Latin America Brazil, Columbia, Venezuela, Farming or other outdoor employment Ecuador, Argentina Penicilliosisc Southeast Asia China, Northeast India, Taiwan, Rice farming, rodent burrows Thailand, Vietnam Sporotrichosis Worldwide North America, Japan Gardening, sphagnum moss, hay, roses/thorns aNot all well-proven. bRare reports from Africa, Central and South America, India, and the Middle East. cRestricted almost exclusively to persons with AIDS. Table 1.6 Mycosis by organ system chiefly affected Focus of disease on presentation Community-associated fungi Healthcare-associated fungi Pulmonary Blastomyces, Coccidioides, Histoplasma, Aspergillus, zygomycetes, Pseudallescheria Paracoccidioides (Scedosporium),Fusarium, Cryptococcus, Pneumocystis Superficial/cutaneous/subcutaneous Dermatophytes (Trichophyton, Candida, Fusarium, Trichosporon Microsporum, Epidermophyton), Candida, Malassezia, agents of mycetoma, agents of chromblastomycosis, Blastomyces, Paracoccidioides, Cryptococcus, Sporothrix, zygomycetes, phaeohyphomycetes, Lacazia Bone and joint Blastomyces, Coccidioides, Histoplasma, Candida, Cryptococcus Paracoccidioides, Sporothrix Central nervous system Cryptococcus, Coccidioides, Blastomyces, Aspergillus, Candida Histoplasma, phaeohyphomycetes, Pseudallescheria (Scedosporium) Genitourinary Blastomyces, Coccidioides, Histoplasma Candida, Trichosporon Oral Histoplasma, Paracoccidioides, Candida Candida Eye Keratitis—Candida, Aspergillus, Endophthalmitis/retinitis—Candida Fusarium, phaeohyphomycetes, other hyalohyphomycetes Disseminated disease Coccidioides, Histoplasma, Candida, Aspergillus, Fusarium, zygomycetes, Paracoccidioides, Penicillium marneffei Cryptococcus, Trichosporon and other rare yeasts 10 Clinton K. Murray and Duane R. Hospenthal The use of antifungal therapy or prophylaxis in populations at risk should also be kept in mind when evaluating patients for potential fungal infections. The last decade has seen an emergence of NAC, non-fumigatus Aspergillus infections, and increased numbers of infections with the more rare yeasts and moulds. This shift appears to reflect our greater use of antifungals and the newer agents. Included in this change in epidemiology is the emergence of fluconazole-resistant Candida (i.e., C. krusei) and the recent increase in non-Aspergillus moulds (e.g., the zygomycetes, Fusarium, and Scedosporium) that have decreased susceptibility or resistance to many of the currently available antifungal agents. 4. SUSPICION BASED ON ORGANS INVOLVED Although the fungi may and often do cause disease in more than one organ system, many of these are associated with certain organ system infections. The presentation of disease (e.g., prolonged or chronic pneumonia with lymphadenopathy on chest radiography) can guide the clinician to the diagnosis. Disease localization and presen- tation can be altered based on the host immune system, route of pathogen inoculation (e.g., inhalation, cutaneous inoculation, ingestion), and quantity of inoculum. The most common presentations are pulmonary, cutaneous/subcutaneous, and disseminated diseases (Table 1.6). Other presentations include those localized or involving the central nervous system, bones, joints, genitourinary tract, oral cavity, eyes, or gastroin- testinal tract. Fungal infection can affect any organ or system, often after asymptomatic respiratory system colonization and dissemination. The fungus recovered at a specific site may portend varying diagnoses based on the combination of fungus and site, often modified by patient immune status. Oral lesions in histoplasmosis or paracoc- cidioidomycosis typically indicate the presence of disseminated disease. Oral lesions from Candida in a patient recently given a short course of corticosteroids likely only indicate mild, transient, localized disease. REFERENCES 1. McNeil MM, Nash SL, Hajjeh RA, et al. Trends in the mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 2001;33:641–647. 2. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546–1554. 3. Edmund MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 1999;29:239–244. 4. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004;39:309–317. 5. Trick WE, Fridkin SK, Edwards JR, Hajjeh RA, Gaynes RP, National Nosocomial Infec- tions Surveillance System hospitals. Secular trends in hospital-acquired candidemia among intensive care unit patients in the United States during 1989–1999. Clin Infect Dis 2002;35:627–630. 6. Cornillet A, Camus C, Nimubona S, et al. Comparison of epidemiological, clinical, and biological features in invasive aspergillosis in neutropenic and nonneutropenic patients: a 6-year survey. Clin Infect Dis 2006;43:577–584. 1. Approach to Suspected Fungal Infections 11 7. Chamilos G, Luna M, Lewis RE, et al. Invasive fungal infections in patients with hemato- logic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989–2003). Haematologica 2006;91:986–989. 8. Husain S, Alexander BD, Munoz P, et al. Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi. Clin Infect Dis 2003;37:221–229. 9. Jahagirdar BN, Morrison VA. Emerging fungal pathogens in patients with hematologic malignancies and marrow/stem-cell transplant recipients. Semin Respir Infect 2002;17: 113–120. 10. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002;34:909–917. 11. Nucci M, Marr KA. Emerging fungal diseases. Clin Infect Dis 2005;41:521–526. 12. Patterson TF. Advances and challenges in management of invasive mycoses. Lancet 2005;366:1013–1025. 13. Walsh TJ, Groll A, Hiemenz J, Fleming R, Roilides E, Anaissie E. Infection due to emerging and uncommon MEDICALLY important fungal pathogens. Clin Microbiol Infect 2004;10 (Suppl 1): 48–66. 14. Hoang LMN, Maguire JA, Doyle P, Fyfe M, Roscoe DL. Cryptococcus neoformans infections at Vancouver Hospital and Health Sciences Centre (1997–2002): epidemiology, microbiology and histopathology. J Med Microbiol 2004;53:935–940. 15. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infec- tions among hematopoietic stem cell transplant recipients. MMWR 2000;49(RR-10):1–125. 16. Fishman JA, Rubin RH. Infection in organ-transplant recipients. New Engl J Med 1998– 338:1741–1751. 17. Singh N. Fungal infections in the recipients of solid organ transplantation. Infect Dis N Am 2003;17:113–134. 18. Enoch DA, Ludlam HA, Brown NM. Invasive fungal infections: a review of epidemiology and management options. J Med Microbiol 2006;55:809–818. 19. Fridkin SK. The changing face of fungal infections in health care settings. Clin Infect Dis 2005;41:1455–1460. 20. Eggimann P, Garbino J, Pittet D. Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis 2003;3:685–702. 21. Blumberg HM, Jarvis WR, Soucie JM, et al. Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. Clin Infect Dis 2001;33:177–186. SUGGESTED READINGS Clark TA, Hajjeh RA. Recent trends in the epidemiology of invasive mycoses. Curr Opin Infect Dis 2002;15:569–574. Enoch DA, Ludlam HA, Brown NM. Invasive fungal infections: a review of epidemiology and management options. J Med Microbiol 2006;55:809–818. Fridkin SK. The changing face of fungal infections in health care settings. Clin Infect Dis 2005;41:1455–1460. Husain S, Alexander BD, Munoz P, et al. Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi. Clin Infect Dis 2003;37:221–229. Walsh TJ, Groll A, Hiemenz J, Fleming R, Roilides E, Anaissie E. Infection due to emerging and uncommon medically important fungal pathogens. Clin Microbiol Infect 2004;10 (Suppl 1): 48–66. 12 Clinton K. Murray and Duane R. Hospenthal OTHER KEY RESOURCES Anaissie EJ, McGinnis MR, Pfaller MA, eds. Clinical mycology. Philadelphia: Churchill Living- stone, 2003:1–608. Dismukes WE, Pappas PG, Sobel JD, eds. Clinical mycology. New York: Oxford University Press, 2003:1–519. Kwon-Chung KJ, Bennett JE. Medical mycology. Malvern, PA: Lea & Febiger, 1992:1–866. Section G. Mycoses. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 6th ed. Philadelphia: Elsevier Churchill Living- stone, 2005:2935–3094. www.doctorfungus.org is an excellent Internet resource for information about current taxonomy and other quick reference material. II Laboratory and Radiological Diagnosis 2 Basic Mycology Deanna A. Sutton, PhD 1. INTRODUCTION The mycology laboratory plays a vital role in the diagnosis of fungal infections by recovery of the etiologic agent. Specimen collection from appropriate sites is critical, as is the proper transport, storage, and processing of samples. Fungal elements seen via direct microscopy often provide the first clues to a fungal infection, and are the basis on which empiric therapy is initiated. To ensure recovery of the fungus, a sufficient number and type of media should be utilized for primary isolation based on the clinical history and any possible organisms being expected. Accurate fungal identification, in combi- nation with antifungal susceptibility testing, provides the basis for appropriate organism- directed antifungal therapy and is essential for conducting epidemiologic investigations. Human and/or animal pathogens historically considered to be fungal are now placed in three kingdoms: Fungi, Straminipila, and Protoctista, with the bulk of the human pathogens in the kingdom Fungi (1). Organisms within this kingdom are eukaryotic (have cells containing a membrane-bound nucleus); heterotrophic (lack chlorophyll or other pigments capable of photosynthesis for making food and therefore must obtain nourishment from an external food source); may be unicellular or filamentous; and have cells surrounded by cell walls containing glucan, chitin, or both. Unlike animals, fungi possess cell walls, but unlike in plants, the major cell wall component is not cellulose. In the past, medical problems attributed to these organisms, in comparison to those caused by the bacteria, viruses, and parasites, have been relatively few, and included allergic symptoms, mushroom poisoning, mycotoxicoses from ingested fungal toxins, and occasional fungal infections (2). Fungal infections (mycoses) have increased over the past decades, with the advent of modern medical advances utilizing immunosup- pressive regimens, and with an increase in diseases/underlying conditions significantly altering the human immune system. The recovery of these organisms from host tissue and their identification is often critical to the diagnosis and treatment of mycotic disease and is the classic method for documentation of pathogenicity. Histopathology, and other adjunctive tools such as antigen or antibody assays and molecular techniques, addressed elsewhere in this text, may also be relied on for empiric/preemptive thera- peutic decisions, when cultures are either not available or fail to provide unequivocal From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 15 16 Deanna A. Sutton information. The proper collection, transport, and processing of specimens; selection of fungal stains and preliminary direct microscopy techniques; and use of appropriate media and incubation conditions are all important to the accurate identification of fungal infection. This chapter provides a cursory review of the laboratory fundamentals as they relate to medical mycology. It also reviews basic taxonomy, classification, and nomen- clature regarding the kingdom Fungi, and a description of mycologic terms/features common to the most frequently recovered etiologic agents in the teleomorphic (sexual) phyla Ascomycota, Basidiomycota, Zygomycota, and in the anamorphic (asexual) fungi. Fungi without known sexual states are referred to as “mitosporic” (based on their reproductive mitotic processes). The mitosporic fungi are the most common etiologic agents of human and animal disease. 2. SPECIMEN COLLECTION, TRANSPORT, AND PROCESSING The likelihood of recovering a fungal etiologic agent is directly proportional to the quality of methods employed in the collection, transport, and processing of clinical specimens. For all disease processes, recovery is highest from an active site of infection. Common (but not all-inclusive) specimen types include those from the respiratory tract (3), draining sites, aspirated abscess fluids, normally sterile body fluids, urine (4), vaginal secretions (5), corneal scrapings (6), surgical tissue specimens, intravenous catheter tips (obtained by the Maki roll method (7)), and various surgically removed medical devices (8). Although tissue may be homogenized for the recovery of Histo- plasma capsulatum, when the patient history suggests infection with a zygomycete or other filamentous fungi, tissue grinding should be avoided because it may be delete- rious to the growth in

culture of fragile fungal hyphae (8). Specimens peripheral to the site of infection, such as blood or bone marrow, may be diagnostic in dissemi- nated disease or when foci are not easily accessible. Several blood culture systems reliably recover yeast pathogens. If manual blood cultures are used, a broth/agar biphasic system in which an agar paddle it attached to the bottle (Septi-Chek, BD Diagnostic Systems, Sparks, MD) may be preferred. Several automated, continuously monitored blood culture systems are available for higher volume laboratories. These include the ESP (Trek Diagnostics, Inc., Cleveland, Ohio), BacT/Alert (bio Mérieux, Durham, NC), and BACTEC (BD Diagnostic Systems, Sparks, MD) systems (9–15). Always follow the manufacturer’s recommendations for the specific system, using the maximum amount of blood samples recommended. The ratio of blood to broth is the most critical factor in fungal recovery, and should be near 1:5 in most systems (16). Lysis centrifugation methods, either commercially available as the Isolator™ system (Wampole Labora- tories, Princeton, NJ) or manual methods (17,18), are recommended for dimorphic fungal pathogens and filamentous fungi (19,20). Intravascular catheter tips are also frequently submitted, and should be cultured according to the semiquantitative method of Maki (8). Blood cultures should also be drawn at the time of catheter removal to correlate catheter colony counts and organisms recovered with catheter-related septicemia. Catheter colony counts of less than 15 are less likely to forewarn of septicemia. Specimens should be transported, at room temperature, to the laboratory as soon as possible, ideally within 2 hours. Exceptions include storage of central nervous system specimens at 30ºC, and 4ºC extended storage for specimens likely to have bacterial contamination. Hair, skin, and 2. Basic Mycology 17 nails may be transported in clean paper envelopes. Several sources provide specific guide- lines for the collection, transport, and processing of various types of specimens for fungal culture (8,21,22). See Table 2.1 for common collection sites. Table 2.1 Common specimen collection sites for fungal culturesa Collection site Comments Abscesses, subcutaneous sites Aspirate abscess; sample base of subcutaneous lesions Blood Use maximum amount of blood recommended for the system being used Bone marrow Pediatric Isolator™ recommendedb CSF Do not refrigerate Draining sinus tracts Search for granules of eumycotic mycetoma; wash several times with saline containing antibiotics Ear Rotate swab firmly in outer ear Eye Inoculate corneal scrapings directly only plates in a “C” shape Hair Use forceps to collect several hairs with shaft intact and sample any active lesions Intravenous catheters Use Maki method Lower respiratory Process promptly for dimorphic pathogens (BAL, brush, aspirate, wash, sputum) Medical devices (valves, hardware, etc.) Dislodge any biofilms before inoculation into liquid medium Nails For dermatophytes, agents of dermatomycoses, and Candida spp.; clean with 70% alcohol; collect subungual debris and clip affected nails Nasal sinus Surgical collection, commonly ethmoid and maxillary sinuses Open wound Aspirate or swab vigorously Prostatic fluid Primarily for blastomycosis Skin For dermatophytes; clean with 70% alcohol and scrape vigorously Sterile body fluids May be concentrated by centrifugation or syringe filtration Tissue Surgical collection; use punch biopsies for skin lesions Urine Early morning midstream collection Vagina Primarily for refractory vaginal candidiasis Vitreous fluid Needle aspiration Upper respiratory (oral) Swab lesions, use selective media for yeasts aThis list is not all inclusive. bWampole Laboratories, Princeton, NJ. 18 Deanna A. Sutton Before receipt in the mycology laboratory, a portion of all tissue samples submitted for culture should also be placed in formalin for submission to the histology laboratory. Histopathologic examination with appropriate stains is usually necessary to document fungal invasion. These may include the routine hematoxylin and eosin stain (H&E), Gomori methenamine silver stain (GMS), periodic acid-Schiff stain (PAS), and others. A discussion of the use of histopathology and of mycological stains is provided in Chapter 3 of this book. As part of routine processing, the mycology laboratory should also examine a portion of the specimen directly via microscopy, typically with the use of a potassium hydroxide (KOH) preparation, Gram stain, calcofluor white fluorescent stain, India ink stain (limited to cerebrospinal fluid examination for Cryptococcus neoformans), or some other method (Table 2.2). Observation of fungal structures via direct microscopy and/or histopathology is essential to corroborate organism recovery in culture (rule out contamination). The media used for primary isolation may vary according to personal preference; however, certain basic tenets apply to all media used for primary recovery. Material from nonsterile sites should be cultured on media that will support fungal growth but also inhibit bacteria. Antibacterial agents, alone or in combination, are added for this purpose. Common choices include chloramphenicol (<16 μg/ml), gentamicin (5 to 100 μg/ml), penicillin (20 U/ml), streptomycin (40 μg/ml), and ciprofloxacin (5 μg/ml). These agents should not be included, however, when actinomycetes are suspected. Media may also be made selective by the addition of the eukaryotic protein synthesis inhibitor cyclo- heximide at 0.5 μg/ml. This may be useful in the detection of dimorphic fungi and dermatophytes; however, many clinically significant, saprobic fungi may be suppressed, leading to failure in recovering opportunistic etiologic agents in compromised hosts. Therefore, media with and without this agent should routinely be employed. Enriched Table 2.2 Useful direct microscopy methods for the routine mycology laboratorya Method Comments Calcofluor white Requires fluorescence microscope; can be used with KOH to detect all fungi, including Pneumocystis Gram stain Detects most fungi present, however Cryptococcus spp. may exhibit only faint staining Giemsa stain Several modifications; detects intracellular Histoplasma capsulatum and intracystic bodies and trophozoites of Pneumocystis India Ink stain Commonly used from demonstration of capsular material of Cryptococcus neoformans in CSF Potassium hydroxide Clears debris so fungi more readily observed; stains may be added for better visualization of fungal elements Wright stain Useful to detect intracellular Histoplasma capsulatum in bone marrow and peripheral smears aAdditional fungal stains are available through the histopathology laboratory. This list is not all inclusive. 2. Basic Mycology 19 media with 5% to 10% sheep erythrocytes may be incorporated into the battery for fastidious thermally dimorphic fungi such as Histoplasma capsulatum and Blastomyces dermatitidis. Peptone-based versus plant-based media may also be a consideration. Many of the opportunistic filamentous fungi prefer plant-based media, producing more typical colony morphologies and more diagnostic structures, thus increasing the potential to make identification possible from primary plates. Plant-based media may also be made selective with antibacterial agents or cycloheximide. Table 2.3 lists several commercially available media that may be used for both primary isolation and identification. The choice of tubed versus plated media is made based on space constraints, personal preference, and safety. The greater surface area provided by plates is preferred by many laboratorians (and always preferred by the fungi!), as manipulation of cultures, isolation procedures, and so forth is more easily performed on plates. When used, plate lids should be firmly attached with an air-permeablematerialorplatessealed inair-permeablebags toavoidcross-contamination or laboratory worker exposure. Optimally, cultures should be incubated at 30ºC (± 1ºC). If this temperature is not available, room temperature near 25ºC should be used. A 7-day incubation is generally adequate when screening for yeasts from oropharyngeal or vaginal sites. Although Table 2.3 Media useful for primary isolation and identificationa Medium Uses/comments Sabouraud dextrose agar (SDA) For yeasts Usually adequate for aspergilli Poor color and conidiation for black moulds Classic morphologic descriptions for dermatophytes CHROMagar Candidab Contains chromogenic substrates and antimicrobial agents; for isolation and identification of yeasts Albicans IDc As above Potato dextrose agar (PDA) Useful for all mould recovery/identification Potato flakes agar (PFA) Brain heart infusion agar (BHI) Inhibitory mould agar (IMA) Yeast extract phosphate medium Sabhi agar Mycosel agar™d or Mycobiotic agar SDA with chloramphenicol and cycloheximide Dermatophyte test medium (DTM) Dermatophyte identification medium (DIM) aThis list is not all-inclusive. All are commercially available. bCHROMagar Microbiology, Paris, France. cbioMérieux, Marcy l’Etoile, France. dBD Diagnostic Systems, Sparks, MD. 20 Deanna A. Sutton 4-week incubation times have traditionally recommended, recent studies suggest that 3 weeks is adequate to detect growth of a fungi from most other specimens, excluding those from skin, hair, and nails, and in cultures requested specifically to attempt to recover dimorphic pathogens (23). The time required for development of diagnostic structures, particularly for some coelomycetes and ascomycetes, may be considerably longer, up to several weeks (24). 3. EXAMINING CULTURES Cultures should be examined every day for the first 3 days and preferably twice a week thereafter. Cultures of yeasts are typically creamy to waxy, while moulds appear velvety to woolly to cottony. Some safety precautions common to both yeasts and moulds include the careful handling of plates and tubes so as not to create aerosols of infectious material and the prevention of contamination of patient cultures with ubiquitous fungi from the work surroundings. 3.1. Yeast and Yeast-like Organism Identification One may handle yeast cultures, consisting of unicellular organisms that replicate by budding, on the open bench, adhering to the same safety precautions as for bacteria. Yeast and yeast-like fungi should be examined for their colony color (white to cream to pink; brownish-black for the yeast synanamorph of Exophiala species when observed on Sabouraud dextrose agar; blue to green to pink for Candida species on CHROMagar Candida™ [CHROMagar Microbiology, Paris, France]), growth rate, temperature requirements (or preferences), macroscopic morphology (smooth, wrinkled, glabrous, moist, dry, etc.), and microscopic morphology (size and shape, presence of blasto- conidia, capsules, germ tubes, pseudohyphae, true hyphae, chlamydoconidia, etc.). Yeast morphology is most reliably observed on a cornmeal agar plate via the Dalmau method (25). This technique involves streaking a very small amount of yeast onto a plate in two parallel lines, streaking back and forth over these lines for better isolation, and covering the area with a flame-sterilized coverslip. The plate is incubated at room temperature for 18 to 24 hours and then examined microscopically for diagnostic struc- tures. Tease mounts may also provide useful information. Additional procedures that may be required for identification of yeast include the reduction of nitrate to nitrite, urease activity, the ability of the organism to grow on media containing cycloheximide, and assimilation and fermentation patterns. Many commercial systems, both manual and automated, are available to assist in yeast identification. 3.2. mould Identification Any filamentous organisms recovered on culture should be examined and manip- ulated in a biological safety cabinet. While moulds can be recovered on a variety of media, conidiation/sporulation is generally enhanced on plant-based media. If not used in primary isolation, plant-based media should be employed in identification schema. moulds should be examined for their growth rate, temperature requirements, and macro- scopic morphology to include color (hyaline to brightly colored or phaeoid [brownish to blackish]), texture (velvety, woolly, granular, cottony, etc.), and the observation of any diagnostic features visible to the naked eye. The microscopic detail may be studied 2. Basic Mycology 21 using tease mounts or temporary tape mounts (clear tape only) in lactophenol cotton blue. The preferred technique to demonstrate diagnostic structures and methods of conidiogenesis for most filamentous fungi is the slide culture method. This method also provides a permanent mount that can be preserved in a slide collection for future studies and is extremely useful for comparison with other similar isolates or atypical strains. Slide cultures should not, however, be set up on moulds in which the clinical history suggests a dimorphic pathogen such as Histoplasma capsulatum, Blastomyces dermati- tidis, Coccidioides species, Paracoccidioides brasiliensis (not commonly seen in the United States), or Penicillium marneffei (usually restricted to human immunodeficiency virus [HIV]-infected individuals from endemic areas of Southeast Asia). Tease mounts should be prepared for these isolates in a mounting fluid known to kill the fungus, such as lactophenol cotton blue. Sporothrix schenckii, another dimorphic organism, poses less of an exposure risk, and may be examined via slide culture. Histoplasma capsulatum, B. dermatitidis, and Coccidioides species may be definitively identified using DNA GenProbe® (AccuProbe, San Diego, CA) methodology. Zygomycetes may rapidly overgrow slide cultures, making the method less than optimal for studying this group of fungi. 4. TAXONOMY, CLASSIFICATION, AND NOMENCLATURE Many volumes have been dedicated to the taxonomy, classification, and nomen- clature of clinically significant fungi. Herein, this work highlights only some of the basic concepts. The classification scheme accepted by most authorities is presented for the kingdom Fungi. The term classification, in the fungal sense, refers to the application of names for the categories into which the taxa (taxonomic groups) may be grouped, with some subdivisions regarding their relative order. “Taxonomy” refers to

this classification in a very systematic way, and nomenclature is the assigning of names to fungi that must abide by the rules of the International Code of Botanical Nomenclature (ICBN). The following is an abbreviated classification scheme for the kingdom Fungi: Group Group Ending Kingdom none Phylum -mycota Class -mycetes Order -ales Family -aceae Genus -no specific ending Species -no specific ending Variety -no specific ending The phyla in which the sexual or teleomorph forms of the majority of human/animal pathogens reside are the Ascomycota, Basidiomycota, and Zygomycota (1). An example of this classification scheme for the ascomycete Microascus cinereus, an etiologic agent of nail infections, maxillary sinusitis, endocarditis, and brain abscess would look like this: 22 Deanna A. Sutton Kingdom: Fungi Phylum: Ascomycota Order: Microascales Family: Microascaceae Genus: Microascus Species: Microascus cinereus Microascus cinereus, a sexual fungus (or the teleomorph) that produces perithecia, asci, and ascospores in culture, also simultaneously produces an asexual form (the anamorph) that is microscopically quite different. Asexual fungi, previously given the prefix “Form-” in the classification scheme, such as Form-Class, Form-Order, etc., are now commonly known as “mitosporic” fungi, or those reproducing my mitosis rather than meiosis. The anamorphic form of Microascus cinereus is the phaeoid fungus Scopulariopsis cinereus. Anamorphic fungi are identified mostly on the basis of their method of conidiogenesis (how they form their reproductive structures). Asexual repro- ductive propagules are referred to as conidia, hence the term conidiogenesis. Sexual fungi are identified mostly based on the method they use to form their sexual repro- ductive propagules (ascospores, basidiospores, or zygospores). Not all taxonomists agree that we should apply different names to the anamorph and teleomorph of the same fungus, the holomorph, or “whole fungus”; however, this is the current practice. Adding to this confusion, some fungi produce multiple anamorph forms, such as is seen with the fungus Pseudallescheria boydii. Pseudallescheria boydii is the teleo- morph, Scedosporium apiospermum is the anamorph, and Graphium eumorphum is the synanamorph, or other anamorphic form of the “whole fungus.” Practically speaking, most etiologic agents are identified in the laboratory on the basis of structures formed by the anamorphic form of the fungus. Although many mitosporic fungi have known teleomorphs, most require two mating strains to produce the sexual form. These are referred to as heterothallic. A few clinically significant fungi require only one strain to produce the teleomorph, and these are considered homothallic. Microascus cinereus and Pseudallescheria boydii, cited in the preceding text, are examples of homothallic fungi. 5. FUNGAL IDENTIFICATION Yeast identification is performed in a manner similar to that for bacterial identifi- cation, and easily lends itself to various compartmentalized and automated methods that measure various physiologic characteristics. Mould identification, however, currently relies more on the observation of macroscopic morphologies, such as color and colonial features, growth rate, temperature maximums and minimums, and microscopic struc- tures. Some of these more common identifying characteristics are exemplified in the organisms chosen in the thumbnail sketch of the kingdom Fungi as illustrated in Table 2.4. 5.1. Ascomycota Under the phylum Ascomycota, the ascomycetous yeasts are usually identified by yeast methods, while the moulds are identified based on the structures they produce. Some of the filamentous homothallic ascomycetes produce ascomata known as cleistothecia, perithecia,orgymnothecia inwhich theasciandascosporesarecontained(Figs.2.1 to2.4). 2. Basic Mycology 23 Table 2.4 Simplified schematic of the kingdom Fungi for most human/animal pathogens Phylum Ascomycota Class Hemiascomycetes—yeasts Class Euascomycetes—moulds; produce ascospores in a variety of sexual structures known as ascomata (pl.), ascoma (sing.) Cleistothecium—round, closed ascoma Example: Pseudallescheria boydii, Fig. 2.1 Perithecium—pear-shaped ascoma, with an opening or ostiole Example: Microascus cirrosus, Fig. 2.2 Gymnothecium—ascoma with a loose network of hyphae Example: Myxotrichum deflexum, Fig. 2.3 Asci (pl.), ascus (sing.)—within the ascoma and containing ascospores Ascospores, various sizes, shapes, colors, ornamentation Example: Sporomiella sp., Fig. 2.4 Phylum Basidiomycota Class Urediniomycetes—contains a few red yeasts Class Ustilaginomycetes—contains yeast-like members of smut fungi Class Hymenomycetes—contains mushrooms (basidiocarps) producing yeast anamorphs (Cryptococcus species) and filamentous anamorphs that are frequently sterile or may produce arthroconidia Example: Schizophyllum commune, a human etiologic agent, produces spicules (small protrusions) along the hyphae, Fig. 2.5 Basidiospores sometimes seen from basidiocarps of S. commune, Fig. 2.6 Phylum Zygomycota Class Zygomycetes Order Mucorales—asexual reproduction by multispored or few- (to one) spored sporangia (sporangiola) Heterothallic genera (require two mating strains) include some spp. of Rhizopus, Absidia, Mucor, and others; produce sporangiospores Example: Rhizopus microsporus var rhizopodiformis, Fig. 2.7 Homothallic genera/species (one mating strain required) produce zygospores Example: Cokeromyces recurvatus, Fig. 2.8 Order Entomophthorales—characterized by forcibly discharged conidia. Produce asexual primary conidia and smaller secondary conidia Example: Conidiobolus incongruus, Fig. 2.9 Example: Basidiobolus ranarum, produces zygospores Mitosporic Fungi (formerly Fungi Imperfecti) Methods of conidiogenesis Blasticconidia blown out Phialidic conidiogenous cell—often have discernible collarettes and produce phialoconidia Example: Phialophora americana, Fig. 2.10, and Aspergillus flavus, Fig. 2.11 Annellidic conidiogenous cells—have rings or annellations and become longer and narrower with production of annelloconidia Example: Scopulariopsis cirrosus, Fig. 2.12 (Continued) 24 Deanna A. Sutton Table 2.4 (Continued) Some species blow out conidia through pores on geniculate conidiophores Example: Bipolaris hawaiiensis, Fig. 2.13 Thallic—conidia formed from preexisting hypha Arthroconidia produced that may or may not have intervening disjunctor cells Example: Coccidioides species, Fig. 2.14, and dematiaceous arthroconidia of Scytalidium dimidiatum, Fig. 2.15 Hyphomycetes—bear their conidia free and display various colors, methods of conidiogenesis, growth rates, etc. Example: Aspergillus flavus, Fig. 2.11 Coelomycetes—bear their conidia within some type of asexual structure known as a conidioma (sing.) [ conidiomata (pl.)] and display various colors, methods of conidiogenesis„ growth rates, etc. Pycnidium—round conidioma with an opening (ostiole) and contained within; Example: Phoma species, Fig. 2.16 Acervulus—flat, cup-shaped conidioma, with conidia more or less exposed Example: Colletotrichum species Fig. 2.1. Globose ascoma (closed cleistothecium) of Pseudallescheria boydii. [Figure in color on CD-ROM]. 2. Basic Mycology 25 Fig. 2.2. Pear-shaped ascoma (perithecium with an opening or ostiole) of Microascus cirrosus. [Figure in color on CD-ROM]. 5.2. Basidiomycota Similarly, the red and white yeasts within the phylum Basidiomycota are commonly identified via yeast methodologies. The filamentous basidiomycetes pose identification dilemmas, as they frequently remain sterile in culture, producing no unique reproductive structures. Schizophyllum commune is one of the few that may sometimes be tentatively identified by its production of spicules along the sides of the hyphae, and occasionally by clamp connections (Fig. 2.5), basidiocarps, and basidiospores (Fig. 2.6) when dikaryons (compartments of a hypha that contain two nuclei, each derived from a different parent) are present. 5.3. Zygomycota Human and animal pathogens of the phylum Zygomycota are contained within two orders in the class Zygomycetes; the Mucorales and the Entomophthorales. The Mucorales contain the most common zygomycete genera such as Absidia, Rhizopus (Fig. 2.7), Mucor, Rhizomucor, Cunninghamella, and Cokeromyces (Fig. 2.8), while the 26 Deanna A. Sutton Fig. 2.3. Gymnothecium (ascoma with a loose hyphal network surrounding central ascospores) of Myxotrichum deflexum. [Figure in color on CD-ROM]. Fig. 2.4. Asci containing dark ascospores of a Sporomiella species. [Figure in color on CD-ROM]. 2. Basic Mycology 27 Fig. 2.5. Spicules and clamp connections on hyphae of Schizophyllum commune. [Figure in color on CD-ROM]. Fig. 2.6. Basidiospores produce by Schizophyllum commune. [Figure in color on CD-ROM]. 28 Deanna A. Sutton Fig. 2.7. Ramified rhizoids, short, dark sporangiophores, collapsed columellae, and sporan- giospores of Rhizopus microsporus var. rhizopodiformis. [Figure in color on CD-ROM]. Fig. 2.8. Central vesicle, recurving stalks with terminal sporangioles containing sporan- giospores, and thick-walled zygospores of Cokeromyces recurvatus. [Figure in color on CD- ROM]. 2. Basic Mycology 29 Entomophthorales encompass the less frequently seen genera Conidiobolus (Fig. 2.9) and Basidiobolus (both characterized by forcibly discharged conidia). 5.4. Mitosporic Fungi The group that contains the most human etiologic agents, by far, is one known as the “Mitosporic Fungi,” or previously, the “Fungi Imperfecti.” While these fungi may by related to various sexual phyla, these associations have not been yet demonstrated, and therefore these fungi are identified on the basis of their asexual rather than sexual repro- ductive propagules (method of conidial formation or conidiogenesis). Two main groups exist within the mitosporic fungi. The hyphomycetes bear their conidia free to the air, whereas the conidia of the coelomycetes are contained within some type of enclosed to semi-enclosed structure. The hyphomycetes contain numerous common moniliaceous (hyaline) and phaeoid or dematiaceous (dark) genera and generally produce their conidia by either blastic or thallic methods. Blastic conidia are “blown out” of some type of conid- iogenous cell. These include those produced from phialides, as in Phialophora species (Fig. 2.10) or Aspergillus species such as A. flavus (Fig. 2.11), or from annellides, as in Scopulariopsis cirrosus (Fig. 2.12). Some species blow out their conidia through pores, such as in Bipolaris hawaiiensis (Fig. 2.13). Thallic conidia are formed from preexisting hyphae, as in Coccidioides species (Fig. 2.14), Malbranchea species, and Scytalidium Fig. 2.9. Primary sporangiole giving rise to secondary sporangiole of Conidiobolus coronatus. [Figure in color on CD-ROM]. 30 Deanna A. Sutton Fig. 2.10. Phialides of Phialophora americana with deep collarettes producing phialo- conidia. [Figure in color on CD-ROM]. Fig. 2.11. Rough conidiophore and biseriate fruiting head of Aspergillus flavus. [Figure in color on CD-ROM]. 2. Basic Mycology 31 Fig. 2.12. Annellides and chains of annelloconidia produced by Scopulariopsis cirrosus. [Figure in color on CD-ROM]. Fig. 2.13. Geniculate conidiophores with pores through which the conidia of Bipolaris hawaiiensis are blown out. [Figure in color on CD-ROM]. 32 Deanna A. Sutton Fig. 2.14. Hyphae and arthroconidia with disjunctor cells of Coccidioides species. [Figure in color on CD-ROM]. Fig. 2.15. Dematiaceous hyphae and arthroconidia of Scytalidium dimidiatum which lack disjunctor cells. [Figure in color on CD-ROM]. dimidiatum (Fig. 2.15). The structures produced by coelomycetes to contain their conidia are known as conidioma (sing.) or conidiomata (pl.). They may be round structures with an opening or ostiole known as a pycnidium, as in Phoma species (Fig. 2.16), or a flat, cup-shaped, semi-enclosed structure known as an acervulus. The conidiogenous cells within both of these conidiomata may be either phialidic or annellidic. 2. Basic Mycology 33 Fig. 2.16. Conidioma of a Phoma species containing a large central ostiole or opening. [Figure in color on CD-ROM]. REFERENCES 1. Howard DH. An introduction to the taxonomy of zoopathogenic fungi. In: Howard DH, ed. Pathogenic fungi in humans and animals. 2nd ed. Vol 16. New York: Marcel Dekker, 2003:1–16. 2. Sutton DA, Fothergill AW, Rinaldi MG. Guide to clinically significant fungi. Baltimore: Lippincott Williams & Wilkins, 1998. 3. Bartlett JG, Ryan KJ, Smith TF, Wilson WR. Cumitech 7A, Laboratory diagnosis of lower respiratory tract infections. Washington II JA, Coordinating ed. Washington, DC: American Society of Microbiology, 1987. 4. Clarridge Je, Pezzlo MT, Vosti KL. Cumitech 2A. Laboratory diagnosis of urinary tract infections. Weissfeld AW, coordinating ed. Washington, DC: American Society for Micro- biology, 1987. 5. Eschenbach D, Pollock HM, Schacter J. Cumitech 17. Laboratory diagnosis of female genital tracts infections. Rubin SJ, coordinating ed. Washington, DC: American Society for Microbiology, 1983. 6. Jones DB, Liesegang TJ, Robinson NM. Cumitech 13. Laboratory diagnosis of ocular infections. Washington JA, coordinating ed. Washington, DC: American Society for Micro- biology, 1981. 34 Deanna A. Sutton 7. Maki DG, Weise CD, Sarafin HW. A semiquantitative culture method for identifying intravenous-catheter-related infection. N Engl J Med 1977;296:1303–1309. 8. Sutton DA. Specimen collection, transport, and processing: mycology. In: Murray PR, Baron EJ, Jorgensen JH, Landry ML, MA Pfaller MA, eds. Manual of clinical microbiology. 9th ed. Washington, DC: American Society for Microbiology, 2007;1728–1736. 9. Jorgensen JH, Mirrett S, McDonald LC, et al. Controlled clinical laboratory comparison of BACTEC Plus Aerobic/F resin medium with BacT/Alert aerobic FAM medium for detection of bacteremia and fungemia. J Clin Microbiol 1997;35:53–58. 10. Mattia AR. FDA review criteria for blood culture systems. Clin Microbiol Newsl 1993;15:132–136. 11. Horvath LL, George BJ, Murray CK, Harrison LS, Hospenthal DR. Direct comparison of the BACTEC 9240 and BacT/ALERT 3D automated blood culture systems for Candida growth detection. J Clin Microbiol 2004;42:115–118. 12. Horvath LL, Hospenthal DR, Murray CK, Dooley DP. Detection of simulated candidemia by the BACTEC 9240 SYSTEM WITH plus Aerobic/F and Anaerobic/F blood culture bottles. J Clin Microbiol 2003;41:4714–4717. 13. Horvath LL, Hospenthal DR, Murray CK, Dooley DP. Direct isolation of Candida spp. from blood cultures on the chromogenic medium CHROMagar Candida. J Clin Microbiol 2003;41:2629–2632. 14. McDonald LC, Weinstein MP, Fune J, Mirrett S, Reimer LG, Reller LB. Controlled comparison of BacT/ALERT FAN aerobic medium

and BACTEC fungal blood culture medium for detection of fungemia. J Clin Microbiol 2004;39:622–624. 15. Meyer M-H, Letscher-Bru V, Jaulhac B, Waller J, Candolfi E. Comparison of Mycosis IC/F and Plus Aerobic/F Media for diagnosis of fungemia by the BACTEC 9240 system. J Clin Microbiol 2004;42:773–777. 16. Auckenthaler R, Ilstrup DM, Washington II JA. Comparison of recovery of organisms from blood cultures diluted 10% (volume/volume) and 20% (volume/volume). J Clin Microbiol 1982;15:860–864. 17. Billi J, Stockman L, Roberts GD, Horstmeier CD, Istrup DM. Evaluation of a lysis- centrifugation system for recovery of yeasts and filamentous fungi from blood. J Clin Microbiol 1983;18:469–471. 18. Bille J, Edson RS, Roberts GD. Clinical evaluation of the lysis-centrifugation blood culture system for detection of fungemia and comparison with a conventional biphasic broth blood culture system. J Clin Microbiol 1984;19:126–128. 19. Guerra-Romero L, Edson RC, Dockerill FR, Horstmeier CD, Roberts GD. Comparison of Dupont Isolator and Roche Septi-check for detection of fungemia. J Clin Microbial 1987;25:1623–1625. 20. Lyon R, Woods G. Comparison of the BacT/Alert and ISOLATOR blood culture systems for recovery of fungi. Am J Clin Pathol 1995;103:660–662. 21. Hazen KC. Section 6. Mycology and aerobic actinomycetes. In: Isenberg HD, ed. Essential procedures for clinical microbiology. Washington, DC: American Society for Microbiology, 1998:255–283. 22. Miller JM. A guide to specimen management in clinical microbiology. 2nd ed. Washington, DC: American Society for Microbiology Press, 1999. 23. Labarca JAI, Wagar EA, Grasmick AE, Kokkinos HM, Bruckner DA. Critical evaluation of a 4-week incubation for fungal cultures: is the fourth week useful? J Clin Microbiol 1998; 36:3686–3685. 24. Sutton DA. Coelomycetous fungi in human disease. A review: clinical entities, pathogenesis, identification and therapy. Rev Iberoam Micol 1999;16:171–179. 25. McGinnis MR. Laboratory handbook of medical mycology. New York: Academic Press, 1980. 2. Basic Mycology 35 SUGGESTED READINGS Chandler FW, Watts JC. Pathologic diagnosis of fungal infections. Chicago: American Society of Clinical Pathologists Press, 1987. deHoog GS, Guarro J, Gene J, Figueras MJ. Atlas of clinical fungi. 2nd ed. Utrecht, The Netherlands: Centraalbureau voor Schimmelcultures, 2000. Larone DH. Medically important fungi: a guide to identification. 4th ed. Washington, DC: American Society for Microbiology Press, 2002. Mandell GL, ed. in Chief, Diamond RD, ed. Atlas of infectious diseases. Fungal infections. Philadelphia: Current Medicine, 2000. Miller JM. A guide to specimen management in clinical microbiology. 2nd ed. Washington, DC: American Society for Microbiology Press, 1999. Sutton DA. Specimen collection, transport, and processing: mycology. In: Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA, eds. Manual of clinical microbiology. 9th Ed. Washington, DC: American Society for Microbiology, 2007;1728–1736. Sutton DA, Fothergill AW, Rinaldi MG. Guide to clinically significant fungi. Baltimore: Lippincott Williams & Wilkins, 1998. www.doctorfungus.org is an excellent source for current names and morphology of fungi of medical importance. 3 Diagnostic Histopathology Michael B. Smith, MD and Michael R. McGinnis, PhD 1. INTRODUCTION Fungal infections can be diagnosed on the basis of mycologic, immunologic, clinical, and histopathologic information. Of these procedures, histopathology can provide important diagnostic information in a relatively short period of time, but is limited in that much of the information obtained from the examination of tissue sections can provide only tentative fungal identification, unless specialized techniques such as immunofluorescence are used or when the etiologic agent has distinctly unique structures (such as spherules containing endospores). These limitations are particularly evident in the case of filamentous fungi, as many of the opportunistic filamentous pathogens have similar tissue morphology (Fig. 3.1). Although this often makes identi- fication of these organisms from tissue sections essentially impossible, examination of tissue sections is critical in determining whether fungi are involved in invasion, colonization, or simply have been recovered in culture as contaminants. The technique is rapid, inexpensive, and accurate, and the information it provides can have enormous and immediate patient care implications. Even though the most specific method in identifying a fungus is to recover it in culture so that it can be properly and accurately identified, cultures may not be submitted for various reasons. In addition, some organisms, such as Lacazia loboi (Fig. 3.2) and Rhinosporidium seeberi (Fig. 3.3), have not yet been grown in vitro. In the absence of culture recovery, the diagnosis of fungal infection via histology rests on the size, morphology, and staining properties of fungal elements in tissue along with the assessment of invasion of normally sterile tissue and body fluids. 2. STAINS A number of specific stains are available that can assist in visualizing fungi in tissue (Table 3.1). With the exception of immunofluorescence using species-specific antibodies, all stains are nonspecific and serve only to demonstrate the morphological structures of the fungus, which usually allows categorization in most cases, or definitive identification to species in some cases. A good example is the ability of mucicarmine to stain the polysaccharide capsule of Cryptococcus neoformans (Fig. 3.4). Although not completely specific, with the appropriate morphology of the yeast cells, the staining From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 37 38 Michael B. Smith and Michael R. McGinnis Fig. 3.1. Septate, uniform hyphae of Aspergillus fumigatus. Hyphae morphology is charac- teristic but not specific. GMS. [See color plate 1, following p. 48]. [Figure in color on CD-ROM]. Fig. 3.2. Uniform, yeast-like cells in chains of Lacazia loboi. GMS. (Photo courtesy of Dr. A. Padhye). [See color plate 2, following p. 48]. [Figure in color on CD-ROM]. 3. Diagnostic Histopathology 39 Fig. 3.3. Large sporangium containing sporangiospores and smaller trophocytes of Rhinosporidium seeberi. PAS. [See color plate 3, following p. 48]. [Figure in color on CD-ROM]. Table 3.1 Stains useful in the diagnosis of fungal infection Stain Reaction Comments Fontana-Masson Chromaffin reaction that oxidizes Useful for staining cell walls of melanin or melanin precursor suspected dematiaceous as it reduces silver. Fungal cell fungi when the nature walls are black. Background is of their cell wall is not pale pink. evident. Useful for staining Cryptococcus neoformans. Natural color of cell walls masked by this staining technique. Tissue response cannot be studied. Gomori methenamine Chromic acid oxidizes cell wall Enhances visualization of fungi silver (Grocott’s polysaccharides to aldehydes. and their morphology. Natural modification) (GMS) Aldehyde products reduce color of cell walls masked by methenamine silver nitrate to the staining. Tissue response metallic silver. Erythrocytes cannot be studied. Ideal and fungal cell walls are special fungal stain to brown-to-black. Background is evaluate fungal structures. pale green. Cell nuclei can mimic yeasts. (Continued) 40 Michael B. Smith and Michael R. McGinnis Table 3.1 Continued Stain Reaction Comments Gridley’s Fungus Chromic acid oxidizes adjacent Enhances visualization of fungi hydroxyl groups of cell wall and their morphology. Natural polysaccharides to aldehydes. color of cell walls masked. Aldehyde groups combine Tissue response cannot be with Schiff reagent. Aldehyde studied. fuchsin occupies uninvolved linkages of the Schiff reagent. Fungal cell walls are rose to purple and the background is yellow. Hematoxylin and Hematein-mordant stains DNA Visualizes host tissue response eosin (H&E) in the nucleus and nuclear to the fungus. Aspergillus and proteins. Nuclei blue, zygomycetes stain well. cartilage and calcium Difficult to see some fungi in deposits blue; cytoplasm and tissue, especially if they are other components shades of present in small numbers. red and erythrocytes bright Dematiaceous nature of fungal red. cell wall can often be seen. Immunofluorescence Direct technique: Specific Specific and highly fluorescein-labeled antibody sensitive. Some use reacts with fungal cell wall immunoperoxidase technique. antigens. Can be used to detect and Indirect technique: Unlabeled measure antibodies. Reagents antibody complexes with often available only in fungal antigens. specialized laboratories. Fluorescein-labeled conjugate reacts with globulins attached to fungal antigens. Cell walls fluoresce yellow-green. Mayer’s Mucicarmine Aluminum binds acid groups of Alcian blue may also be used as the mucopolysaccharides of capsular stain. Not specific for the capsule where carmine is Cryptococcus neoformans. attached as a complex. Rhinosporidium seeberi Capsule stains deep rose to and Blastomyces dermatitidis red. Background is yellow. cells are occasionally stained. Periodic acid-Schiff Periodic acid oxidizes adjacent Enhances visualization of fungi (Hotchkiss-McManus hydroxyl groups of cell wall and their morphology. Natural technique) (PAS) polysaccharides to aldehydes. color of cell walls is masked. Aldehyde combines with Tissue response cannot be Schiff reagent. Fungi are studied. red-purple. Background is green. 3. Diagnostic Histopathology 41 Fig. 3.4. Mucicarmine stain demonstrating positive staining of capsule of Cryptococcus neoformans. Mayer’s mucicarmine. [See color plate 4, following p. 48]. [Figure in color on CD- ROM]. allows a presumptive diagnosis of C. neoformans. The ability of these fungal stains to highlight the appearance of the organisms does, however, come with some disadvan- tages, as the stains mask the presence of pigment in the walls of the pigmented fungi (Fig. 3.5), and neither the host inflammatory reaction nor the viability of the tissue in Fig. 3.5. Pigmented brown sclerotic bodies seen in a case of chromoblastomycosis. The pigment would be masked in a GMS stain. H&E. [See color plate 5, following p. 48]. [Figure in color on CD-ROM]. 42 Michael B. Smith and Michael R. McGinnis which the fungus is present can be assessed. The latter may be crucial in determining whether the fungus is invasive. The routine hematoxylin and eosin (H&E) stain is extremely valuable for studying the host’s response to the fungus. Frequently, fungi are difficult to see in H&E stained tissue sections because they are not readily stained by this technique. The aspergilli and zygomycetes tend to be an exception because they usually stain very well. In addition to difficulties in recognizing fungi in tissue, especially when their numbers within the pathologic process are small, their presence can be overlooked. Because stains such as the Gomori methenamine silver (GMS), Gridley fungus, and periodic acid-Schiff (PAS) stain the fungus, they provide the advantage of allowing the histopathologist to clearly see small numbers of fungi as well as their morphology. A number of histopathologists find a combined H&E and GMS stain to be an excellent technique because it clearly distinguishes the fungus and at the same time allows visualization of the tissue reaction. 3. FUNGAL MORPHOLOGY Confusion may result from tissue components associated with pathologic processes that resemble fungi. These include Russell bodies, karyorrhectic debris, calcified bodies, elastic fibers, small blood vessels, and other host components. Care must always be exercised when examining tissue. Multiple fields should always be examined microscopically before reaching a diagnosis. When determining whether a structure represents a fungus, and if so, which species it represents, the morphology of structures in tissue must always be carefully evaluated. 3.1. Yeasts in Tissue Yeast cells are characterized by their size, budding (location and attachment of daughter cells), color (hyaline or dematiaceous), presence or absence of a capsule, number of nuclei, and thickness of their cell walls. Other associated forms, such as pseudohyphae (well developed or rudimentary), hyphae, and arthroconidia, are helpful in identifying the etiologic agents. Dimorphic fungi, yeasts such as Candida albicans, and several other fungi may produce yeast cells in tissue. The location of yeast cells can provide valuable data. For example, H. capsulatum forms solitary, budding 2 to 5 μm cells that are intracellular (Fig. 3.6). Care must be taken to avoid confusing H. capsu- latum with Penicillium marneffei, another intracellular dimorphic fungus (Fig. 3.7). The yeast cells of P. marneffei divide by fission, and not by budding as in H. capsulatum. Geographically, infection with P. marneffei is limited to Southeast Asia. 3.2. Hyphae in Tissue Hyphae are filaments that are characterized by their diameter, branching pattern, septation, color, consistency of shape, cell wall contour, and organizational pattern. A sclerotium (syn. grain, granule) is a macroscopic structure with a distinct, organized, hyphal architecture, whereas a fungus ball consists of a mass of disorganized hyphae. The fungus ball overall can be organized as repeating zones of hyphae and necrotic tissue. Additional structures such as arthroconidia, blastoconidia, vesicles, chlamydo- 3. Diagnostic Histopathology 43 Fig. 3.6. Small intracellular yeast with budding, characteristic of Histoplasma capsulatum. GMS. [See color plate 6, following p. 48]. [Figure in color on CD-ROM]. conidia, and others are helpful for the recognition of different fungi and fungus-like pathogens. 3.3. Other Structures in Tissue A definitive diagnosis can be made when the number of organisms present is adequate and they are typical of the etiologic agent. For example, a spherule containing Fig. 3.7. Penicillium marneffei. Yeast showing

occasional transverse septa (center). Note absence of budding. GMS. [See color plate 7, following p. 48]. [Figure in color on CD-ROM]. 44 Michael B. Smith and Michael R. McGinnis endospores is characteristic of Coccidioides. To an inexperienced person, spherules could be confused with “parent bodies” that contain small, 5- to 7-μm round structures (which appear to represent altered erythrocytes) in myospherulosis. The sporangia of Prototheca species, Russell bodies, and closely appressed endospores may resemble the yeast form of B. dermatitidis. Chlorella species, which are green algae, may be confused with Coccidioides and Prototheca species in H&E stained tissue sections because their chlorophyll is destroyed during the fixation and embedding process. A green color due to chlorophyll can be readily seen in smears of fresh tissue. Because Coccidioides may form hyphae that develop into arthroconidia, and subsequently spherules, transition forms might be confused with a number of hyalohyphomycetes when spherules containing endospores are not evident. The type of etiologic agent present, the quality of the staining, the stains selected, and the skill of the pathologist contribute to the quality of the tissue diagnosis. 4. HOST RESPONSE Although there is no specific inflammatory tissue reaction associated with a particular fungus, some have characteristic inflammatory infiltrates or produce charac- teristic effects on tissue. For example, Blastomyces dermatitidis characteristically is seen with a mixed suppurative–granulomatous inflammatory infiltrate (Fig. 3.8). Several of the other thermally dimorphic pathogens, such as Coccidioides (Fig. 3.9) and Sporothrix schenckii (Fig. 3.10), can show similar reactions. Infections due to Fusarium species are usually seen with a suppurative inflammatory infiltrate, and often show angioinvasion with associated tissue infarction. A number of other opportunistic filamentous fungi will produce these identical findings in tissue. The inflammatory Fig. 3.8. Broad-based budding of Blastomyces dermatitidis in a background of neutrophils and histiocytes. H&E. [See color plate 8, following p. 48]. [Figure in color on CD-ROM]. 3. Diagnostic Histopathology 45 Fig. 3.9. Large spherule containing endospores of Coccidioides species. H&E. [See color plate 9, following p. 48]. [Figure in color on CD-ROM]. infiltrate associated with an infection is influenced not only by the infecting organism, but also by the immune status of the patient. A characteristic inflammatory infiltrate, seen with infection by a given organism in an immunocompetent patient, may not be present or may be altered in a severely immunocompromised individual. Fig. 3.10. Sporothrix schenckii with characteristic “cigar-shaped” buds attached by narrow base to the parent cell. GMS. [See color plate 10, following p. 48]. [Figure in color on CD-ROM]. 46 Michael B. Smith and Michael R. McGinnis Pyogenic inflammation, abscess formation, suppurative necrosis, and a propensity to invade blood vessels associated with hyaline, sparsely septate hyphae with irregular branching and large diameter are characteristic of Zygomycetes hyphae, such as Absidia, Mucor, Rhizomucor, and others (Fig. 3.11). Rarely, chlamydoconidia may be formed by species such as Rhizopus arrhizus. Occasionally Zygomycetes hyphae will stain positive with the Fontana–Masson stain. In contrast, a mixed purulent necro- tizing inflammation with hyaline septate, dichotomously branching hyphae having a consistent and uniform diameter is associated with Aspergillus species. If a cavity is present, the aspergilli often form conidial heads that allow for the identification of the Aspergillus to species. Some species such as A. terreus form lateral one-celled aleuri- oconidia along their hyphae in tissue (Fig. 3.12). When calcium oxalate crystals that originated from fungal oxalic acid are present near hyphae in necrotic tissue, A. niger should be considered. Aspergillus and Pseudallescheria boydii resemble each other in tissue, and often cannot be differentiated histologically. When conidial heads of Aspergillus species are seen in tissue, which usually occurs only in lesions exposed to air, such as in a lung cavity, a specific histopathologic diagnosis of aspergillosis can be rendered. Fig. 3.11. Hyphae of a Zygomycete. H&E. [See color plate 11, following p. 48]. [Figure in color on CD-ROM]. 3. Diagnostic Histopathology 47 Fig. 3.12. Hyphae of Aspergillus terreus with small, lateral aleurioconidia. GMS. [See color plate 12, following p. 48]. [Figure in color on CD-ROM]. 5. OTHER IMPORTANT CONSIDERATIONS The accuracy of a histopathologic examination of tissue sections is also impacted by a number of parameters that are out of the control of the histopathologist. The selection of the sample by the clinician or surgeon is crucial. The central portion, as well as the periphery of the lesion, is important because some fungi tend to be predominantly in one portion rather than the other. H. capsulatum tends to be in the central portion of lesions, whereas Blastomyces dermatitidis appears at the edge. Because fixatives used in histology kill fungi, a portion of the specimen must be concurrently sent to the mycology laboratory, where the fungi causing the infectious disease process can be isolated and identified. Important fungal pathogens and their morphology in tissue are summarized in Table 3.2. Often, presumptive identifications are made first via histopathology, with the definitive identification being delayed until the isolated fungus is identified in the laboratory (Fig. 3.13). Even if the etiologic agent cannot be identified, the tissue forms seen may result in the recognition of the disease and allow initiation of treatment. For example, granules are associated with mycetoma, muriform cells with chromoblastomycosis, and oval yeast cells and pseudohyphae with candidiasis. The fungal forms seen in tissue are extremely important in diagnosing the disease, even if they cannot be used to identify the specific fungus causing the disease. Simply determining the presence or 48 Michael B. Smith and Michael R. McGinnis Table 3.2 Typical characteristics of fungal structures found in human tissue Infection Fungal morphology Differential diagnosis Adiaspiromycosis Solitary cells, 200–400 μm, cell wall NA 10–80 μm, hyaline. Endosporulation, budding cells, and hyphae absent. Aspergillosis Hyphae, 2.5–6 μm, swollen cells up to Candidiasis (hyphae), 12 μm, dichotomous branching, hyalohyphomycosis septate, parallel walls, hyaline. (hyaline hyphae), Calcium oxalate crystals maybe phaeohyphomycosis present. Conidial heads may form (phaeoid hyphae), within cavities. Pseudallescheria boydii, occasionally zygomycetes. Blastomycosis Small yeast cells, 2–4 μm. Typical cells, Coccidioidomycosis 6–15 μm. Large yeast cells, 20–30 (endospores), μm. Single blastoconidia, broad cryptococcosis (small base between parent and daughter capsule form), cells, thick cell wall, consistent histoplasmosis. size, hyaline. Extracellular, more than one nucleus may be present. Pseudohyphae and hyphae may be present in areas of body with lower temperature (ears, upper airway). Yeast tends to be at edge of lesions. Candidiasis Yeast 2.5–6 μm, globose to ovoid. Aspergillosis (hyphae), Pseudohyphae. Hyphae may be blastomycosis (small yeast present, hyaline. form), cryptococcosis (small capsule), phaeohyphomycosis (pseudohyphae). Chromoblasto- Muriform cells, 5–12 μm, chestnut Phaeohyphomycosis. mycosis brown, crust-like material may be present on cells. Septate, branching, dematiaceous hyphae in epidermis. Coccidioidomycosis Spherules, 20–200 μm, endospores Blastomycosis, 2–5 μm. Hyphae, arthroconidia, cryptococcosis and developing spherules may be (small capsule form), present, hyaline. Portions of spherule protothecosis. wall often present. Cryptococcosis Yeast, 2–20 μm, globose, ovoid, Blastomycosis (small elliptical to crescent shaped, variable yeast form),candidiasis, in size, capsule. Narrow neck between histoplasmosis. parent and daughter cells. Melanin in cell wall stains with Fontana-Masson stain. (Continued) 3. Diagnostic Histopathology 49 Table 3.2 (Continued) Typical characteristics of fungal structures found in human tissue Infection Fungal morphology Differential diagnosis Histoplasmosis Yeast 2–5 μm, globose to ovoid, single Candidiasis, blastoconidium, intracellular, single cryptococcosis (yeast nucleus, hyaline. Halo between cell wall in histiocytes), and fungal cytoplasm in H&E stained Penicillium sections. Poorly stained cell walls in marneffei. calcified lesions (coin lesions). Yeast tends to be in center of lesions. Histoplasmosis Yeast 8–15 μm, globose to ovoid, single Blastomycosis (African variety) blastoconidium, intracellular, single (especially large nucleus, hyaline. Halo between cell wall yeast form). and fungal cytoplasm in H&E stained sections. Hyalohyphomycosis Hyphae 2.5–7 μm, septate, branching, may Phaeohyphomycosis. have swollen cells, hyaline. This is the non-pigmented counter part to phaeohyphomycosis. Lobomycosis Series of globose cells, 5–12 μm, thick Paracoccidioidomycosis. walls, narrow tubular connections, hyaline. Hyphae absent. Melanin in cell wall stains with Fontana-Masson stain. Typically in cutaneous-subcutaneous tissue. Paracoccidioidomycosis and lobomycosis often occur together in some geographic regions. Mycetoma Sclerotia (syn. grains, granules) 1–4 mm, Actinomycotic organized masses of hyphae. Hyphae 2–6 mycetoma, μm, often with swollen cells. Variable in botryomycosis. color. Paracoccidioido- Yeast 5–60 μm, globose to oval, multiple Blastomycosis, mycosis blastoconidia, attached by narrow tubular cryptococcosis connections; budded cells remain attached, (small capsule form), hyaline. Cell wall thick, especially central histoplasmosis, cells. Does not stain with Fontana-Masson lobomycosis. stain. Penicilliosis Yeast 2.5–4.5 μm, some cells 1–2 × 3 to 6 Histoplasmosis (Penicillium μm, globose to ovoid, division by fission, marneffei) hyaline. Blastoconidia absent. Intracellular. Phaeohyphomycosis Yeast, pseudohyphae, hyphae, or any Hyalohyphomycosis combination. Hyphae 2.5–6 μm, often with swollen cells up to 25 μm, pale brown to hyaline. Morphology extremely variable. (Continued) 50 Michael B. Smith and Michael R. McGinnis Table 3.2 Continued Infection Fungal morphology Differential diagnosis Protothecosis (algae) Sporangia 2–2.5 μm, 2–8 sporangiospores, Chlorella species, often with one central spore, hyaline. coccidioidomycosis. Hyphae and blastoconidia absent. Rhinosporidiosis Sporangia, 6 to >300 μm, mature Adiaspiromycosis, (protozoan) sporangiospores 6–7 μm, sporangial coccidioidomycosis. wall approximately 5 μm thick, hyaline. Sporotrichosis Yeast 2–6 μm, rarely up to 20 μm, Candidiasis, globose to ovoid (“cigar-shaped”), histoplasmosis. hyphae rare, hyaline. Zygomycosis Hyphae, 3–25 μm, sparsely septate, Aspergillosis, irregular diameter, irregular branching, hyalohyphomycosis, nonparallel walls, often distorted. Tend pythiosis. to invade blood vessels. absence of invasion of fungal pathogens by histopathology can influence a patient’s course tremendously. With close cooperation and communication between a patient’s physician, surgeon, and histopathologist, the microscopic assessment of fungi in tissue can make an important if not crucial contribution to a patient’s treatment and clinical course. Hyphae only Budding yeasts only Hyphae (or pseudohyphae) and yeasts Blastomyces, Candida glabrata, Cryptococcus, Septation present Histoplasma, Arthroconidia present Paracoccidioides, Sporothrix, other rare yeasts no yes yes no (aseptate) (septate) Agents of Dark cell walls on H&E (or Trichosporon, Candida (most zygomycosis Fontana-Masson staining) Blastoschizomyces species), Malassezia yes no Agents of Aspergillus or other agents phaeohyphomycosis of hyalohyphomycosis Fig. 3.13. Simple flow algorithm for diagnosis of fungal infection by histopathology. 3. Diagnostic Histopathology 51 SUGGESTED READINGS Chandler FW, Kaplan W, Ajello L. A colour atlas and textbook of the histopathology of mycotic diseases. London: Wolfe Medical Publications, 1980. Chandler FW, Watts JC. Pathologic diagnosis of fungal infections. Chicago: ASCP Press, 1987. Salfelder K. Atlas of fungal pathology. Boston: Kluwer Academic Publishers, 1990. Sheehan DC, Hrapchak BB. Theory and practice of histotechnology. 2nd ed. St Louis, MO: CV Mosby, 1980. 4 Diagnostic Immunology Samit S. Desai, MD and Brian Wong, MD 1. INTRODUCTION The frequency of invasive fungal infections has risen dramatically in recent years, primarily because of a larger population of at-risk patients who are immunocompro- mised, neutropenic, or critically ill. For clinicians evaluating these patients, it has become increasingly important to make the diagnosis early so that timely antifungal therapy can be instituted. Although culture of body fluids or tissue for the causative fungus continues to be the gold standard for definitive diagnosis, it may sometimes take several weeks to obtain results and the process often lacks sufficient sensitivity. For example, blood cultures are positive in only approximately 50% of cases of invasive candidiasis (IC) and in fewer than 10% of cases of invasive aspergillosis (IA) (1). A presumptive diagnosis can also be made on the basis of characteristic histopathology and special tissue stains. However, obtaining adequate samples from protected anatomical sites is often not feasible in the populations at highest risk for such infections. Non-culture-based diagnostic tests are classified into four groups according to which component of the invading pathogen or host immune response they target. These include detection of host antibody, fungal antigen, fungal metabolites, or fungal nucleic acid. Overall, despite these multiple potential targets and extensive efforts toward development, only a handful of non-culture-based tests have proven clinically useful, and even fewer have reached commercial availability. As current diagnostic techniques are less than ideal, development of new methods is a priority in medical mycology. This chapter outlines the available tests according to the component of the invading pathogen or host immune response they target and provides some discussion of their strengths and weaknesses. Given the growing interest in this field, an intro- duction to newer assays that are currently being investigated is included. Specific recommendations for utilizing the currently available tests in conjunction with the culture and histopathology are discussed for individual fungal species and specific disease manifestations. From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R.

Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 53 54 Samit S. Desai and Brian Wong 1.1. Antibody Testing Many tests in current use have been developed to detect host antibodies against specific fungal antigens. These require identification of one or more distinctive antigens to which host antibodies are directed, sufficient immunocompetence on the part of the host to mount a specific antibody response, and the use of a variety of techniques to detect the antibody, such as tube precipitin (TP) assays, immunodiffusion (ID) assays, complement fixation (CF) assays, radioimmunoassays (RIA), and enzyme- linked immunosorbent assays (ELISA/EIA). The major limitation of this general approach is that immunocompromised patients have impaired abilities to mount specific antibody responses. Moreover, these responses may be delayed and antibodies do not necessarily distinguish acute infection from chronic infection or colonization. 1.2. Antigen Testing A second common method to diagnose fungal infection includes tests that use immunologic reagents to identify antigenic components of the fungus. These require the presence of circulating antigenemia with unique antigens and use of a variety of techniques to detect the antigens, including latex agglutination (LA) assays, dot immunobinding assays, ELISA, and RIA. Monoclonal or polyclonal antibody is often needed in these assays to help detect the antigen of interest. The major limitations of this general approach are the low level and transient nature of antigenemia in some hosts, occasional cross-reactions between antigens derived from different fungal species, and lack of specificity for a particular antigen when polyclonal antibodies are used. 1.3. Metabolite Testing Another methodology includes the direct detection of fungal metabolites in patient serum or other samples. They are usually by-products of a specific fungus that are detected via gas chromatography, mass spectrometry, or an enzymatic reaction. One limitation of these tests is that the metabolic products are not unique to individual fungal species and may be present in small amounts in uninfected individuals. Further, the level of metabolite may not be present in sufficient quantity outside of the local tissue being invaded, making detection difficult. 1.4. Nucleic Acid Testing Most recently, tests that use nucleic acid amplification techniques to identify specific fungal nucleic acid sequences have been explored. The basic steps required are sample preparation, nucleic acid target selection, amplification, and detection of the amplified products. There is still significant debate among researchers as to how best to accom- plish each of these steps; however, there is consensus that this general approach has numerous advantages. First, fungal DNA or RNA may be amplified and detected even if viable fungal cells are not present. Second, the results can be generated within 4 to 8 hours of sample collection and even faster with some newer methods. Finally, the results may correlate well with disease burden and subsequent clinical outcome. Potential limitations of the technique include its possible inability to distinguish colonization from true infection and its potential false-positive results due to cross-contamination. 4. Diagnostic Immunology 55 2. PAN-FUNGAL (1,3--D-GLUCAN) TESTING 1,3--d-glucan (BG) is a major component of the cell walls of many different fungi. The ability of fungal BG to activate an enzyme in the clotting cascade of the horseshoe crab has led to the development of assays capable of detecting very small amounts of BG. Two separate assays, Fungitec-G test (Seikagaku Corp., Tokyo, Japan) and Fungitell™ assay (Cape Cod Assoc., East Falmouth, MA), have been developed for this purpose. The Fungitec-G test has shown high sensitivity and specificity when used prospectively to predict a fungal etiology for fever in high-risk populations (2) and also when tested retrospectively in patients with known invasive aspergillosis (3). The Fungitell assay has also shown good correlation when used retrospectively in patients with proven or probable fungal infections (4), but it has not been prospectively studied for its ability to predict or diagnose fungal infections. The major limitation of these tests is their inability to differentiate between different species of fungi, because BG is a component of the cell walls of Candida, Aspergillus, Trichosporon, Fusarium, and Saccharomyces species, though not of Cryptococcus or the agents of zygomycosis. False-positive results occur in patients exposed to other sources of BG such as dialysis membranes and filters, cotton gauze and sponges used in surgery, and some medications. 3. CANDIDIASIS Candida species are now the fourth most common microorganism isolated from the bloodstream of hospitalized patients in the United States and the sixth most common nosocomial pathogen overall (5). Rapid detection of IC is critical and warrants the development of nonculture diagnostic approaches. This goal has drawn much attention, but owing to limited results still requires further investigation. 3.1. Antibody Detection Antibody detection assays were the area of earliest interest but yielded tests with poor sensitivity and specificity. These tests have since fallen out of favor and are not recommended for routine use. 3.2. Antigen Detection Several tests that target a variety of cell-wall and cytoplasmic components have been developed to detect macromolecular Candida antigens (Table 4.1). Some of these are no longer available, such as an assay to detect enolase antigen. Of the available tests, the earliest was the Cand-Tec LA assay (Ramco Laboratories, Stafford, TX), which was designed to detect circulating Candida antigen in patients with serious, disseminated infection. Unfortunately, there are conflicting reports (6,7) on its overall sensitivity and specificity, especially in patients with renal failure or rheumatoid factor positivity, making it difficult to confirm the diagnosis of candidiasis by the Cand-Tec assay alone. The mannan component of the Candida cell wall is a major antigen and the target of many serum detection assays. These assays vary in the laboratory method and type of antibody used for detection. Two tests that use the same monoclonal antibody are the Pastorex Candida LA test (Bio-Rad, Marnes-la-Coquette, France) and the Platelia Table 4.1 Studies of immunological assays for Candida infection Target Assay Population tested Sensitivity Specificity Comments Ref. Antigen tests Retrospective analysis of 30/39 (77%) 35/40 (88%) Titer of 1:4 considered positive patients with candidemia (6) and controlpatients with Unknown superficial candidal Cand-Tec LAa colonization, other deep 16/39 (41%) 38/40 (95%) Titer of 1:8 considered positive mycosesand healthy subjects Prospective analysis of patients 16/23 (70%) 123/179 (69%) Titer of 1:4 considered positive at-risk for disseminated (7) candidiasis 7/23 (30%) 159/179 (89%) Titer of 1:8 considered positive Pastorex LAb As above 10/39 (26%) 40/40 (100%) (6) Retrospective analysis of 8/23 (35%) 150/150 (100%) Candidemia patients Mannan Pastorex LA patients with proven invasive candidiasis and control patients that included 4/20 (20%) Candida infection of (8) hospitalized, ICU patients, other sterile sites patients with other deep mycoses and healthy subjects. 11/23 (42%) 147/150 (98%) Candidemia patients Platelia EIAc As above (8) 7/20 (35%) Candida infection of other sterile sites Platelia Ag/Ab EIAb 19/23 (83%) 140/150 (93%) Candidemia patientsAs above 17/20 (85%) Candida infection of (8) other sterile sites Prospective analysis 6/7 (86%) 59/59 (100%) Autopsy proven of febrile mostly invasive deep Fungitec-G testd hematology-oncology mycosis (2) patients and a small 23/24 (96) Fungemia patients population of patients 1/2 (50%) Fungal catheter- with other chronic related infection illnesses (unable to 2/2 (100%) Fungal meningitis differentiate Candida 5/6 (83%) Other fungal sub-group information) infections 1,3--d-glucan 76/92 (83%) 148/170 (87%) Candidemia pts. at BG cut-off of 60 pg/ml Retrospective analysis of Fungitelle patients with proven or 11/15 (73%) 157/170 (92%) Other Candida infections (4) probable invasive fungal at BG cut-off 60 pg/ml infections and healthy 72/92 (78%) Candidemia pts. at BG controls (only proven cut-off of 80 pg/ml Candida infection data 11/15 (73%) Other Candida infections shown here) at BG cut-off 80 pg/ml (Continued) Table 4.1 (Continued) Target Assay Population tested Sensitivity Specificity Comments Ref. Metabolic tests Prospective analysis of 31/42 (74%) 178/206 (86%) Candidemia high risk oncology patients Enzymatic- patients and control d-arabinitol chromogenic patients that included 25/30 (83%) Persistent (9) those with fever, candidemia neutropenia, and patients mucosal colonization with Candida but no 4/10 (40%) Invasive tissue culture evidence of candidiasis w/o IC, and those without candidemia these and also without culture 7/16 (44%) Deep mucosal evidence of IC. candidiasis patients 63/83 (76%) 89/100 (89%) Candidemia patients (10) Enzymatic- Retrospective evaluation of 25/30 (83%) Persistent candidemia fluorometric patients with candidemia and patients healthy control patients BG, 1,3--d-glucan. aRamco Laboratories, Stafford, TX. bBio-Rad, Marnes-la-Coquette, France. cBio-Rad, Munich, Germany. dSeikagaku Corp., Tokyo, Japan. eCape Cod Assoc., East Falmouth, MA. 4. Diagnostic Immunology 59 Candida EIA test (Bio-Rad, Munich, Germany). Although the EIA test is more sensitive than the LA test, they are both limited by the rapid clearance of mannan antigenemia. In an effort to overcome this, a combination EIA test was developed to detect mannan antigen and anti-mannan antibodies simultaneously, marketed as the Platelia Candida Antibody and Antigen test (Bio-Rad, Marnes-la-Coquette, France). When this test was used retrospectively in high-risk patients with proven invasive candidiasis and control patients who included hospitalized patients without Candida infections, patients with other deep-seated mycoses and normal healthy patients, this combination test showed a sensitivity of 80% and specificity of 93% (8). 3.3. Detection of Fungal Metabolites d-Arabinitol (DA) is a five-carbon polyol metabolite that is produced by several pathogenic Candida species (except for C. krusei and C. glabrata). It has been shown to be present in higher serum concentrations in humans and animals with IC than in uninfected or colonized controls, making it potentially useful as a diagnostic marker for IC. There are two general methods to measure DA: gas chromatography or an enzymatic method. The former is labor intensive and not readily available in most hospital labs, while the latter is more suited to a commercial test kit, as is currently marketed in Japan as Arabinitec-Auto (Marukin Diagnostics, Osaka, Japan). This assay is also available for DA testing on urine samples. Several studies have shown that DA can be detected earlier than Candida in blood cultures and that serial measurements correlate well with clinical response to therapy (9,10). 3.4. Nucleic Acid Detection Many different methods have been developed and studied with promising results, but each has different limitations, such as sensitivity, specificity, reproducibility, cost, or commercial availability. 3.5. Conclusions and Recommendations Tests being investigated are promising as additional diagnostic strategies in the detection of IC. In general, there does seem to be utility in the tests for mannan antigen/antibody, serum BG, and serum DA as adjunctive tests in combination with cultures, histopathology, and radiology. As yet, no single test has been demonstrated to have optimal sensitivity and specificity. Several studies have compared these tests with one another, with variable results, differences in methodology, and small sample populations making it difficult to draw any conclusions. Their greatest value appears to be in serial testing of high-risk populations in which the trend (rather than a single value) will improve sensitivity, help make an earlier diagnosis, and monitor the effectiveness of empirically instituted antifungal therapy. A potential strategy would be the use of two or more of these tests in combination to further improve accuracy in making the correct diagnosis. For now, these modalities can only be recommended as supplements and cannot be relied on as sole diagnostic methods. Further, rigorous, prospective clinical trials are needed to determine which will offer the greatest clinical utility. 60 Samit S. Desai and Brian Wong 4. ASPERGILLOSIS There are a variety of clinical manifestations of Aspergillus infection including aspergillomas, allergic bronchopulmonary aspergillosis (ABPA), chronic invasive aspergillosis, and IA. Different types of immunologic tests have shown different utility for this spectrum of disease. 4.1. Antibody Detection The diagnosis of aspergilloma is made by combined radiologic and serologic testing, where immunoglobulin G (IgG) antibodies are usually positive. Similarly, for ABPA, a combination of routine blood tests, radiographic findings, skin testing for Aspergillus sensitivity, and both IgG and IgE antibody positivity are used for diagnosis. Conversely, antibody detection is less useful and not recommended for invasive disease because the immunocompromised patients most at risk are less likely to mount a sufficient response. 4.2. Antigen Detection Galactomannan (GM) is a polysaccharide component of the Aspergillus cell wall. It has been demonstrated in the sera of patients with IA and thus has been the target of several serum detection assays. These assays vary in the laboratory method and antibody type used for detection. An earlier test called the Pastorex Aspergillus (Bio- Rad, Hercules, CA) utilized an LA method with a monoclonal antibody. It yielded disappointing results with low sensitivity unless multiple samples were

used and false- positive reactions from cross-reactivity of the antibody with several other fungal species (11,12). A newer, commercially available test is the Platelia Aspergillus (Bio-Rad, Hercules, CA). This sandwich ELISA uses the same monoclonal antibody but has the ability to detect GM at much lower limits, thereby improving the test’s sensitivity and allowing earlier detection of IA. In a retrospective review of stored specimens on bone marrow transplant and leukemia patients, the study leading to its FDA approval, this assay had a sensitivity of 81% and specificity of 89% (13). Several prospective studies have tested it on a variety of patients, from those with hematopoietic stem cell transplants to those with neutropenic fevers, with variable results (14,15). False- negative results can occur due to limited angioinvasion, low fungal load, high antibody titers, or the use of prophylactic or preemptive antifungals. Alternatively, false positives occur due to cross-reactivity of the assay with other fungal species, certain bacterial exoantigens, or several fungal-derived antibiotics. Although it can be detected in other body fluids, the GM assay is validated only for serum samples at this time (Table 4.2). 4.3. Detection of Fungal Metabolites Mannitol, a six-carbon acyclic polyol, is produced in large amounts by many different fungi, including several Aspergillus species in culture. Unfortunately, available data do not support the usefulness of mannitol as a diagnostic marker. 4.4. Nucleic Acid Detection While DNA detection assays for Aspergillus have had mixed results, mRNA detection assays have shown more promise but still need further evaluation (17). Table 4.2 Studies of Aspergillus galactomannan antigen detection Assay Population tested Sensitivity Specificity Comments Ref. Pastorex LAa Retrospective analysis of Prov/Prob 7/10 (70%) 44/51 (86%) Single positive test was (11) at-risk neutropenic patients considered true positive Platelia ELISAa As above Prov/Prob 9/10 (90%) 36/51 (71%) ELISA was able to detect (11) IA earlier then LA Retrospective analysis of Prov 4/25 (16%) 169/169 (100%) Single positive test was (12) Pastorex LA bone marrow transplant Prob 7/15 (47%) considered true positive recipients Poss 0/8 (0%) Prov 19/25 (76%) 138/169 (82%) ELISA was able to detect Platelia (12) As above Prob 14/15 (93%) IA earlier than LA ELISA Poss 8/8 (100%) earlier than LA Prospective monitoring of Prov 17/18 (94%) 72/73 (99%) ELISA was able to detect IA (14) Platelia hematopoietic stem cell Prob 0/0 (0%) earlier than by other means. ELISA transplant patients Poss 0/6 (0%) Consecutive positives were considered true positive Platelia ELISA Retrospective analysis of Prov/Prob 5/9 (56) 31/33 (94%) Consecutive positive were (16) orthotopic liver transplant considered true positive recipients (Continued) Table 4.2 (Continued) Assay Population tested Sensitivity Specificity Comments Ref. Prospective monitoring of Prov 0/3 (0%) 748/751 (100%) Consecutive positive were (15) Platelia hematology- oncology and Prob 17/31 (55%) considered true positive ELISA intensive care unit patients Poss 14/22 (64%) Platelia ELISA Retrospective analysis of Prov/Prob 25/31 132/148 (89%) (13) bone marrow transplant (81%) and leukemia patients (including children) Prov, proven; Prob, probable; Poss, possible. aBio-Rad, Hercules, CA. 4. Diagnostic Immunology 63 4.5. Conclusions and Recommendations Despite the broad spectrum of disease caused by Aspergillus organisms, it is the invasive disease that is most important and most challenging diagnostically. While nucleic acid detection assays seem to hold some promise, only the Platelia Aspergillus GM assay can currently be recommended to support a diagnosis of IA in the appropriate clinical setting. This test has shown increased specificity with serial sampling and can be used to screen patients on a twice weekly basis during periods of severe immunosuppression or to monitor patients once or twice weekly while they are on therapy. All clinicians should keep in mind the potential for false-positive and false- negative results and incorporate the GM results into the general clinical assessment of the patient, rather than as the sole basis on which to change management. For instance, a change in the assay from negative to positive in an immunosuppressed patient under surveillance should prompt a more thorough investigation for IA, while a change from positive to negative should lend support to other evidence that proper therapy has been instituted. In addition, it is important to remember that the positive predictive value of this test is highest in populations with a high pretest probability; using it for routine diagnosis in lower risk populations will likely increase the chance that a positive result is a false positive. Despite its limitations, this assay is a suitable, noninvasive adjunct for diagnosing and managing IA (Box 4.1). Box 4.1. Recommendations for using Aspergillus galactomannan antigen assay 1. Twice weekly monitoring of patients during periods of severe immunosuppression 2. Retesting of any positive results during this time period to improve specificity 3. For patients presenting with compatible clinical findings, use it as an adjunct in making a diagnosis 4. Once treatment is initiated, use it to monitor response to treatment (usually once a week) 5. Always interpret the results in the context of other clinical and laboratory findings 5. CRYPTOCOCCOSIS Culture and histopathology remain the gold standards for diagnosing cryptococcal disease. An alternate method is serologic tests, which have the advantage of more rapidly establishing a diagnosis and allowing initiation of treatment. 5.1. Antibody Detection Tests for cryptococcal antibodies are not useful and are not widely available for clinical use because they have high false-positive and false-negative rates. 5.2. Antigen Detection Some of the most important and rapid serodiagnostic tests available for any fungi are those used to detect the cryptococcal capsular polysaccharide antigen (Table 4.3). These tests utilize a variety of different laboratory techniques for antigen detection. In a comparison study of four LA assays and one ELISA assay, they all performed Table 4.3 Studies of Cryptococcus antigen detection Assay Population tested Sensitivity Specificity Comments Ref. Crypto LAa 182 CSF/90 serum samples. CSF 100% CSF 98% 19 CSF/30 serum positive Serum 83% Serum 98% (18) by culture (48 from HIV patients). CSF 100% CSF 97% Myco-Immune LAb Risk factors of patients with Serum 83% Serum 100% negative results not noted Immy Latex-Crypto CSF 93% CSF 93% Uses pronase on Antigenc Serum 97% Serum 93% CSF/serum Calas Latex-Crypto CSF 100% CSF 96% (18) Antigend Uses pronase on serumSerum 97% Serum 95% Premier EIAd CSF 100% CSF 98% Serum 93% Serum 96% Unknown assay Case report—2 patients with 2/2 (100%) 12/12 (100%) Cryptococcus in pleural (20) fluid and analysis of pleural effusions in a group of controls for cryptococcal antigen Retrospective CSF 9/9 (100%) 2997/3000 (100%)(Of 3 Immunocompromised Crypto-LAa or Crypto- review—multiple samples, positives—1 patients (21) Teste 9 immunocompetent/4 immune immunocompromised compromised, 2 Immunocompetent patients with cryptococcal CSF 3/13 (23%) immune competent) patients meningitis and a large group of uninfected patients Retrospective review—42 CSF 3/12 (25%) Immunocompromised HIV-negative patients with Serum 7/15 (47%) patients Unknown assay (22) pulmonary Cryptococcus (6 patients with disseminated infection) CSF 0/3 (0%) Immunocompetent Serum 0/3 (0%) patients aInternational Biological Labs, Cranbury, NJ. bAmerican MicroScan, Mahwah, NJ. cImmuno-Mycologics, Norman, OK. dMeridian Diagnostics, Cincinnati, OH. eBioproducts, Walkersville, MD. 66 Samit S. Desai and Brian Wong well when used to analyze cerebrospinal fluid (CSF) samples of predominantly human immunodeficiency virus (HIV)-positive patients (18). The same study also showed good results for antigen detection in serum samples, but only with the ELISA and the two pronase pretreated LA assays. It is well known, however, that all of these assays are less sensitive when used in immunocompetent patients. One advantage in either patient population is the quantitative nature of the antigen tests, with higher titers generally indicating a higher burden of organisms. This also gives prognostic information such that titers of 1:32 or greater are found in 90% of patients with ultimately fatal infections, but in only 10% of those who are eventually cured of their infection; and titers of 1:8 or greater at the end of treatment are associated with a higher incidence of relapse (19). These tests can also be used to analyze pleural fluid samples in patients with suspected cryptococcal pneumonia (20). The only limitation of these assays is occasional false- positive results, generally in low titers, in patients with disseminated trichosporonosis, Capnocytophaga canimorsus sepsis, and Stomatococcus infection. 5.3. Detection of Fungal Metabolites Cryptococcus species, like Aspergillus species, also produce large amounts of mannitol, but it has not proven useful as a diagnostic marker for this disease either. 5.4. Nucleic Acid Detection Several studies have shown the feasibility of using polymerase chain reaction (PCR) technology to diagnose Cryptococcus infections (23,24). Although these findings are encouraging, they have not been fully evaluated to establish sensitivity, specificity, and role in clinical management of patients with suspected cryptococcal disease. 5.5. Conclusions and Recommendations Cryptococcal infection is the rare condition in which a serodiagnostic test has proven not only to have sufficient sensitivity and specificity, but also to have good clinical correlation. Several kits are commercially available. Although a positive cryptococcal antigen result is highly suggestive of infection and can be the sole basis for initiating targeted therapy, definitive proof of disease still does require culture or histopathology and efforts to prove the diagnosis by these means are always warranted. The clinical utility of these antigen tests is different for acquired immunodeficiency syndrome (AIDS) patients and immunocompetent patients. For AIDS patients with suspected meningeal disease who are able to undergo a lumbar puncture (LP), the CSF antigen test should be used to make a rapid, accurate diagnosis. In patients unable to undergo an LP or with vague central nervous system symptoms not warranting an LP, a serum antigen test may be used as a substitute for screening because it has sensitivity comparable to that of a CSF test in this setting. If the serum test is positive, indicating disseminated disease, the CSF opening pressure should be checked (if no other contraindications exist), as this has implications for management. A pleural fluid antigen titer can also be checked if pneumonia is suspected. In addition, the baseline and end treatment antigen titers are helpful for prognostic purposes. However, serial measurement of antigen titers during therapy is not recommended in this patient population, in whom these fluctuations do not accurately correlate with clinical response. This is especially true for serum specimens. 4. Diagnostic Immunology 67 In immunocompetent patients, because both the CSF and serum assays have a lower sensitivity, both tests should be utilized if meningitis is suspected; pleural fluid can also be tested if pneumonia is suspected. Further, because this population is more capable of clearing antigenemia, serial measurement of antigen titers while on therapy (generally at 2-week intervals) may be useful for documenting therapeutic response and predicting relapse. As is the case for AIDS patients, the baseline and end treatment antigen titers provide useful prognostic information. In both patient populations, care must be taken not to compare titers derived from different kits given the lack of standardization among manufacturers (Box 4.2). Box 4.2. Recommendations for using cryptococcal antigen tests in different populations AIDS patients 1. For meningeal symptoms, check a cerebrospinal fluid antigen. If unable to do lumbar puncture, can check serum antigen 2. For non-meningeal symptoms, check a serum or site-specific antigen (i.e., pleural fluid) 3. A positive serum antigen suggests disseminated disease (including meningeal involvement) and a lumbar puncture should be done to measure opening pressure, which is important for management 4. Antigen titers correlate with disease burden and provide prognostic information, but should not be followed serially during therapy NON-IMMUNOSUPPRESSED PATIENTS 1. For meningeal symptoms, check both CSF and serum antigens 2. For non-meningeal symptoms, check a serum or site-specific antigen (i.e., pleural fluid) 3. Antigen titers correlate with disease burden, provide prognostic information, and can be followed at 2- week intervals during therapy to document therapeutic response and predict relapse 6. HISTOPLASMOSIS The standard method for the diagnosis of histoplasmosis remains isolation and specific identification of the causative organism. The process can take 2 to 4 weeks and the necessary specimens can be difficult to obtain. Immunologic tests offer a more rapid alternative, and in some manifestations of the disease are the preferred means of establishing a diagnosis. 6.1. Antibody Detection The two Histoplasma capsulatum species-specific antigens against which host antibodies are made are the H and M antigens. Antibodies against H antigen form during active histoplasmosis, while antibodies against M antigen may be formed in active or chronic histoplasmosis and are usually the first to arise on seroconversion (Table 4.4). These antibodies can be detected via either

ID or CF assays, where ID is 68 Samit S. Desai and Brian Wong Table 4.4 Studies of Histoplasma antigen and antibody detection Assay Patients with Patients Patients without Controls Specimen Ref. AIDS and without AIDS DH(limited DH with DH disease) Antigen RIAa 19/27 (70)b 2/4 (50) 0/122 (0) BAL fluid 25/27 (93) 0/122 (0) Urine (26) 23/26 (89) 0/122 (0) Serum 3/4 (75) 2/10 (20) 1/28 (4) CSF 3/4 (75) 4/10 (40) Urine (27) 2/4 (50) 2/10 (20) Serum 75/79 (95) 22/27 (82) 24/82 (29) Urine (28) 54/63 (86) 7/11 (64) 6/26 (23) Serum 38/40 (95) 12/16 (75) 11/30 (37) 1/96 (1) Urine (25) EIAa 38/40 (95) 12/16 (75) 11/30 (37) 1/96 (1) Urine (25) Antibody IDc 32/52 (62) 14/21 (67) 65/81(80) Serum (28) 17/21 (81) 210/255 (82) 4/767 (1) Serum (29) CFd 29/46 (63) 14/22 (64) 75/83 (90) Serum (28) 0/3 (0) 7/10 (70) CSF (27) 0/3 (0) 8/9 (89) Serum 12/21 (57) 212/255 (83) 15/357 (4) Serume (29) 17/21 (81) 197/255 (77) 8/357 (2) Serumf DH, disseminated histoplasmosis; RIA, radioimmunoassay; EIA, enzyme immunoassay; ID, immun- odiffusion; CF, complement fixation. aMira Vista Diagnostics, Indianapolis, IN. bNumber of positive tests/total number of subjects (%). cMeridian Diagnostics, Cincinnati, OH. dImmuno-Mycologics, Norman, OK; 1:8 or greater titer considered positive for CF testing. eAntibody to yeast phase antigen. f Antibody to mycelial phase antigen. more specific and CF is more sensitive. Antibodies against M antigen are detected 6 to 8 weeks after exposure in 50% to 80% of patients, but can persist for years in patients who have recovered from infection; therefore their presence does not distinguish remote infection from current disease. On the other hand, antibodies against H antigen are detected in only 10% to 20% of exposed patients, but their presence signifies an active 4. Diagnostic Immunology 69 infection. In general, asymptomatic patients are less likely to have detectable antibody levels, and if present, they are usually in lower titers. This is evidenced by the low levels of antibody detected in approximately 10% of healthy patients residing in an endemic area. Antibody titers generally decline over several months after exposure, but may remain positive for years in some chronic forms of the disease. False-negative results can occur in immunocompromised patients approximately 50% of the time and less frequently in other patients during the early stages of infection. False-positive results occur in approximately 15% of patients, mainly due to cross-reaction with the agents of coccidioidomycosis or blastomycosis. 6.2. Antigen Detection One of the major developments in diagnostic strategies for histoplasmosis was the introduction of antigen detection assays that could recognize a histoplasmosis polysac- charide antigen (Table 4.4). Depending on the disease manifestation, this antigen can be present in urine, serum, CSF, or bronchoalveolar lavage (BAL) fluid. The original assay was an RIA that was costly and posed a risk to laboratory personnel because of its radioactivity. The newer assay is an EIA test (Mira Vista Diagnostics, Indianapolis, IN) that uses a monoclonal antibody and has shown results similar to the RIA test (25). Antigen detection assays are especially useful for establishing a diagnosis in immunosuppressed patients and patients with acute disseminated forms of disease. Further, these tests are useful for monitoring antigen levels during treatment, where levels decrease with appropriate therapy and increase with disease relapse. Some cross-reactivity of the assay can be seen with penicilliosis, paracoccidioidomycosis, or blastomycosis. False-negative results can also occur depending on the population tested and the severity of illness. 6.3. Detection of Fungal Metabolites No tests of this nature are currently available. 6.4. Nucleic Acid Detection Preliminary studies support the feasibility of molecular approaches to the diagnosis of histoplasmosis and suggest that PCR and DNA probes might improve the accuracy for identifying H. capsulatum in tissues or body fluids. But these methodologies have not been validated by comparison with culture or antigen detection tests (30). 6.5. Skin Testing Skin testing with histoplasmin antigen is a useful epidemiologic tool to document past exposure and to investigate histoplasmosis outbreaks. It is of little use in the diagnosis of individual cases. Prior skin test positivity can be lost with disseminated disease or immunosuppression. 6.6. Conclusions and Recommendations Immunodiagnostic tests for histoplasmosis are a proven adjunct to the usual diagnostic methods of culture and histopathology (Table 4.5). Because of the wide spectrum of disease with histoplasmosis, there are different recommendations to help 70 Samit S. Desai and Brian Wong Table 4.5 Immunologic tests in different nondisseminated clinical manifestations of histoplasmosis Disease Antigen sensitivity Antibody Recommendations manifestations sensitivity 1. Acute localized <40% overall >80% when both Antibody testing is pulmonary IDand CF tests preferred method. histoplasmosis (with are done (at 4–6 Send both ID and CF possible sequelae weeks) antibody tests. of mediastinal granuloma, pericarditis, and rheumatologic syndromes) 2. Acute diffuse ∼90% in urine, 60–80% Antigen testing of serum reticulonodular or ∼70% in serum, and urine is preferred miliary pulmonary less frequently method. histoplasmosis in other sterile Antibody testing will body fluids identify remaining cases. In routine clinical practice, should send both to speed the diagnostic process. 3. Chronic ∼20% 90–100% Sputum or BAL fluid for pulmonary culture are preferred. histoplasmosis Can use antibody test for remaining cases. 4. Fibrosing Antigen test is 50–65% Antibody testing is mediastinitis, usually negative preferred method. broncholithiasis, Send both ID and CF asymptomatic lung antibody tests. granulomas, and chronic mediastinal lymphadenopathy 5. Histoplasma ∼20–70% in 0–70% in CSF, Antigen testing in CSF, meningitis CSF, ∼40–70% 0–80% in serum serum, and urine plus in urine, antibody testing in serum ∼20–50% in and CSF (use CF assay). serum Data and recommendations from refs. 24–29. 4. Diagnostic Immunology 71 guide the appropriate use of immunologic tests. Patients with acute localized disease and a low burden of organisms or patients with chronic sequelae of a prior histoplas- mosis infection should be diagnosed predominantly via antibody testing. Conversely, patients with acute diffuse disease and a high burden of organisms are most amenable to antigen testing. Although urinary antigen detection is the most sensitive for these patients as a whole, CSF and BAL fluid testing may prove more valuable in patients with disease at those specific sites. A third category of patients, those with chronic pulmonary histoplasmosis, can usually be diagnosed by routine cultures of sputum or BAL fluid. Antibody tests can be used if these cultures are negative. Clinicians should use caution when using serial antigen testing to follow disease progression; concurrent testing of both the prior and the current specimens is essential to counter the assay-to-assay variability. 7. BLASTOMYCOSIS A high level of suspicion for Blastomyces infection is important to its successful diagnosis because no clinical syndrome is characteristic for infection with this organism. While definitive diagnosis requires the growth of the organism from clinical specimens, a presumptive diagnosis can be made by histological characteristics and further supportive evidence can be gained from immunologic tests. 7.1. Antibody Detection Early serologic tests for blastomycosis were directed toward detecting host antibodies against B. dermatitidis A antigen. These tests utilized different laboratory techniques including ID, CF, and ELISA. The ID test has the most specificity and the ELISA test has the most sensitivity. However, all the tests have limited sensitivity for diagnosing acute disease because the mean peak seroprevalence of antibody occurs 50 to 70 days after the onset of symptoms (31). An additional limitation is the presence of detectable antibodies for 1 year or more even after successful treatment. Antibody detection assays directed against the WI-1 antigen of the outer cell wall of B. dermati- tidis have also been explored with promising results, but are not currently available commercially (32). 7.2. Antigen Detection An antigen detection assay for use on urine specimens of patients with suspected blastomycosis is also available (Mira Vista Diagnostics, Indianapolis, IN). This assay targets a glycoprotein antigen that unfortunately is not genus specific. Although it has a sensitivity of 93%, the specificity is only 79% owing to significant cross-reactivity of the assay with histoplasmosis, paracoccidioidomycosis, and penicilliosis (33). 7.3. Detection of Fungal Metabolites No tests of this nature are currently available. 7.4. Nucleic Acid Detection While nucleic acid detection assays have been examined in epidemiologic studies of blastomycosis, they have not been evaluated in clinical specimens of such cases. 72 Samit S. Desai and Brian Wong 7.5. Conclusions and Recommendations Several clinical features of blastomycosis make serodiagnosis relatively less important. Unlike histoplasmosis or coccidioidomycosis, in which many of the recog- nized cases are acute pulmonary infections with negative sputum smears and cultures, identified blastomycosis cases are usually chronic pulmonary infections or dissemi- nated infections of the skin and bones. In both of these conditions, histopathology and cultures are usually positive and easy to acquire. Further, despite the availability of multiple assays to detect Blastomyces antibodies or antigens, their sensitivities and specificities vary significantly and they are generally not helpful for diagnosing blasto- mycosis. Therefore, a negative test should never be used to rule out disease, nor should a positive test be an indication to start treatment. 8. COCCIDIOIDOMYCOSIS Culture and histopathology are the gold standards for diagnosing coccidioidomy- cosis, but have several limitations. First, although Coccidioides species are readily cultured, the culture needs to be performed under Biosafety Level 2 conditions and poses a certain degree of risk to laboratory personnel. Second, because Coccid- ioides species are listed by the Centers for Disease Control (CDC) as potential bioterrorism threats, laboratories working with these fungi must follow extensive security practices (and work under Biosafety Level 3 practices). Third, direct examination of clinical specimens is an insensitive test because of the small number of Coccidioides organisms present in most clinical specimens. Finally, the mycelial form of growth rarely allows microscopic identification of Coccid- ioides species, requiring further testing to detect coccidioidal antigen in the fungal extract or a specific ribosomal RNA sequence using a DNA probe. This often has to be carried out by a reference laboratory. Given these limitations, immunologic tests are an important adjunct in helping to establish a diagnosis of coccidioidomycosis. 8.1. Antibody Detection Serologic diagnosis of coccidioidomycosis is based on the detection of anti- coccidioidal antibodies via one of several different laboratory methods (Table 4.6). One such method, the tube precipitin (TP) assay, detects IgM antibodies directed against a heat-stable carbohydrate antigen of the fungal cell wall. These antibodies form relatively early during infection, with approximately 90% of patients developing them in the first 3 weeks of symptomatic disease. For patients with a self-limited illness, these antibodies decline to less than 5 percent within 7 months. A second method, the CF assay, detects IgG antibodies to the chitinase antigen, an enzyme of the fungal cell wall. These antibodies are detected later and persist longer. This assay can also be applied to body fluids other than serum; for example, it detects antibodies in CSF specimens of approximately 60% of patients with coccidioidal meningitis (34–36). The antibody concentrations measured by CF are expressed as titers and generally reflect the extent of infection. As variation between testing results from facility to facility exists, it is suggested that serial measurements be conducted using the same Table 4.6 Studies of Coccidioides antibody detection Assay Population tested Sensitivity Specificity Comments Ref. Retrospective analysis of antibody detection in 2524/3219 (78%) Pulmonary disease serum of a large group of patients with various (37) TP forms of coccidioidal infection 89/226 (39%) Disseminated disease 33/73 (45%) Meningeal disease Retrospective analysis of HIV patients with 3/7 (43%) (38) coccidioidal infection As above 1790/3219 (56%) Pulmonary disease 222/226 (98%) Disseminated disease (37) 69/73 (95%) Meningeal disease As above 5/7 (71%) (38) Retrospective analysis of patients with chronic 5/6 (83%) Dialysis patients CF (39)renal failure 14/18 (78%) Renal transplant patients Retrospective analysis of patients with 29/30 (97%) Serum samples (34) coccidioidal meningitis 25/30 (83%) CSF samples Retrospective analysis of HIV patients with 6/8 (75%) Serum samples (35) disseminated coccidioidal infection 4/6 (67%) CSF samples (Continued) Table 4.6 (Continued) Assay Population tested Sensitivity Specificity Comments Ref. Retrospective analysis of antibody detection in 0/9 (0%) 13/13 (100%) Pulmonary disease CSF of a group of patients with various forms (36) of coccidioidal infection and control patients without coccidioidomycosis 0/2 (0%) Disseminated disease 14/33 (42%) Meningeal disease 0/9 (0%) 13/13 (100%) Pulmonary disease IDCFa As above 1/3 (33%) Disseminated disease (36) 10/19 (53%) Meningeal disease Retrospective analysis of patients with proven 47/47 (100%) 362/362 (100%) (40) coccidioidomycosis infection and control

patients with non-coccidioidal pulmonary illness, other fungal illness, HIV disease and no illness. EIAb 43/47 (92%) 352/362 (97%) IgG aloneAs above 36/47 (77%) 354/362 (98%) IgM alone (40) 47/47 (100%) 347/362 (96%) IgG and IgM together 8/9 (89%) 0/13 (0%) Pulmonary disease LA As above 3/3 (100%) Disseminated disease (36) 31/33 (94%) Meningeal disease TP, tube precipitin; CF, complement fixation; ID CF, immunodiffusion using complement fixation antigen; EIA, enzyme immunoassay; LA, latex agglutination. aImmuno-Mycologics, Norman, OK. bMeridian Diagnostics, Cincinnati, OH. 4. Diagnostic Immunology 75 laboratory to allow comparison. Use of serial testing can help the clinician gauge disease progression, remission, or cure. Newer assays involve ID, ELISA, and LA techniques. The commercially available IDTP and IDCF tests (Meridian Diagnostics, Newtown, OH and Immuno-Mycologics, Norman, OK) can use a single prepared specimen to detect (with greater sensitivity) the same IgM and IgG antibodies previously detected by the individual TP and CF assays. The ELISA assay (Meridian Diagnostics, Cincinnati, OH) is highly sensitive for detecting IgM and IgG antibodies in serum or CSF, but its specificity is compro- mised by some false-positive reactions on CSF specimens and with IgM detection. The LA assay is commercially available, easy to use, and provides rapid results, but is limited by a higher number of false-positive reactions compared to the other assays. 8.2. Antigen Detection Research laboratories have demonstrated the ability to detect coccidioidomycosis antigen in both acute and chronic disease (41). Currently these tests remain a research interest rather than a clinically applicable procedure. 8.3. Detection of Fungal Metabolites No tests of this nature are currently available. 8.4. Nucleic Acid Detection Although studies have demonstrated the feasibility of DNA or RNA detection via PCR techniques in the diagnosis of coccidioidomycosis, this is still of limited utility as PCR positivity appears to be transient (42). 8.5. Skin Testing Skin testing with coccidioidin antigen or spherulin antigen is a useful epidemiologic tool to document past exposure. It may also be useful in patients in whom pulmonary coccidioidomycosis has already been proven by other means. A negative skin test in such a patient may be a bad prognostic sign, suggesting current or impending dissemination. Standardized, FDA-approved antigen is not currently available. 8.6. Conclusions and Recommendations The manifestations of most early coccidioidal infections overlap with those of other respiratory infections; therefore, specific laboratory testing is usually required to establish a diagnosis of coccidioidomycosis. Serologic tests are important in the diagnosis of these diseases as specific anti-coccidioidal antibodies develop in many, if not most, patients; though they are often not detectable in the first few weeks or even months after disease onset or in severely immunocompromised hosts. For this reason, the absence of detectable anti-coccidioidal antibodies does not generally exclude the diagnosis of coccidioidomycosis. For most patients who resolve their infection, the antibody concentrations decrease to undetectable levels during the course of illness, so measurable antibodies are more likely to represent a recent or active illness. In general, the commercial ID kit is the most often used assay while the old CF assay is generally 76 Samit S. Desai and Brian Wong reserved for specimens other than serum, such as CSF, pleural fluid, peritoneal fluid, or joint fluid. In any assay, repeat testing will improve the diagnostic yield. 9. PARACOCCIDIOIDOMYCOSIS A definitive diagnosis of paracoccidioidomycosis requires either direct visualization of the organism in body fluids or tissues or its isolation and growth in culture. Immunologic assays are useful and rapid adjuncts for diagnosing this infection, but unfortunately they are not available in the United States. 9.1. Antibody Detection Initial efforts at antibody detection utilized cytoplasmic extracts and cell wall compo- nents as antigen targets. But these antigens caused significant cross-reactivity with other fungal pathogens, leading to the discovery of more specific P. brasiliensis antigens. Using these newer antigens, many antibody detection assays have been developed. The major limitation of these different assays is that antibodies can be detected for years after apparent successful therapy, so their presence does not help determine disease activity. In addition, there is still some cross-reactivity with H. capsulatum antigens, and antibody responses are difficult to detect in AIDS patients. 9.2. Antigen Detection The same cell wall and cytoplasmic components were also used as targets in antigen detection assays. Unfortunately, these assays were also limited because of significant cross-reactivity in sera from patients with other mycoses (i.e., aspergillosis and histo- plasmosis). To improve on this, a new target was sought, the 43-kDa glycoprotein (gp43) from culture filtrates; now believed to be a dominant antigen in this disease. An immunoblotting assay, performed on urine specimens, has demonstrated good sensitivity and excellent specificity for the detection of this antigen (43). An ELISA technique with a monoclonal antibody has successfully detected this antigen in serum, CSF, and BAL fluid of patients with confirmed acute and chronic disease states (44). Further, these antigen levels can be followed as a marker of treatment response (45). 9.3. Detection of Fungal Metabolites No tests of this nature are currently available. 9.4. Nucleic Acid Detection Despite some early studies using PCR on clinical specimens to detect sequences of the gene that codes for gp43 antigen, no tests of this nature are currently available (46). Conclusions and Recommendations Immunologic tests are useful for rapid diagnosis in suspected cases of paracoccid- ioidomycosis, as approximately 90% of patients with clinical disease have specific antibodies at the time of diagnosis. Further, in disseminated disease, antibody production is elevated and titers are high, providing useful prognostic information. Antibody testing is limited, though, as the presence of antibodies does not differentiate 4. Diagnostic Immunology 77 disease activity and their absence does not rule out disease, especially in patients with early disease or those who are severely immunocompromised. These are the popula- tions in whom antigenemia may be detectable, before the development of immune complexes. It is currently advisable to use more than one test for the diagnosis of paracoccidioidomycosis. Serum antibody and serum, urine, or site-specific antigen tests should both be ordered and any positive results should be monitored while the patient is on treatment. There is a concern that the assays may be detecting infection with other mycoses, so the results should be evaluated in the context of the entire clinical picture. 10. OTHER MYCOSES Immunodiagnostic tests have also been investigated for several other fungal infec- tions, namely mycetoma, zygomycosis (mucormycosis), penicilliosis, sporotrichosis, dermatophytoses, and pneumocystosis. While they target a variety of antigens, antibodies, and nucleic acids, they are unfortunately still limited by a lack of prospective trials and commercial availability and cannot yet be recommended for routine clinical use. REFERENCES 1. Horvath JA, Dummer S. The use of respiratory tract cultures in the diagnosis of invasive pulmonary aspergillosis. Am J Med 1996;100:171–178. 2. Obayashi T, Yoshida M, Mori T, et al. Plasma (1,3)-beta-d-glucan determination in the diagnosis of invasive deep mycosis and fungal febrile episodes. Lancet 1995;345:17–20. 3. Yuasa K, Goto H, Iguchi M, Okamura T, Ieki R. Evaluation of the diagnostic value of the measurement of (1,3)-beta-d-glucan in patients with pulmonary aspergillosis. Respiration 1996;63:78–83. 4. Ostrosky-Zeichner L, Alexander BD, Kett DH, et al. Multicenter clinical evaluation of the (1,3)-beta-d-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 2005;41:654–659. 5. Walsh TJ, Chanock SJ. Diagnosis of invasive fungal infections: advances in nonculture systems. Curr Clin Top Infect Dis 1998;18:101–153. 6. Mitsutake K, Miyazaki T, Tashiro T, et al. Enolase antigen, mannan antigen, Cand-Tec antigen, and beta-glucan in patients with candidemia. J Clin Microbiol 1996;34:1918–1921. 7. Sanchez ML, Pfaller MA, Cabezudo I, Bale M, Buschelman B. Diagnosis of dissemi- nated candidiasis in hospitalized patients using the Cand-Tec latex agglutination assay. Mycopathologia 1992;118:153–162. 8. Sendid B, Tabouret M, Poirot JL, Mathieu D, Fruit J, Poulain D. New enzyme immunoassays for sensitive detection of circulating Candida albicans mannan and antimannan antibodies: useful combined test for diagnosis of systemic candidiasis. 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Eur J Clin Microbiol Infect Dis 1996;15:139–145. 13. Wheat LJ. Rapid diagnosis of invasive aspergillosis by antigen detection. Transpl Infect Dis 2003;5:158–166. 14. Maertens J, Van Eldere J, Verhaegen J, Verbeken E, Verschakelen J, Boogaerts M. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. J Infect Dis 2002;186:1297–1306. 15. Pinel C, Fricker-Hidalgo H, Lebeau B, et al. Detection of circulating Aspergillus fumigatus galactomannan: value and limits of the Platelia test for diagnosing invasive aspergillosis. J Clin Microbiol 2003;41:2184–2186. 16. Fortun J, Martin-Davila P, Alvarez ME, et al. Aspergillus antigenemia sandwich-enzyme immunoassay test as a serodiagnostic method for invasive aspergillosis in liver transplant recipients. Transplantation 2001;71:145–149. 17. Yoo JH, Choi JH, Choi SM, et al. Application of nucleic acid sequence-based amplification for diagnosis of and monitoring the clinical course of invasive aspergillosis in patients with hematologic diseases. Clin Infect Dis 2005;40:392–398. 18. Tanner DC, Weinstein MP, Fedorciw B, Joho KL, Thorpe JJ, Reller L. Comparison of commercial kits for detection of cryptococcal antigen. J Clin Microbiol 1994;32:1680–1684. 19. Davies SF, Sarosi GA. Role of serodiagnostic tests and skin tests in the diagnosis of fungal disease. Clin Chest Med 1987;8:135–146. 20. Young EJ, Hirsh DD, Fainstein V, Williams TW. Pleural effusions due to Cryptococcus neoformans: a review of the literature and report of two cases with cryptococcal antigen determinations. Am Rev Respir Dis 1980;121:743–747. 21. Berlin L, Pincus JH. Cryptococcal meningitis: false-negative antigen test results and cultures in nonimmunosuppressed patients. Arch Neurol 1989;46:1312–1316. 22. Aberg JA, Mundy LM, Powderly WG. Pulmonary cryptococcosis in patients without HIV infection. Chest 1999;115:734–740. 23. Bialek R, Weiss M, Bekure-Nemariam K, et al. Detection of Cryptococcus neoformans DNA in tissue samples by nested and real-time PCR assays. Clin Diagn Lab Immunol 2002;9:461–469. 24. Rappelli P, Are R, Casu G, Fiori PL, Cappuccinelli P, Aceti A. Development of a nested PCR for detection of Cryptococcus neoformans in cerebrospinal fluid. J Clin Microbiol 1998;36:3438–3440. 25. Durkin MM, Connolly PA, Wheat LJ. Comparison of radioimmunoassay and enzyme-linked immunoassay methods for detection of Histoplasma capsulatum var. capsulatum antigen. J Clin Microbiol 1997;35:2252–2255. 26. Wheat LJ, Connolly-Stringfield P, Williams B et al. Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid. Am Rev Respir Dis 1992;145: 1421–1424. 27. Wheat LJ, Kohler RB, Tewari RP, Garten M, French ML. Significance of Histo- plasma antigen in the cerebrospinal fluid of patients with meningitis. Arch Intern Med 1989;149:302–304. 28. Williams B, Fojtasek M, Connolly-Stringfield P, Wheat J. Diagnosis of histoplasmosis by antigen detection during an outbreak in Indianapolis, Ind. Arch Pathol Lab Med 1994;118:1205–1208. 4. Diagnostic Immunology 79 29. Wheat J, French ML, Kohler RB, et al. The diagnostic laboratory tests for histoplasmosis. Ann Intern Med 1982;97:680–685. 30. Wheat LJ. Current diagnosis of histoplasmosis. Trends Microbiol 2003;11:488–494. 31. Klein BS, Vergeront JM, Kaufman L, et al. Serological tests for blastomycosis: assessments during a large point-source outbreak in Wisconsin. J Infect Dis 1987;155:262–268. 32. Soufleris AJ, Klein BS, Courtney BT, Proctor ME, Jones JM. Utility of anti-WI-1 serological testing in the diagnosis of blastomycosis in Wisconsin residents. Clin Infect Dis 1994; 19:87–92. 33. Durkin M, Witt J, LeMonte A, Wheat B, Connolly P. Antigen assay with the potential to aid in diagnosis of blastomycosis. J Clin Microbiol 2004;42:4873–4875. 34. Bouza E, Dreyer JS, Hewitt WL, Meyer RD. Coccidioidal meningitis: an analysis of thirty- one cases and review of the literature. Medicine 1981;60:139–172. 35. Antoniskis D, Larsen RA, Akil B, Rarick MU, Leedom JM. Seronegative disseminated coccidioidomycosis in patients with HIV infection. AIDS 1990;4:691–693. 36. Pappagianis D, Krasnow

RI, Beall S. False-positive reactions of cerebrospinal fluid and diluted sera with the coccidioidal latex-agglutination test. Am J Clin Pathol 1976;66: 916–921. 37. Smith CE, Saito MT, Beard RR, Kepp RM, Clark RW, Eddie BU. Serological tests in the diagnosis and prognosis of coccidioidomycosis. Am J Hyg 1950;52:1–21. 38. Bronnimann DA, Adam RD, Galgiani JN, et al. Coccidioidomycosis in the acquired immun- odeficiency syndrome. Ann Intern Med 1987;106:372–379. 39. Cohen IM, Galgiani JN, Potter D, Ogden DA. Coccidioidomycosis in renal replacement therapy. Arch Intern Med 1982;142:489–494. 40. Kaufman L, Sekhon AS, Moledina N, Jalbert M, Pappagianis D. Comparative evaluation of commercial Premier EIA and microimmunodiffusion and complement fixation tests for Coccidioides immitis antibodies. J Clin Microbiol 1995;33:618–619. 41. Galgiani JN, Grace GM, Lundergen LL. New serologic tests for early detection of coccid- ioidomycosis. J Infect Dis 1991;163:671–674. 42. Johnson SM, Simmons KA, Pappagianis D. Amplification of coccidioidal DNA in clinical specimens by PCR. J Clin Microbiol 2004;42:1982–1985. 43. Salina MA, Shikanai-Yasuda MA, Mendes RP, Barraviera B, Mendes-Giannini MJ. Detection of circulating Paracoccidioides brasiliensis antigen in urine of paracoc- cidioidomycosis patients before and during treatment. J Clin Microbiol 1998;36: 1723–1728. 44. Marques da Silva SH, Colombo AL, Blotta MH, Lopes JD, Queiroz-Telles F, Pires de Camargo Z. Detection of circulating gp43 antigen in serum, cerebrospinal fluid and bronchoalveolar lavage of patients with paracoccidioidomycosis. J Clin Microbiol 2003;41:3675–3680. 45. Marques da Silva SH, Queiroz-Telles F, Colombo AL, Blotta MH, Lopes JD, Pires De Camargo Z. Monitoring gp43 antigenemia in paracoccidioidomycosis patients during therapy. J Clin Microbiol 2004;42:2419–2424. 46. Bialek R, Ibricevic A, Aepinus C, et al. Detection of Paracoccidioides brasiliensis in tissue samples by a nested PCR assay. J Clin Microbiol 2000;38:2940–2942. SUGGESTED READINGS Galgiani J. Laboratory diagnosis of coccidioidomycosis. UpToDate; www.uptodate.com. Pappagianis D, Zimmer BL. Serology of coccidioidomycosis. Clin Microbiol Rev 1990;3: 247–268. 80 Samit S. Desai and Brian Wong Powderly WG, Cloud GA, Dismukes WE, Saag MS. Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis. Clin Infect Dis 1994;18:789–792. Wheat LJ. Rapid diagnosis of invasive aspergillosis by antigen detection. Transpl Infect Dis 2003;5:158–166. Yeo SF, Wong B. Current status of nonculture methods for diagnosis of invasive fungal infections. Clin Microbiol Rev 2002;15:465–484. 5 Diagnostic Radiology Maria Angela C. Hospenthal, MD and Constanza J. Gutierrez, MD 1. INTRODUCTION Although there are no pathognomonic radiological findings associated with human mycoses, use of diagnostic imaging is integral to the diagnosis and management of most fungal infections. In conjunction with clinical data, including patient symptoms, duration of illness, underlying immune function, and other risk factors (including endemic exposures, invasive devices, coexisting disease, surgeries, and other therapies), radiographic diagnosis can be directed to enhance its sensitivity and thus usefulness. In human fungal infections, imaging of the central nervous system (CNS), upper and lower respiratory tract, abdomen, and musculoskeletal system is generally the focus of these diagnostic studies. 2. CENTRAL NERVOUS SYSTEM IMAGING Magnetic resonance imaging (MRI) is superior to computed tomography (CT) in evaluating fungal infections of the brain and has been shown to be more sensitive than CT for detecting abnormalities. MRI is especially helpful in the early phases of disease when the brain CT may be nondiagnostic. MRI takes advantage of the inherent properties of molecules, especially hydrogen, and manipulates their behavior in an electromagnetic field to generate an image. The composition of tissues and their differences when pathology is present can therefore be distinguished by altering parameters of the electromagnetic field to see the effect on the molecules of the tissue being evaluated. Terminology to include longitudinal relaxation time (T1) and transverse relaxation time (T2) relate to signal intensities that offer details on specific tissue characteristics. Findings on MRI, such as edema and contrast enhancement, are affected by the inflammatory response, which itself is highly dependent on the competence of the immune system. Nevertheless, noncircumscribed, ill-defined areas with little or no contrast enhancement should raise the suspicion for fungal infection (1). CT of the brain with contrast may be normal initially and thus is more helpful From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 81 82 Maria Angela C. Hospenthal and Constanza J. Gutierrez in assessing later stages of infection with eventual findings of focal ring enhancing or hemorrhagic lesions. Other brain imaging modalities include proton magnetic resonance spectroscopy with MRI, which has been reported to be useful in the evaluation of infection due to zygomycosis (mucormycosis) and cryptococcosis (2). A wide variety of radiologic findings can be found, although intracerebral masses and meningeal enhancement predominate in these infections (Table 5.1). 2.1. CNS Mass Lesions Intracerebral masses are one of the more common findings in fungal brain infections. Predominantly, granulomas or solid enhancing lesions are reported. In Aspergillus infections, these have sometimes been referred to as “aspergillomas.” Likewise, in patients with cryptococcal infections, the term “cryptococcoma” has been used. Most of these lesions are found in the basal ganglia. On T2 weighted images (T2WI), cryptococcomas can be single or multiple punctate hyperintense round lesions usually less than 3 mm in size (3,4). Intraparenchymal cryptococcomas show low signal intensity on T1 weighted images (T1W1) and high intensity on T2 WI (5,6). Persis- tence of cryptococcomas over a prolonged period of time has been documented and found to be inconsistent with active disease (7). Single or multiple enhancing brain lesions have also been reported in Histoplasma, Candida, and Paracoccidioides infections. Abscesses are frequently found in fungal brain infections (8). These lesions can be multiple, hypodense, and may exert little mass effect. They may or may not enhance (9) (Fig. 5.1). Although abscesses occur most commonly in the cerebral hemispheres, they have also been visualized in the cerebellum and brainstem (10). Organisms reported to cause abscess formation include Aspergillus, Coccidioides, Cryptococcus, and Candida. Candidal organisms tend to cause focal necrosis producing microabscesses (11,12). Table 5.1 Abnormalities more commonly seen in central nervous system imaging of fungal infections Radiological finding Fungus Granulomas or solid enhancing lesions Aspergillus, Cryptococcus, Histoplasma, Candida, Paracoccidioides Abscesses Aspergillus, Blastomyces (epidural), Coccidioides, Cryptococcus, Candida, dematiaceous fungi, Pseudallescheria boydii (Scedosporium apiospermum) Parenchymal/leptomeningeal Cryptococcus nodules; pseudocysts Hemorrhagic/infarcted lesions Aspergillus Meningeal enhancement Blastomyces, Coccidioides (chronic granulomatous), Cryptococcus, Histoplasma, Paracoccidioides, Aspergillus Hydrocephalus Cryptococcus, Coccidioides, Paracoccidioides 5. Diagnostic Radiology 83 Fig. 5.1. Contrast-enhanced MRI showing multiple ring-enhancing brain abscesses in immunocompromised patient with disseminated aspergillosis. Note the lack of surrounding edema. (Courtesy of Dr. D. R. Hospenthal.). Less commonly, the dematiaceous moulds and Pseudallescheria boydii have been reported to cause one or multiple brain abscesses (13). CNS abscesses outside the brain parenchyma are not common, although Blastomyces has been reported to cause epidural abscesses (14). Other intracerebral masses associated with fungal pathogens include edematous, hemorrhagic, or infarcted lesions such as those seen in Aspergillus infections (9). The hemorrhagic lesion, usually a consequence of an area of infarction, is an early radiologic sign owing to the angioinvasive nature of certain fungi (8,15). A peripheral 84 Maria Angela C. Hospenthal and Constanza J. Gutierrez ring of low signal intensity relates to a dense population of hyphal elements and small areas of hemorrhage (16). On cross-sectional imaging, these lesions show little or no enhancement or mass effect (9). Less frequently seen intracerebral lesions include parenchymal or leptomeningeal nodules, and non-enhancing, gelatinous pseudocysts and dilated Virchow-Robin (perivascular) spaces, found mainly in cryptococcal infec- tions (5,17) (Fig. 5.2). 2.2. Meningeal Enhancement Diffuse enhancement of the meninges on MRI is another common radiological finding of fungal infection of the CNS, thought to be due to active inflammation (meningitis). Histoplasma, Blastomyces, Coccidioides, Paracoccidioides, Cryptococcus, as well as Aspergillus have all been observed to produce meningeal enhancement. Coccidioides Fig. 5.2. Contrast-enhanced TI transaxial MRI image of the brain demonstrating low signal intensity lesions in the bilateral basal ganglia (left greater than right) associated with no significant enhancement, consistent with gelatinous pseudocysts of cryptococcosis. Also note mild meningeal enhancement. 5. Diagnostic Radiology 85 Fig. 5.3. MRI of brain revealing leptomeningeal enhancement and hydrocephalus in a patient with coccidioidomycosis. meningitis early in its course can cause focal or nodular enhancement in the basal cisterns which represents focal organization of the fungus surrounded by inflammation (18). 2.3. Hydrocephalus Hydrocephalus, a consequence of meningeal involvement, is an additional finding associated with infections by Cryptococcus, Coccidioides, and Paracoccidioides (19) (Fig. 5.3). Although CT is helpful in identifying dilated ventricles, MRI appears better in determining the patency of the aqueduct of Sylvius. Other nonspecific CNS radiological findings include early vascular enhancement and diffuse cerebral edema. 3. RESPIRATORY TRACT IMAGING 3.1. Sinus Imaging CT imaging is a useful initial test to evaluate the extent of fungal sinus disease. The CT scan defines soft tissue invasion, necrosis, early bone erosion, and cavernous sinus thrombosis (20). When findings are suggestive of fungal sinusitis but the diagnosis is 86 Maria Angela C. Hospenthal and Constanza J. Gutierrez uncertain, MRI with or without gadolinium is the best radiological means to further evaluate the disease (21). Central areas of hyperattenuation on CT correspond to hypointense signals on T1WI and signal void with T2WI MRI. Early changes in major vessels and intracranial extension are also best seen on MRI, as is possible cavernous sinus thrombosis and embolic phenomena. It is thought that fungal sinusitis also has characteristic high signal intensity on T1WI and very low signal intensity on T2WI. The paranasal sinuses are the most frequently affected, with the maxillary and ethmoid sinuses being the most commonly involved, followed by the sphenoid sinuses. Bilateral involvement is slightly more common than unilateral involvement (22). Radiologic findings include opacification of multiple paranasal sinuses, with possible demonstration of sinus cavity expansion and erosion of the involved sinus wall. Bone destruction, erosion, and osteomyelitis have been reported in both the invasive and allergic form of Aspergillus sinusitis, as well as in infections due to zygomycetes (21,23) (Fig. 5.4). A soft tissue mass or a sinus “aspergilloma” is reported as a major CT finding of the invasive granulomatous form of fungal sinusitis from Aspergillus. It can appear as sinus opacification associated with flocculent calcifications (24) (Fig. 5.5). The mass may either present as a homogenous density or have components of lower attenuation. Intraorbital and/or intracranial extension may occasionally occur. Air-fluid levels may be found though these are rare in either the invasive or noninvasive forms of fungal sinusitis (20). Other findings include scattered intrasinus high attenuation areas amid mucosal thickening on unenhanced CT scans. Fig. 5.4. Transaxial sinus CT of patient with zygomycosis demonstrating osteolysis of the hard palate (arrow) and left maxillary sinus mucosal thickening with surrounding soft tissue air. 5. Diagnostic Radiology 87 Fig. 5.5. Transaxial CT image through the sinuses demonstrating high-density opacification of the maxillary sinuses consistent with fungal sinusitis. 3.2. Pulmonary Imaging Definitive diagnosis of a pulmonary fungal infection by radiological imaging alone is not possible as other infectious organisms, and likewise, noninfectious pulmonary syndromes, can mimic radiological findings (25). The most useful tools to assess lung infections include chest roentgenography and CT (26). Chest radiography in the earlier stages of fungal disease may be normal; thus CT is the superior imaging modality as it has been shown to reveal abnormalities much earlier than chest x-ray films. MRI, although reported to have been useful in the work-up for Pneumocystis disease, has not been recognized as a significant diagnostic tool for the majority of pulmonary fungal infections. Fungal infection of the lung presents generally with a wide variety of nonspecific radiographic patterns (Table 5.2). 3.2.1. Airspace and Interstitial Opacities Nonspecific airspace opacities are the most frequent radiologic findings found with any pulmonary infectious process. Alveolar, “patchy,” “air-space,” or “mass-like” opacities have been identified in many fungal diseases, often progressing to areas of consolidation in the lung. Alveolar opacities have been noted in both endemic 88 Maria Angela C. Hospenthal and Constanza J. Gutierrez Table 5.2 Abnormalities more commonly seen in pulmonary imaging of fungal infections Radiological finding Fungus Alveolar infiltrates Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcus, Histoplasma, Pneumocystis, zygomycetes Interstitial infiltrates Aspergillus, Coccidioides, Cryptococcus, Histoplasma, Paracoccidioides, Penicillium, Pneumocystis Nodules Aspergillus/zygomycetes (halo sign), Candida, Coccidioides, Cryptococcus, Histoplasma, Paracoccidioides, Pneumocystis Masses Aspergillus, Blastomyces, Coccidioides, Cryptococcus, zygomycetes Cavitation Aspergillus/Zygomycetes (air crescent sign), Blastomyces, Coccidioides, Cryptococcus, Histoplasma, Paracoccidioides, Pneumocystis Abscesses Candida, Pseudallescheria (Scedosporium), zygomycetes Adenopathy Coccidioides, Cryptococcus, Histoplasma Pleural effusion Candida, Coccidioides, Cryptococcus, Histoplasma, Pneumocystis and opportunistic

fungal infections. Airspace opacities have been noted as a frequent initial pattern in invasive pulmonary aspergillosis (IPA). Opacities may be unifocal or multifocal and then progress to diffuse consolidation, although segmental areas of consolidation has been noted as one of the most common CT patterns in IPA (27,28) (Fig. 5.6). Other disease processes resulting from Aspergillus infection such as bronchopneumonia, hypersensitivity pneumonitis, chronic necrotizing aspergillosis, and semi-invasive aspergillosis have also presented with alveolar opacities, often progressing to consolidation (26,27,29). Interstitial, “reticular,” “reticulonodular,” and “linear” opacities have also been observed in many fungal infections. Diffuse bilateral interstitial opacities in a perihilar distribution (25,30,31) is the most common pattern seen in Pneumocystis infection (Fig. 5.7). Chest CT often reveals perihilar ground glass opacity in a mosaic pattern with patchy distribution of affected lung interspersed with areas of normal lung, and noted thickening of the interlobular septa (26). Interstitial opacities are also the most common pattern seen in cryptococcosis (32). Ground-glass attenuation may be seen in acquired immunodeficiency syndrome (AIDS) patients with this infection. Aspergillus can affect the lung in a variety of ways, most of which can present in an interstitial pattern. These range from nodular opacities of invasive and semi-invasive disease, mimicking the radiologic findings of reactivation tuberculosis (TB), to coarse reticulation found in chronic hypersensitivity pneumonitis (26,27). A miliary or reticulonodular pattern is commonly seen in Blastomyces infection. Coccidioides pneumonia has been noted with diffuse reticulonodular lesions, especially in the 5. Diagnostic Radiology 89 Fig. 5.6. Transaxial CT image through the chest of patient with invasive pulmonary aspergillosis demonstrating diffuse ground-glass opacity and bibasilar consolidation. (Courtesy of Dr. D. R. Hospenthal.). setting of AIDS. Heavy exposure to Histoplasma can similarly present with diffuse reticulonodular opacities, such as those occurring in acute disseminated disease (33). Other organisms commonly demonstrating interstitial opacities include Penicillium marneffei in the setting of human immunodeficiency virus (HIV) infection and paracoccidioidomycosis. In Paracoccidioides infection, the “reversed halo sign” of ground-glass opacity, surrounded by denser air space consolidation of crescent and ring shapes, has been reported in 10% of patients (34). Distribution and location of opacities are also nonspecific. Opacities may be confined to a lobe or they may be diffuse as seen in disseminated disease. Hematogenous candidal spread can manifest as perivascular pulmonary opacities [35]. Pneumocystis infection is observed with bilateral hilar opacities with a peripheral spread. For persons on prophylactic aerosolized pentamidine, the infection may present as an upper lobe infiltrative process suggestive of TB. Allergic bronchopulmonary aspergillosis often presents with fleeting or migratory upper lobe opacities (27). Phantom opacities that resolve in one segment and then reappear in another lung field have also been seen in coccidioidomycosis (35). The shape of infiltrates can sometimes aid in the diagnosis. Wedge-shaped opacities, reflecting invasion of blood vessels with subsequent lung infarction, are suggestive of invasive Aspergillus or zygomycetes (36). Uncommon pathogens that can cause infections presenting with nonspecific pulmonary opacities include Fusarium, Trichosporon, Malassezia furfur, and the phaeohyphomycetes (37). 90 Maria Angela C. Hospenthal and Constanza J. Gutierrez Fig. 5.7. Chest radiograph showing interstitial prominence and ground-glass opacity in a patient with Pneumocystis pneumonia. 3.2.2. Nodules A well defined nodule, either single or multiple, has been reported as a frequent initial radiographic pattern of IPA (38). This nodular lesion may be surrounded by a rim of hemorrhage from thrombosis of fungi within pulmonary vessels (39). Days to weeks after treatment of neutropenia, patients infected with Aspergillus may present with ground-glass attenuation around the nodules recognized as the “halo sign” (27,40,41) (Fig. 5.8). The “halo sign” is highly suggestive of angioinvasive aspergillosis, but is nonspecific. It is thought that the surrounding ground-glass opacity may be related to hemorrhage from the vascular involvement. Other infectious processes including the zygomycosis, Candida, herpes simplex virus, and cytomegalovirus infections, as well as noninfectious processes such as Wegener’s granulomatosis, Kaposi’s sarcoma, and hemorrhagic metastatic malignancies, have also presented with halo signs (42,43). Nodular lesions may also be observed with branching linear opacities recognized 5. Diagnostic Radiology 91 Fig. 5.8. Transaxial CT image of the chest with a right middle lobe nodule with surrounding ground glass opacity (halo sign). This is consistent with invasive aspergillosis in an immuno- compromised patient. as the “tree in bud” pattern seen in Aspergillus bronchiolitis (26). A tree in bud pattern suggests a small airways process, a disease process that may be spread endobronchially. Similar lesions are found in endobronchial spread of mycobacterial, viral, and mycoplasma pneumonia. Nodules from zygomycetes can be indistinguishable from IPA. The most common finding in pulmonary cryptococcosis are nodules, solitary or multiple, with or without cavitation, ranging from 5 mm to 20 mm in size with smooth or irregular margins, associated with other parenchymal findings such as masses and consolidation (44–46). Miliary nodules are less commonly found in AIDS patients with cryptococcosis (47). Other organisms that can present with diffuse nonspecific nodular lesions include disseminated Candida and Histoplasma. Nodules can turn to “buck shot” calcifications in pulmonary histoplasmosis (36). Approximately 5% of persons who develop Coccidioides pneumonia may develop solitary pulmonary nodules. Infections with Pneumocystis, Scedosporium, and Paracoccidioides have also demonstrated pulmonary nodules. 3.2.3. Masses Parenchymal masses may include aspergillomas, 3 to 5 cm mobile, round or oval masses, usually solitary, and seen in the upper lobe within a preexisting cavity (Fig. 5.9). These masses may be partially surrounded by a radiolucent crescent (Monod’s sign) of 92 Maria Angela C. Hospenthal and Constanza J. Gutierrez Fig. 5.9. Transaxial CT image of the chest showing bilateral upper lobe bronchiectasis, right pleural thickening, and right upper lobe ground-glass opacity and aspergilloma (soft tissue mass in preexisting cavity). varying thickness (27,48). Occasionally, coccidioidal infections may leave persistent lesions on chest x-ray exam, most commonly in the peripheral cavity (35). The occasional “fungus ball” can form inside the cavity, rupture into the pleural space, and produce an air-fluid level on an upright chest x-ray study. Nonspecific mass lesions have been reported in infections with Cryptococcus, Pneumocystis, and the zygomycetes. Nonparenchymal masses may be seen in the hilar or mediastinal areas. Chronic pulmonary blastomycosis might present with a single large perihilar mass that often warrants a thoracotomy to rule out possible carcinoma. Other findings of cryptococcosis in AIDS patients include mediastinal masses. 3.2.4. Cavitation Virtually any nodular lesion has the potential to cavitate. Nodular lesions seen in Aspergillus and zygomycetes infections may progress to cavitate to what is recognized as the “air crescent sign” (27,41,42,49). The air crescent sign represents cavitation of nodules caused by resorption of necrotic tissue by returning neutrophils (39) (Fig. 5.10). It is usually unilateral and frequently in the upper lobes (26). Other nodules, single or multiple, can cavitate and then proceed to either diffuse pulmonary consolidation or abrupt development of large wedge-shaped pleural based lesions mimicking bland infarction. Thin- or thick-walled cavities as well as cavitary infiltrates can appear in subacute invasive aspergillosis and chronic progressive coccidioidomycosis, both of 5. Diagnostic Radiology 93 Fig. 5.10. Transaxial CT scan of the chest demonstrates a cavity in the left upper lobe with dependent soft tissue in a patient with invasive aspergillosis (air crescent sign). (Courtesy of Dr. D. R. Hospenthal.). which can mimic TB (36). Approximately 5% of persons who develop Coccidioides pneumonia develop thin-walled solitary cavities, typically near the pleura (Fig. 5.11). A chronic form of Coccidioides pneumonia presents as a slowly progressive fibro- cavitary process of biapical fibronodular lesions with retraction and cavitation. In pulmonary histoplasmosis, upper lobe cavities are common, except in persons with HIV infection. Cavitary infiltrates have also been demonstrated in disseminated disease. Fibrotic apical infiltrates with cavitation have been reported in chronic pulmonary histoplasmosis which can be confused with TB infection or coinfection on chest x-ray examination (36). Other fungal infections reported to cause cavitary disease include sporotrichosis and paracoccidioidomycosis; nodular areas are sometimes confluent, often in the lower lobes; cavitation occurs in one-third of cases. Cavitation from blasto- mycosis is unusual and not as commonly seen as in mycobacterial or Histoplasma infections. Cryptococcal infection may present with cavitary masses or nodules, though this is uncommonly seen in the setting of AIDS infection. In cancer patients infected with Pneumocystis previously given prophylactic aerosolized pentamidine, upper lobe infiltrative disease suggestive of tuberculosis may be seen, but cavitary lesions are very uncommon. 3.2.5. Adenopathy Adenopathy has been observed commonly in histoplasmosis, coccidioidomycosis, and cryptococcosis. In acute histoplasmosis, a common finding in a low-level exposure includes enlarged hilar or mediastinal lymphadenopathy. In heavy exposure, 94 Maria Angela C. Hospenthal and Constanza J. Gutierrez Fig. 5.11. Transaxial CT scan through the chest and chest radiograph demonstrating a thin-walled cavity in the left upper lobe in an asymptomatic patient proven to have coccid- ioidomycosis. (Courtesy of Dr. D. R. Hospenthal.). the mediastinal adenopathy is usually accompanied by diffuse reticulonodular infil- trates as mentioned previously. Lymph nodes can potentially calcify. Occasionally, these lymph nodes coalesce and form granulomas which may rupture and result in chronic inflammation with subsequent fibrosis (50). This process, known as fibrosing mediastinitis, can partially obstruct airways, vessels, and the esophagus. Mediastinal lymphadenopathy is uncommon in disseminated histoplasmosis, occurring at less than 10% in one series. Coccidioidomycosis is also noted to present with bilateral hilar adenopathy. Prominent hilar adenopathy is occasionally seen in cryptococcosis. Radiologic findings vary widely in Pneumocystis infections but lymphadenopathy is extremely rare. 3.2.6. Pleural Abnormalities The effect of fungal infections on the pleura and pleural cavity is not as common as the other previously described radiologic findings. Pleural thickening with concomitant upper lobe consolidation potentially progressing to cavitation over weeks to months can be seen in semi-invasive pulmonary aspergillosis (27). Pleural effusions have been noted in candidal pneumonia. Large parapneumonic effusions have been documented in coccidioidomycosis. Other organisms that have demonstrated pleural effusions include Cryptococcus, Histoplasma, and Scedosporium. Effusions are unusual in Blastomyces and Pneumocystis infections. 3.2.7. Airway Abnormalities Tracheal or bronchial wall mucosal thickening along with airway plaques can be seen in invasive aspergillosis (26,27). Cryptococcus infection of the larynx can present on CT soft tissue images of the neck as vocal cord irregularities and asymmetric enlargement (51). Cylindric bronchiectasis in a central distribution, as well as traction 5. Diagnostic Radiology 95 bronchiectasis, have also been noted on CT images of various forms of Aspergillus as well as Paracoccidioides infections (27,52). 3.2.8. Miscellaneous Hematogenous spread of Candida can cause multiple abscesses in the body, including the lungs (53). Zygomycosis and pseudallescheriasis have also been reported to cause pulmonary abscesses (54,55). Atelectasis, which may appear as bilateral lower lobe consolidation, has been noted in various pathologic processes caused by Aspergillus (27). Thin-walled cysts or pneumatoceles can form in Pneumocystis infec- tions, especially in patients receiving prophylaxis with aerosolized pentamidine and trimethoprim/sulfamethoxazole (TMP/SMX) (30). These upper lobe lesions increase the risk of developing pneumothoraces. End-stage honeycombing can be seen in the chronic form of hypersensitivity pneumonitis secondary to Aspergillus (27). Pseudoa- neurysm of the aortic arch has been noted in IPA (56). A new imaging modality has recently been used to study invasive aspergillosis. Multidetector CT (MDCT) angiography takes advantage of the angioinvasive nature of Aspergillus and allows direct detection of vessel occlusion up to a peripheral lesion, with high-resolution images demonstrating possibly the earliest sign of disease from Aspergillus (57). 4. ABDOMINAL IMAGING CT or MRI should be the initial imaging modality used to evaluate the abdomen for signs of fungal infection. Ultrasonography, a safer, low-cost method, may then be obtained to follow up noted disease processes. Serial ultrasounds every 3 to 4 weeks may be used to monitor response to therapy, typically observed as decreasing size and number of lesions, or may be useful in detecting evolution of new lesions (58). Once the ultrasound is clear, a repeat CT or MRI is suggested. Similar to other affected organs mentioned in the preceding text, radiologic findings of abdominal fungal infections are varied to include nonspecific lesions, organomegaly, and lymphadenopathy. 4.1. Target Lesions Candida is one of the main fungi to cause abdominal disease. Involvement of the liver, biliary tree, pancreas, and spleen has been documented in disseminated disease (59). Target lesions seen in the spleen and liver resulting from candidal infection are most commonly detected on CT or MRI after the resolution of neutropenic episodes (58) (Fig. 5.12). On abdominal CT, chronic disseminated (formerly hepatosplenic) candidiasis is characterized by small, round, low-attenuation lesions scattered through the liver

and spleen with occasional peripheral enhancement (60). Occasionally, multiple small low attenuation lesions in the spleen and kidneys are seen without lymph node enlargement or hepatosplenomegaly (61). Four dominant findings on ultra- sound have been described. Most commonly, uniform hypoechoic lesions are noted and can be seen in conjunction with the other three patterns. A “wheel within a wheel” pattern can be seen representing an outer hypoechoic area of fibrosis surrounding a hyperechoic area of inflammation. A “bull’s eye” measuring from 1 to 4 cm may 96 Maria Angela C. Hospenthal and Constanza J. Gutierrez Fig. 5.12. Contrast-enhanced CT scan through the abdomen showing multiple subcen- timeter low attenuation hepatic and splenic lesions in patient with chronic disseminated candidiasis. (Courtesy of Dr. D. R. Hospenthal.). evolve from primary lesions. “Echogenic foci,” usually seen late, correlate with central fibrosis, calcifications, or both (62). MRI has been reported to be superior to CT in characterizing chronic disseminated candidiasis. Coccidioides infections have also been reported to present with splenic lesions with central areas of low attenuation on CT imaging (61). 4.2. Organomegaly Moderate to marked enlargement of the liver, spleen, and adrenals have been noted in disseminated histoplasmosis (61,63). Cryptococcal infections have also been reported to produce marked splenomegaly and mild hepatomegaly (61). 4.3. Lymphadenopathy Enlarged lymph nodes with or without central or diffuse low attenuation are seen in the majority of patients with abdominal histoplasmosis (61). On CT imaging, enlarged lymph nodes have also been noted in the case of cryptococcal infection. 4.4. Miscellaneous Abdominal abscesses have been reported in deeply invasive candidiasis (59). Uncommon findings in disseminated histoplasmosis include colonic wall thickening, and omental and mesenteric infiltration (61). Adrenal masses, vascular occlusion, and 5. Diagnostic Radiology 97 extensive necrosis have also been noted. Multiple scattered low-attenuation foci can persist from focal scarring and granulomatous change, which may eventually result in calcifications. 5. MUSCULOSKELETAL IMAGING Bone scans are the imaging modality of choice in assessing fungal infections of the skeletal system (Fig. 5.13). Technetium uptake is dependent on blood flow, while gallium uptake is dependent on the presence of leukocytes in the area of inflammation (64). Although positive bone scans may be seen as early as 24 hours after the onset of infection, a normal scan may be the result of scanning before the onset of reactive hyperperfusion. Osteomyelitis is the most frequent radiologic finding associated with skeletal fungal infections, although radiographic appearance is nonspecific and indis- tinguishable among fungi or from bacterial or neoplastic disease. Bone MRI may be sensitive for picking up early lesions of osteomyelitis. 5.1. Osteomyelitis In blastomycosis, the vertebral column is infrequently involved. The skull, ribs, and the epiphyseal ends of long bones are more commonly affected (65). In the tubular Fig. 5.13. Bone scan demonstrates increased uptake at approximately T8, T11, and T12. Although this patient had coccidioidomycosis, these findings are nonspecific and could represent another infection or inflammatory or neoplastic process. 98 Maria Angela C. Hospenthal and Constanza J. Gutierrez Fig. 5.14. Plain radiograph of the right ankle showing a lytic lesion in the medial aspect of the distal tibia secondary to coccidioidomycosis. bones of the extremities, eccentric saucer-shaped erosions may be seen beneath a cutaneous abscess. Epiphyseal or metaphyseal focal or diffuse osteomyelitis has been reported as well as cystic foci or diffuse “moth-eaten” areas in the carpal or tarsal areas (66). Histoplasmosis similarly affects the pelvis, skull, ribs, and small tubular bones. 5. Diagnostic Radiology 99 Radiologically, osteoporosis, joint space narrowing, and bony erosion may be seen similar to tuberculosis. Candida osteomyelitis usually occurs in the setting of disseminated candidiasis, affecting primarily the axial spine of adults and the long bones of children (66). Soft tissue swelling, joint space narrowing, and irregularities of subchondral bone are noted (67). Coccidioidomycosis also primarily affects the vertebral column and ribs. There is a tendency to involve multiple segments of the vertebrae, sometimes with “skip lesions” (65). Radiographs reveal periostitis as well as multiple well-demarcated lytic foci in the metaphyses of long tubular bones and in bony prominences. In the spine, one or more vertebral bodies may be involved, typically with paraspinal masses and contiguous rib lesions (67) (Fig. 5.14). Crypto- coccosis presents with nonspecific radiographic features to include osteolytic lesions with discrete margins, mild or absent surrounding sclerosis, and little or no periosteal reaction. Zygomycosis generally causes osteolytic changes to the skull or face (67). With Madura foot (eumycotic mycetoma), a chronic granulomatous disease of the subcutaneous tissues and bone, standard x-ray films may reveal abnormalities, though CT has been reported to be more sensitive in the earlier stages of the disease. Typically, single or multiple bony defects with extensive soft tissue and bony disruption occurring with sclerosis and periostitis are seen (67). Other organisms reported to cause radio- logic abnormalities of soft tissue and bone include Scedosporium, Paecilomyces, Pseudallescheria boydii, and Sporothrix schenckii (13,55,67). Osseous and disk space destruction and a paraspinal mass resembling those of TB have been reported in aspergillosis (67). REFERENCES 1. 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Disseminated histoplasmosis: abdominal CT findings in 16 patients. AJR Am J Roentgenol 1991;157:955–958. 64. Bonakdar-pour A, Gaines VD. The radiology of osteomyelitis. Orthop Clin North Am 1983;14:21–37. 65. Sapico FL, Montogmerie JZ. Vertebral osteomyelitis. Infect Dis Clin North Am 1990;4:539–550. 66. Katzenstein D. Isolated Candida arthritis. Report of a case and definition of a distinct clinical syndrome. Arthritis Rheum 1985;28:1421–1424. 67. Chhem RK, Wang S, Jaovisidha S, et al. Imaging of fungal, viral, and parasitic muscu- loskeletal and spinal diseases. Radiol Clin North Am 2001;39:357–378. SUGGESTED READINGS Davies SF. An overview of pulmonary fungal infections. Clin Chest Med 1987;8:495–512. DeLone DR, Goldstein RA, Petermann G, et al. Disseminated aspergillosis involving the brain: distribution and imaging characteristics. AJNR Am J Neuroradiol 1999;20:1597–1604. Franquet T, Gimenez A, Hidalgo A. Imaging of opportunistic fungal infections in the immuno- compromised patient. Eur J Radiol 2004;51:130–138. Gotway MB, Dawn SK, Caoili EM, Reddy GP, Araoz PA, Webb WR. The radiologic spectrum of pulmonary Aspergillus infections. J Comput Assist Tomogr 2002;26:159–173. Manning SC, Merkel M, Kriesel K, Vuitch F, Marple B. Computed tomography and magnetic resonance diagnosis of allergic fungal sinusitis. Laryngoscope 1997;107:170–176. Radin R. HIV infection: analysis in 259 consecutive patients with abnormal abdominal CT findings. Radiol 1995;197:712–722. Som PM. Imaging of paranasal sinus fungal disease. Otolaryngol Clin North Am 1993;26: 983–994. III Antifungal Agents 6 Antifungal Agents Russell E. Lewis, PharmD and Annette W. Fothergill, MA, MBA 1. INTRODUCTION Until the 1950s, relatively few drugs were available for the treatment of superficial or invasive mycoses. The era of antifungal chemotherapy effectively began in 1955, with the discovery of the polyene antifungals nystatin and amphotericin B, followed closely by the discovery of the first topical azole antifungal agent, chlormidazole, in 1958 (Fig. 6.1). Although amphotericin B was to remain the mainstay of therapy for serious fungal infections for more than 40 years, infusion-related side effects and dose-limiting nephrotoxicity associated with its use prompted continued the search for equally effective but less toxic alternatives. In the 1960s, a synthetic fluorinated pyrim- idine analogue originally developed as an antineoplastic agent, flucytosine, was found to have potent antifungal activity against common yeasts. Unfortunately, resistance to flucytosine developed rapidly when the drug was administered as monotherapy, thus restricting its use to combination therapy with amphotericin B. The next major milestone in antifungal therapy was not realized until 1981, when the first orally bioavailable systemic azole, ketoconazole, was introduced into clinical practice. For almost a decade, it would be regarded as the drug of choice for chronic mucocutaneous candidiasis, mild to moderate blastomycosis, histoplasmosis, paracoccidioidomycosis and coccidioidomycosis, and occasionally deep-seated Candida and Cryptococcus infections in patients who could not tolerate amphotericin B (1). Because ketoconazole is a highly lipophilic weak base, it has many undesirable physiochemical characteristics that increased its toxicity and limited its usefulness in critically ill patients including: • Limited absorption of the drug at elevated gastric pH • Lack of an intravenous formulation • Requirement for extensive cytochrome P450 biotransformation before elimination, resulting in a high propensity for drug–drug interactions • Dose-related gastrointestinal, hepatic, and adrenal toxicity From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 105 106 Russell E. Lewis and Annette W. Fothergill Fig. 6.1. Representative structures of systemic antifungal agents. 6. Antifungal Agents 107 • Limited penetration into anatomically restricted sites such as the cerebrospinal fluid (CSF) In an attempt to address these limitations, a new chemical group of azoles was developed (triazoles) with improved physiochemical characteristics and spectrum of activity. Fluconazole, the first triazole introduced on the market in early 1990s, could be administered intravenously or orally and had predictable pharmacoki- netics, excellent oral bioavailability, and improved penetration into anatomically restricted sites such as the vitreous humor and CSF. Importantly, fluconazole was well tolerated and was associated with few serious drug interactions in critically- ill patients. As a result, during the 1990s fluconazole quickly became one of the most widely prescribed antifungal agents for superficial and life-threatening infections due to yeast (1). The lack of activity against opportunistic moulds (i.e., Aspergillus, Fusarium, and the Zygomycetes) and intrinsic resistance among some non-albicans Candida species (Candida glabrata and Candida krusei), however, created a need for broader-spectrum alternatives in the treatment of severely immunocompromised patients. The development of itraconazole and the broader-spectrum triazole deriva- tives, voriconazole and posaconazole, has largely addressed the spectrum limitations of fluconazole among these high-risk patients. Yet, these broader spectrum triazoles still carry a potential for cross-resistance with fluconazole (2) and exhibit more complex pharmacokinetic profiles, and a higher propensity for drug interactions. Hence, less toxic alternatives to triazole antifungal therapy would be desirable in critically ill patients, especially patients at higher risk of pharmacokinetic drug–drug interactions. The final milestone of antifungal drug discovery during the 20th century was the identification and development of the echinocandins, lipopeptide molecules that inhibit glucan synthesis leading to damage of the cell wall (3). Because of the importance of the fungal cell wall survival and the lack of this target in mammalian cells, echinocandins were predicted to be well tolerated antifungal agents with little collateral toxicity in humans. Yet, the first echinocandin tested in humans, cilofungin, had to be abandoned before large-scale clinical trials owing to difficulties in its preparation and the toxicity of its intravenous formulation (4). Subsequent semisynthetic echinocandin derivatives demonstrated improved solubility and potency and were well tolerated even at high dosages. In 2001, caspofungin became the first echinocandin approved by the US Food and Drug Administration (FDA) for the treatment of invasive fungal infections in humans. Two other echinocandin derivatives with a similar spectrum as caspofungin, anidulafungin and micafungin, subsequently progressed through Phase III clinical trials and have been approved or have pending approval for clinical use in patients with oroesophageal candidiasis or invasive candidiasis. Although the arrival of new antifungal agents has clearly advanced the management of invasive fungal infections, drug therapy failures are still common and many patients may not tolerate particular antifungal agents because of hypersensitivity reactions, renal or hepatic toxicity, or the potential for serious drug interactions. Therefore, no single antifungal agent is appropriate for all patients for any given mycosis. Moreover, break- through infections with intrinsically resistant pathogens have become more common with 108 Russell E. Lewis and Annette W. Fothergill prolonged treatment courses and improved survival of chronically immunocompromised hosts. This trend has created an urgent need for laboratory support in the treatment of invasive fungal infections including (1) the rapid identification of fungal pathogens to the species level, and where appropriate, (2) in vitro susceptibility testing of clinical isolates to guide the selection of antifungal therapy. This chapter reviews key compo- nents of antifungal pharmacology with a special emphasis on systemic antifungal agents and common resistance patterns among opportunistic mycoses in humans. 2. TARGETS OF ANTIFUNGAL THERAPY Despite differences in the composition of the cell membrane and the presence of a cell wall, much of the cellular machinery of fungi shares remarkable homology to mammalian cells. Consequently, development of drugs that selectively target pathogenic fungi without producing collateral damage to mammalian cells is a daunting pharmacological challenge. Indeed, many of the toxicities and drug interactions observed with contemporary antifungal therapies can be attributed to “nonselective” interactions with homologous enzyme or cell membrane systems found in mammalian host cells (5). With the exception of flucytosine, currently available systemic antifungals act primarily through direct or indirect interactions with the fungal cell wall and plasma membrane, and the fungal membrane sterol ergosterol and its biosynthetic pathways (Fig. 6.2). The fungal cell envelope has several properties that make it an ideal target for antifungal therapy (4): Fig. 6.2. Targets of antifungal therapy. [Figure in color on CD-ROM]. 6. Antifungal Agents 109 • In contrast to the cholesterol-rich cell membranes of mammalian cells, the predom- inant cell membrane sterol in pathogenic fungi is ergosterol. Indirect or direct targeting of ergosterol results in selective toxicity to the fungal cells. • Mammalian cells lack a true cell wall. Drugs that target synthesis of the fungal cell wall have a low potential to cause collateral toxicity in mammalian cells. • The cellular wall and membranes are important for ion exchange, filtration, and are a critical area for localization of enzymes involved in the metabolism and catabolism of complex nutrients (6). Drugs that disrupt growth of the cell membrane and wall produce a number of pleotropic effects are selectively lethal to fungi. 2.1. Polyene Mechanisms of Action Polyene antifungals (amphotericin B) bind to ergosterol, the principal sterol in the fungal cell membrane, disrupting the structure of the fungal cell membrane to the point of causing leakage of intracellular contents. Although this binding typically results in rapid cell death, the precise mechanism of fungicidal activity remains unknown. Structurally, the fungal sterol ergosterol exhibits a more cylindrical three-dimensional structure than the mammalian sterol cholesterol, which largely explains the greater affinity of amphotericin B binding to ergosterol (Fig. 6.3) (4). However, amphotericin B also can bind to cholesterol in mammalian cell membranes; a mechanism that could account for the direct toxicity of the drug to the distal tubules of the kidney (5). 2.2. Azole Mechanisms of Action In contrast to the direct interactions of the polyene antifungals with ergosterol, azole antifungals indirectly affect the fungal cell membrane through inhibition of ergosterol biosynthesis. Azole antifungal compounds inhibit cytochrome P-450 sterol 14-demethylase (Erg11p or CYP51p depending on nomenclature), an enzyme that catalyzes the oxidative removal of 14-methyl group of lanosterol in the ergosterol Fig. 6.3. Amphotericin B, ergosterol and cholesterol visualized in three dimensions. [Figure in color on CD-ROM]. 110 Russell E. Lewis and Annette W. Fothergill biosynthetic pathway. Inhibition of 14-demethylase by azoles results in an accumu- lation of 14-methylated sterols in the cytoplasmic membrane, which disrupt phospho- lipid organization and impair membrane-bound enzyme systems such as ATPase and enzymes of the electron transport system, thus arresting fungal cell growth. CYP51p enzyme binding is accomplished through coordination of the triazole nitrogen, N3 or imidazole N4 of the azole ring with the cytochrome P-450 heme target site, while the remainder of the drug molecule binds to the apoprotein in a manner dependent on the individual structure of the azole (Fig. 6.4) (4). Differences in the exact confor- mation of the active site between fungal species and drug structure largely define the spectrum of each agent. For molecules derived from the ketoconazole pharmacophore (e.g., itraconazole, posaconazole), extension of the side chain enhances binding of the azole to the P450 apoprotein, and expands the potency and spectrum against both yeast and filamentous fungi. For molecules derived from fluconazole (e.g., voriconazole) inclusion of an -O-methyl group confers activity against Aspergillus and other filamentous fungi (7). One drawback of targeting fungal CYP-450 enzymes involved in ergosterol biosyn- thesis is the homology the fungal enzyme systems share with mammalian CYP 450 enzymes involved in drug metabolism (Fig. 6.4). Indeed, all azoles inhibit to varying degrees the mammalian CYP P450 enzymes involved in drug metabolism (8). Azole therapy can predispose patients to a number of clinically significant pharmacokinetic drug–drug interactions when these antifungals are administered concurrently with drugs that are either substrates or inducers of CYP P450 enzymes in humans. Unfortunately, modifications of the azole pharmacophore designed to enhance binding to fungal CYP51p frequently enhance binding of mammalian CYP P450 enzymes. Therefore, Fig. 6.4. Cyp51p and CYP P450 3A4 visualized in three dimensions highlighting the heme binding site for the imidazole (ketoconazole) and triazole rings. [Figure in color on CD-ROM]. 6. Antifungal Agents 111 improvement in the spectrum of

azole antifungals is often accompanied by an increased potential for drug interactions. 2.3. Allylamine Mechanisms of Action Similar to azoles, allylamines inhibit ergosterol biosynthesis before 14 - demethylase by inhibition of the squalene monooxygenase (formally epoxidase). This enzyme is responsible for conversion of squaline to squalene epoxide, a precursor of lanosterol in the ergosterol biosynthetic pathway. After exposure to allylamines such as terbinafine, the fungal cell membrane accumulates squalene while becoming deficient in ergosterol, resulting in arrest of cell growth. Although allylamines do not appear to produce the same degree of cross-inhibition of mammalian CYP P450 enzymes as azole antifungals, strong inducers of mammalian CYP-P450 enzymes such as rifampin still increase the metabolism of squalene monooxygenase inhibitors such as terbinafine. 2.4. Echinocandin Mechanisms of Action Of the currently available antifungal agents, only one class of agents, the echino- candins, are known to specifically target fungal cell wall synthesis. Echinocandins inhibit the synthesis of 1,3--d-glucan polymers, which serve as essential cross-linking structural components of the cell wall. Depletion of 1,3--d-glucan polymers in suscep- tible fungi leads to an structurally impaired cell wall, osmotic instability, and lysis in rapidly growing cells. The presumed target of the echinocandins is thought to be -1,3- d-glucan synthase, although formal proof of this target in pathogenic fungi has been complicated by technical difficulties in studying the membrane-bound protein complex. In Saccharomyces cerevisiae, where the enzyme complex has been best studied, the echinocandins are known to bind to the Fks1p component of the two proteins (Fks1p and Fks2p) regulated by the GTP-binding peptide, Rho1p, that comprise the trans- membrane -1,3-d-glucan synthase complex (9). The degree of -1,3-d-glucan polymerization in the cell wall and expression of the -1,3-d-glucan synthase target chiefly defines the spectrum and lethality of the echinocandins in pathogenic fungi. In Candida species, the fungal cell wall is rich in -1,3-d-glucans and the enzyme complex is highly expressed during rapid cell growth. Hence, echinocandins exhibit fungicidal activity against most rapidly growing Candida species. However, echinocandins lack clinically useful activity against Crypto- coccus neoformans owing in part to the limited use of -1,3-d-glucan in the cell wall of this species (10). Among hyaline moulds, the cell wall of Aspergillus species contain the greatest degree of -1,3- and -1,6-d-glucan polymers. The -1,3-d-glucan synthase complex, is expressed predominantly on the growing apical tips of the hyphae. Therefore, echinocandins kill only the growing hyphal tips of the fungus, resulting in abnormal, hyperacute branching and aberrant growth, with minimal effects on the viability of subapical components (Fig. 6.5) (11). Other filamentous fungi such as Fusarium species and Zygomycetes utilize -1,3-glucans in the cell wall matrix and chitosan polymers (10). As such, echinocandins lack pronounced activity in vitro against these opportunistic fungi. 112 Russell E. Lewis and Annette W. Fothergill Fig. 6.5. In vitro effects of caspofungin (CAS) on fungal morphology. 2.5. Pyrimidine Mechanisms of Action Flucytosine (5-fluorocytosine, 5-FC) works as an antifungal agent after conversion to 5-fluorouracil within fungal cells (Fig. 6.2). Once inside cells, 5-fluorouracil inhibits thmidylate synthase, a key enzyme in DNA synthesis, and incorporates into RNA, causing premature chain termination. The uptake and conversion of flucytosine requires the activity of two enzymes, cytosine permease and cytosine deaminase. Mammalian cells and many filamentous fungi lack or have very low activity of these enzymes, thus restricting the activity of the flucytosine to pathogenic yeast (5). In humans, however, resident intestinal flora may convert flucytosine to fluorouracil, resulting in nausea, vomiting, diarrhea, and bone marrow suppression (5). 3. ANTIFUNGAL RESISTANCE Antifungal resistance is a broad concept describing the failure of a fungal infection to respond to antifungal therapy. Resistance has been traditionally classified as either primary (intrinsic, i.e., present before exposure to antifungal) or secondary (acquired, i.e., that which develops after antifungal exposure owing to stable or transient genotypic alterations) (12,13). A third type of antifungal resistance could be described as “clinical resistance,” which encompasses progression or relapse of infection by a pathogenic fungus that appears, by laboratory testing, to be fully susceptible to the antifungal agent used to treat the infection. Clinical resistance is most commonly a result of persistent and profound immune defects (e.g., AIDS, neutropenia, graft versus host disease and its treatment) or infected prosthetic materials (i.e., central venous catheters), which become encased in protective biofilm, thus limiting drug activity (12,13). In some cases, suboptimal drug concentrations at the site of infection resulting from poor drug absorption, drug interactions, or infrequent dosing may contribute to clinical resistance. Primary or secondary antifungal resistance can arise through a number of complex mechanisms and may be expressed over a wide phenotypic spectrum (12). At one extreme, fungi may be susceptible to the effects of an antifungal agent but growth may not be completely inhibited in vitro. This so-called trailing growth may be observed 6. Antifungal Agents 113 for antifungals during laboratory testing (particularly azoles and flucytosine) even at high concentrations, but is generally considered a testing artifact and not indicative of true resistance. Similarly, some echinocandins may exhibit a paradoxical attenuation of activity at higher drug concentrations without clear evidence of diminished drug activity at higher dosages in animal models or patients. Heterogeneous resistance, the presence of subpopulations of fungal cells with varying degrees of resistance to an antifungal agent in a susceptible population, may indicate an increased propensity for the devel- opment of antifungal resistance. This type of resistance may not be detected unless specialized testing methods are used in the laboratory. Inducible or transiently expressed (epigenetic) antifungal resistance mechanisms have also been described in fungi, but little is known about the clinical significance of these resistance patterns in human infections (12). The other extreme in the phenotypic expression of antifungal resistance is represented by isolates with stable and persistent growth even at high antifungal concentrations. It is important to note that most studies of antifungal resistance focus on isolates with a stable resistance phenotype. Molecular mechanisms of resistance have been best described in C. albicans isolates recovered from AIDS patients with chronic, recurring fluconazole-refractory oropharyngeal candidiasis (13). The chronic nature of these mucosal infections allows the longitudinal collection of serial, matched Candida isolates that exhibit progressively stable, higher degrees of resistance to antifungals. By contrast, acute bloodstream candidiasis, aspergillosis, or other less common life-threatening mycoses do not typically allow for the study of serial, matched isolates, thus complicating genotypic–phenotypic correlation of resistance development. 3.1. Laboratory Detection of Resistance Standardization of in vitro tests used to determine the activity of antifungals has been a long process. In 1982, the Clinical Laboratory and Standards Institute (CLSI, formerly NCCLS) established a subcommittee to assess the need for such testing. It was not until 1985 that the first report of this subcommittee was released. That document, NCCLS M20-CR, Antifungal Susceptibility Testing; Committee Report, was based on responses from hospitals and reference laboratories from across the nation. The committee found that approximately 20% of the laboratories that responded were in fact conducting antifungal susceptibility testing. Many methods existed, but most of the respondents utilized a broth method and were testing yeast only. Comparison testing of isolates between collaborating laboratories was unacceptably low. Based on this study, the decision was made to develop a standardized method, the goal being to correlate not between isolate and patient outcome but rather between laboratories. Methods that existed included broth, agar, and disk diffusion. The committee decided that the standard method should be a macrobroth dilution method and that only a synthetic medium should be chosen. Several centers collaborated and a preliminary method was introduced in 1992, M27-P (14). Parameters were set to include medium, inoculum preparation and size, incubation temperature and duration, and end point criteria. The procedure has been refined and is now an approved method, M27-A2 (15). Subsequent publications include M38-A (16) and M44-A (17). M38-A utilizes similar methods for mould testing while M44-A provides guidelines for disk 114 Russell E. Lewis and Annette W. Fothergill diffusion testing of yeast. As a result of approved methods, industry now provides kits that enable routine microbiology laboratories to perform testing in-house rather than sending isolates off for reference testing. Before doing this, however, laboratories should have sufficient requests for this testing to ensure the volume of work needed to maintain accuracy and reproducibility. Interpretive guidelines have been established only for fluconazole, itraconazole, and 5-fluorocytosine. Categories for 5-fluorocytosine include susceptible (S), intermediate (I), and resistant (R) while those for the azoles include susceptible (S), susceptible dose- dependent (SDD), and resistant (R). The susceptible dose-dependent category relates to yeast testing only and is not interchangeable with the intermediate category associated with bacterial and 5-fluorocytosine breakpoints. This category is in recognition that yeast susceptibility is dependent on achieving maximum blood levels. By maintaining blood levels with higher doses of antifungal, an isolate with an SDD endpoint may be successfully treated with a given azole (17). One important problem with any approach toward in vitro susceptibility testing is the correlation of the minimum inhibitory concentration (MIC) with patient outcome. Some assumptions can be made, however, about MIC and patient outcome. Rex and Pfaller proposed the “90–60 Rule” as a general guide for establishing clinically relevant interpretative breakpoints for resistance (18). This rule states that infections caused by isolates that have MICs considered susceptible respond favorably to appropriate therapy approximately 90% of the time whereas infections caused by isolates with MICs considered resistant respond favorably in approximately 60% of cases. 3.2. Mechanisms of Resistance Many aspects of antifungal resistance are still poorly understood, particularly with respect to the regulation and expression of resistance mechanisms after exposure to antifungal agents (secondary resistance). Nevertheless, advances in molecular biology and genome sequencing of pathogenic fungi have yielded progress in our understanding of the mechanisms most frequently leading to antifungal resistance. These mechanisms can be grouped into five general categories (Fig. 6.6): • Decreased drug import or increased drug export (efflux pumps) • Alteration in drug target binding site • Changes in biosynthetic pathways (particularly sterol synthesis) that circumvent or attenuate the effects of antifungal inhibition • Alterations in intracellular drug processing • Upregulation of homeostatic stress-response pathways to deal with antifungal- associated damage It is important to note that multiple resistance mechanisms are often expressed simulta- neously after antifungal exposure and that a single mechanism is unlikely to result in a resistant strain. Depending on the mechanisms concurrently expressed, cross-resistance may or may not be observed between different antifungals. Whole genome expression profiles of C. albicans have revealed transient upregulation of several resistance mecha- nisms (i.e., ergosterol biosynthesis— ERG 3, ERG11; efflux pumps—CDR1, CDR2) following a single exposure to azole antifungals (19). Development of resistance in 6. Antifungal Agents 115 Fig. 6.6. Mechanisms of antifungal resistance. [Figure in color on CD-ROM]. longitudinally collected clinical strains in patients who fail a course of progressively higher dosages of antifungals generally demonstrates a gradual accumulation of several alternations that result in a detectable resistance (12). Changes in drug import and export are probably the most common mechanisms associated with primary and secondary antifungal resistance (12). Decreased drug import is consistently associated with primary resistance to flucytosine and azole antifungals. For example, poor uptake of flucytosine due to alterations in cytosine permease or decreased availability of this enzyme largely accounts for the limited spectrum of this agent against opportunistic moulds. Similarly, differences in azole susceptibility between fluconazole and itraconazole against C. krusei have been reported to be more closely associated with intracellular accumulation than differ- ences in drug binding affinity to the 14-demethylase target (20). Drug import may also be affected by the sterol composition of the plasma membrane. Several studies have demonstrated that when the ergosterol component of the membrane is altered in favor of other 14-methyl sterols there is a concomitant permeability change in the membrane to antifungals and a decrease in membrane fluidity (12). 116 Russell E. Lewis and Annette W. Fothergill Similar to other eukaryotic cells, fungi are known to contain two types of efflux pumps that contribute to drug resistance: ATP binding cassette (ABC) transporters and major facilitators (MF). Overexpression of the ATP-dependent ABC transporters typically confers a multidrug resistance phenotype. In contrast, MF pumps, which expel antifungal though protonmotive force (H+ gradient across membrane), have a much narrower spectrum of substrate specificity. In Candida albicans, overexpression of ATP-dependent efflux pumps CDR1 and CDR2 confer cross-resistance to all azole antifungals (12). In contrast,

overexpression of MF pump MDR1 affects only the accumulation of fluconazole and does not result in cross-resistance to itraconazole or ketoconazole. Overexpression of ATP-dependent efflux pumps is the most prevalent mechanism of efflux-mediated resistance reported in clinical isolates (12). Recently, overexpression of ABC transporters was reported to confer a degree of cross-resistance between azoles and echinocandins in a laboratory strain of C. albicans (21). Besides drug efflux, the most common mechanism associated with antifungal resis- tance involves changes in the binding site of the drug. Several genetic alternations in ERG11, the gene encoding 14-demethylase, have been attributed to decreases in azole activity, including point mutations that result in changes in the active pocket site or overexpression of ERG11. Similar alterations in other enzymes of the ergosterol biosynthetic pathway, particularly ERG 3 (C-5-sterol desaturase), which is upregu- lated with inhibition of 14-demethylase, have also been documented in azole-resistant clinical strains. Binding site alteration is also likely to be an important mechanism of echinocandin resistance. Point mutations in the FKS1 gene have been reported in laboratory-derived caspofungin-resistant mutants of C. albicans (3). Changes in the target expression in the ergosterol biosynthetic pathway alter the fungal cell membrane sterol content. Substitution of alternative sterols for ergosterol, or alterations in the sterol:phospholid ratio in the cell membrane, can decrease intra- cellular accumulation of azoles and reduce the binding of amphotericin B to the cell membrane. Indeed, many polyene-resistant yeasts recovered from patients with clear microbiological failure on amphotericin B have dimished ergosterol concentrations in their fungal cell membranes. Several studies have even suggested that pathogenic fungi can scavenge free sterols for the cell membrane, including cholesterol, resulting in resistance to polyene and azole antifungals (22). Alterations in intracellular drug processing and/or degradation and metabolism are probably the least well studied pathways of resistance in fungi, even though these mechanisms are well characterized in other prokaryotic and eukaryotic systems. Resistance to flucytosine has been associated with alterations in cystosine deaminase, which results in decreased intracellular conversion of flucytosine to its active form. Recent studies of antifungal resistance have begun to focus on homeostatic stress- response pathways in fungi that may be unpregulated after exposure to antifungals. Disruption of the evolutionarily conserved protein kinase C (PKC) cell wall integrity and calcineurin pathways enhances azole and echinocandin killing in fungi (23). Upreg- ulation of these pathways also diminishes the lethal effects of antifungals through upregulation of ergosterol and glucan biosynthesis, increases in chitin content in the fungal cell wall, as well as increased export of cell wall components for cell wall repair. 6. Antifungal Agents 117 Recently, the molecular chaperone heat shock protein 90 (Hsp90) was reported to play a critical role in regulating resistance to antifungal agents through the calcineurin pathway (24,25). Future efforts toward combating antifungal resistance are likely to exploit this important and evolutionarily conserved mechanism for maintaining and expressing resistance mechanisms to antifungals. 4. AMPHOTERICIN B Conventional amphotericin B (Fungizone®) has long been considered to be the cornerstone of therapy for deeply invasive fungal infections. Toxicity, including infusion-related fever, chills, rigors, headache, and dose-limiting nephrotoxicity, often limits the effectiveness of this agent in severely ill patients. Consequently, three lipid-based formulations (Ambisome®, Abelcet®, Amphotec®) were developed that offer several advantages over conventional amphotericin B including (1) the ability to administer higher daily dosages of drug, (2) decreased infusion-related side effects (especially for the liposomal formulation), and (3) a reduced rate of nephrotoxicity (Table 6.1). Despite the improved therapeutic index of these formulations, there is still relatively few data from prospective clinical trials to suggest these formulations are more effective than conventional amphotericin B. Moreover, the higher acquisition cost of the lipid formulations has required many institutions to restrict the use of these formulations to patients with preexisting renal failure, or in patients who are at high risk for developing nephrotoxicity while receiving amphotericin B (e.g., patients on concomitant nephrotoxic therapies). Currently, there is no consensus opinion on the clinical or pharmacoeconomic threshold for using lipid amphotericin B formulations as first-line therapy for most invasive mycoses. 4.1. Spectrum and Susceptibility Amphotericin B should be administered only to patients with progressive and possibly fatal infections. Acceptable activity can be measured in vitro against almost all fungi including Candida, Cryptococcus, Aspergillus, Blastomyces, Histo- plasma, Coccidioides, Sporothrix, and agents of zygomycosis (mucormycosis, including Rhizopus, Mucor, and Absidia), as well as other less frequently recovered strains. A few species exhibit elevated MICs when tested against amphotericin B and are known to possess innate resistance to this drug. Resistant species include both Scedosporium apiospermum and S. prolificans in addition to Paecilomyces lilacinus, Aspergillus terreus, and some Fusarium species. Early reports have revealed Candida lusitaniae resistance to amphotericin B and have shown that this species possesses the ability to develop resistance while the patient is on treatment. The first report involved a patient whose initial isolate was susceptible but whose subsequent isolates had developed amphotericin B resistance (26). Later reports have shown ampho- tericin B resistance may exist even before exposure to amphotericin B (27). The expected rate of resistance for C. lusitaniae is 8% to 10% of any microbiology lab stock collection. Table 6.1 Systemic antifungal therapies Antifungals Trade name(s) Usual adult dose Mechanism of action Toxicities Spectrum/comments Polyenes Amphotericin B Fungizone 0.25–1.5 mg/kg IV q24h Bind to ergosterol and Acute—Fever, chills, rigor, Drug of choice for severe infections caused intercalates with the arthralgia with infusion. by endemic dimorphic fungi, most fungal cell membrane, Thrombophlebitis, dyspnea Candida species, and common resulting in increased (rare), arrhythmias (rare) hyalohyphomycetes (including membrane permeability Aspergillus) and zygomycosis. to univalent and divalent cations Delayed—Azotemia (26%), Nephrotoxicity is the dose-limiting tubular acidosis, side-effect, reduced with lipid hypokalemia, amphotericin B formulations and saline hypomagnesemia, anemia pre and post hydration. Lipid formulations of amphotericin B: Liposomal (L)- AMB Ambisome, 3–10 mg/kg q24h Infusion related reactions: Ambisome ABLC Abelcet, 5 mg/kg/q24h < Abelcet < Amphotec ABCD Amphotec 3–4 mg/kg q24h Azoles Ketoconazole Nizoral 200–800 mg PO q24h Inhibition of Gastrointestinal (20–50%) Oral formulation only. Inconsistencies in cytochrome P450 including nausea and oral absorption/poor gastrointestinal Divided doses 14-demethylase, vomiting, anorexia, rash tolerance limits use for treatment of recommended ≥ 400 decreased production (2%), transient increases in deep mycoses. Potent inhibitor of mg/day of ergosterol, hepatic enzymes, severe mammalian cytochrome P450 can lead to accumulation of hepatotoxicity (rare), potentially severe drug interactions when lanosterol leading to alopecia, inhibition of administered concomitantly with other perturbation of adrenal steroid synthesis P450-metabolized drugs. fungal cell (especially at dosages > membrane, 600 mg/day) fungistatic Itraconazole Sporanox 200–400 mg PO q24h Similar to Gastrointestinal (20%) Spectrum similar to fluconazole with IV 200–400 mg q12h, ketoconazole, but including nausea enhanced activity against C. krusei and then q24h more selective for and vomiting, and Aspergillus. Not active against Fusarium fungal P450 diarrhea, rash (2%), taste and zygomycosis. Drug of choice for mild Divided doses demethylase disturbance (oral solution), to moderate infections caused by endemic recommended ≥ 400 transient increases in dimorphic fungi. Bioavailability of oral mg/day hepatic enzymes, severe solution is improved over capsules by hepatotoxicity (rare), 30% under fed conditions and 60% in alopecia, inhibition fasting conditions. Potent inhibitor of of adrenal steroid mammalian cytochrome P450 enzymes. synthesis (especially at Serum level monitoring is occasionally dosages > 600 mg/day). recommended, trough levels measured by Accumulation of hydroxy- HPLC should exceed 0.5 μg/ml propyl--cyclodextran vehicle in patients with CrCl < 30 ml/min (intravenous formulation). Congestive heart failure (rare) (Continued) Table 6.1 (Continued) Fluconazole Diflucan 3–12 mg/kg PO/IV Similar to Gastrointestinal (5–10%), Spectrum includes most Candida species, q24h ketoconazole, but more rash, headache, transient Cryptococcus neoformans, and endemic selective inhibitor of increases in hepatic enzymes, dimorphic fungi. Less active against Dosage adjustment 14 demethylase hepatotoxicity (rare), alopecia Candida glabrata. Candida krusei is required in renal intrinsically resistant. Not clinically active impairment for deep mycoses caused by invasive moulds. Higher daily dosages are recommended (e.g., 12 mg/kg per day) in critically-ill patients or in institutions where Candida glabrata is common Voriconazole Vfend 6 mg/kg IV q12h × 2 Similar to fluconazole, Transient photopsia Spectrum similar to itraconazole with doses, then 4 mg/kg but higher affinity (reported up to 30%), rash, enhanced activity against Aspergillus, q12h for fungal hallucinations (2%), transient Fusarium, and Scedosporium apiospermum 14-demethylase increases in hepatic enzymes, (Pseudallescheria boydii). Retains activity 200 mg PO q12h if > severe hepatotoxicity against some fluconazole-resistant 40 kg, 100 mg PO (rare).Accumulation of C. glabrata. Inhibitor of mammalian q12h if < 40 kg sulfo-butyl ester cyclodextran cytochrome P450 enzymes. vehicle may occur in patients with CrCl < 50 ml/min receiving intravenous formulation. Posaconazole Noxafil 600–800 mg/day in Similar to voriconazole Gastrointestinal (5–15%), Spectrum similar to voriconazole with divided doses fever, headache, enhanced activity against Fusarium, musculoskeletal pain (5%) zygomycosis, and black moulds (phaeohyphomycetes). Inhibitor of mammalian cytochrome P450 3A4 (Continued) Echinocandins Caspofungin Cancidas 70 mg IV day 1, then Inhibition of cell wall Fever, chills, Spectrum includes most Candida 50 mg q24h glucan synthesis, phlebitis/thrombophelibitis species including fluconazole-resistant leading to osmotic (peripheral line), rash. Candida krusei and Candida glabrata. instability of fugal Drug concentrations Higher dosages may be required for cell. decreased with P450 3A4 C. parapsilosis. Active against inducers. Decreases Aspergillus species.Not active against tacrolimus blood levels by Cryptococcus neoformans, Trichosporon, ∼25% Fusarium, zygomycosis, or black moulds (phaeohyphomycetes). Micafungin Mycamine 50–150 mg IV q24h Similar to caspofungin Clearance not affected by Similar to caspofungin P450 3A4 inducers Anidulafungin Eraxis 200 mg IV day 1 then Similar to caspofungin Clearance not affected by Similar to caspofungin 100 mg/day P450 3A4 inducers Fluoropyrimidines Flucytosine Ancobon 100 mg/kg daily PO Drug is transported into Increase in serum Narrow spectrum for deep mycoses: (5-FC) divided q6h Dosage susceptible fungi by transaminases (7%), nausea Candida and Cryptococcus neoformans adjustment required in cytosine permease, and vomiting (5%); only. Resistance is common when used as renal impairment and then deaminated diarrhea, abdominal pain, monotherapy. Typically administered in to active form rash, entercolitis (rare)Less combination with amphotericin B for (5-FU) by cytosine common- leucopenia, cryptococcal meningitis.Risk of bone deaminase where the thrombocytopenia, anemia marrow suppression increased with drug interferes with persistent flucytosine levels >100 μg/ml. DNA/RNA synthesis Careful dosage adjustment is required in patients with renal dysfunction. PO, Orally; IV, intraveneously; q6h, every 6 hours; q12h, every 12 hours; q24h, every 24 hours; P450, cytochrome P450. 122 Russell E. Lewis and Annette W. Fothergill 4.2. Pharmacokinetics Amphotericin B deoxycholate has negligible oral absorption and must be admin- istered intravenously. After intravenous administration, the drug is released from its carrier and is highly bound by plasma proteins (91% to 95%) including lipoproteins, erythrocytes, and cholesterol in the plasma. Amphotericin B then redistributes from the bloodstream into tissue with an apparent volume of distribution (Vd) of 4 liters/kg (5). In adults, infusion of 0.6 mg/kg of amphotericin B deoxycholate yields peak serum concentrations of approximately 1 to 3 μg/ml (28). Concentrations in other body fluids outside the serum are less than 5% of concurrent serum concentrations, with poor penetration into bronchial secretions, pleura, peritoneum, synovium, and aqueous humor. Although amphotericin B poorly penetrates the CSF, fungal infections of the brain have been successfully treated with amphotericin B (5). Tissue concentrations of amphotericin B are highest in the kidney, followed by the liver, spleen, heart, skeletal, muscle, and brain. The formulation of amphotericin B into phospholipid sheets (Abelcet), cholesterol disks (Amphotec), or liposome carriers (Ambisome) alters drug distribution (particularly to the kidney) and the elimination profile of the drug (5) (Table 6.2). Recent studies have suggested that amphotericin B undergoes relatively little metabolism, with a terminal elimination half-life of greater than 11 to 15 days. After 168 hours, approximately 60% of a single dose can be recovered from the feces (∼40%) and urine (20%) (29). Because a relatively lower fraction of the daily dosage is slowly excreted in urine and bile, dosage modification is not necessary to prevent drug accumulation in patients with renal or hepatic failure, but may be judicious in a patient with declining renal function. Because amphotericin B behaves as a colloid in aqueous solutions and is highly protein bound, hemodialysis does not remove significant amounts of the drug unless the patient is hyperlipidemic; which enhances amphotericin B binding to the dialysis membrane (5). 4.3. Adverse Effects The most common acute toxicity of amphotericin B formulations is infusion-related reactions, which are characterized by fever, chills, rigors, anorexia,

nausea, vomiting, myalgias, arthralgias, and headache. Hypotension, flushing and dizziness are less common, but bronchospasm and true anaphylactic reactions have been reported with both the conventional and lipid formulations of amphotericin B (5). Severe hypokalemia and cardiac arrhythmias have also been described in patients with central venous catheters who have received rapid infusions or excessive doses of conventional ampho- tericin B. Therefore, slower infusion rates (4 to 6 hours or more) and EKG monitoring should be considered in patients with underlying cardiac conduction abnormalities. Thrombophlebitis is a common local side effect with infusion, which often necessi- tates the placement of a central venous line for therapy more than 1 week. Slower infusion rates, rotation of infusion sites, application of hot packs, low-dose heparin, and avoidance of concentrations greater than 1 mg/ml can minimize thrombophlebitis. Acute reactions generally subside over time and with subsequent amphotericin B infusions. In the past, a test dose of amphotericin B deoxycholate (i.e., 1 to 5 mg) was recommended before initiating therapy. This is no longer considered Table 6.2 Comparative pharmacokinetics of the antifungal agents AMB ABCD ABLC L-AMB Flu Itraa Vori Posa Anid Cas Mica 5FC Oral bioavailability (%) <5 <5 <5 <5 95 50 96 60 <5 <5 <5 >80 Distribution Total Cmax (μg/ml) 4 0.3–1 131 0.7 11 4.6 7.8 0.83 0.27 0.24 80 AUC (mg * h/L) 17 43 14 555 400 29.2 20.3 8.9 99e 119 158e Protein binding (%) >95 >95 >95 >95 10 99.8 58 99 84 97 99 4 CSF (%) 0–4 >60 <10 60 <5 <5 <5 75 Eye (%) 0–38bc 0–38bc 0–38bc 0–38bc 28–75bc 10†(0.22 18b(0.81 26(0.25 ND ND ND ND (10–70 μg/ml) μg/ml) μg/ml) μg/ml) Urine (%)d 3–20 4.5 90 1–10 <2 <2 <2 <2 <2 90 Metabolism Unk Unk Unk Unk + ++ +++ ++ None Hep Hep None Elimination Urine/ bile Unk Unk Unk Renal Hep Renal Feces Feces Urine Feces Renal Half-life (h) 50 30 173 100–153 31 24 6 25 24 30 15 3–6 AMB, amphotericin B deoxycholate; ABCD, amphotericin B cholesterol dispersion; ABLC, amphotericin B lipid complex; L-AMB, liposomal amphotericin B; Flu, fluconazole; Itra, itraconazole; Vori, voriconazole; Posa, posaconazole; Anid, anidulafungin; Cas, caspofungin; Mica, micafungin; 5FC, 5-fluorocytosine or flucytosine; ND, no data available; Unk, unknown; Hep, hepatic. aData are for oral solution. bHuman. cAnimal. d% of active drug or metabolites. eFor doses of 100 mg/day. 124 Russell E. Lewis and Annette W. Fothergill useful for screening patients for hypersensitivity reactions. Premedications such as low-dose hydrocortisone (1 mg/kg), diphenhydramine, meperidine (0.5 mg/kg), and nonsteroidal anti-inflammatory agents are often administered before amphotericin B infusions to blunt symptoms of acute reactions. Premedication is also recommended before infusions of the lipid amphotericin B formulations, despite the reduced rates of infusion reactions seen with these drugs. Nephrotoxicity is the most significant, delayed toxicity of amphotericin B and can be classified into glomerular or tubular mecha- nisms. Amphotericin B directly constricts the afferent arterioles, resulting in decreased renal blood flow and a drop in glomerular filtration (increased serum creatinine), eventually leading to azotemia. Amphotericin-induced azotemia can be reduced by ensuring patients are well hydrated before starting therapy and by sodium loading— the practice of administering intravenous normal saline (0.5 to 1 liters) before and after amphotericin B infusion to maintain renal blood flow and adequate glomerular filtration pressure. Two small nonrandomized studies have also suggested that the administration of amphotericin B deoxycholate by continuous infusion can preserve glomerular function in the short term (30,31); however, this dosing approach has not been widely adopted. Azotemia with amphotericin B is generally reversible, although 5% to 10% of patients may have persistent renal impairment after discontinuation of therapy. Amphotericin B is directly toxic to the distal tubules, resulting in impaired urinary acidification, impaired urinary concentrating ability, and wasting of potassium and magnesium. Hypokalemia is common in patients receiving either conventional or lipid formulations of the drug. Patients may require the administration of up to 15 mmol of supplemental potassium per hour (4). Hypokalemia and low serum magnesium levels frequently precede decreases in glomerular filtration (increased serum creatinine), especially in patients who are adequately hydrated or receiving lipid formulations of amphotericin B. Continued tubular damage, however, eventually results in decreases in renal blood flow and glomerular filtration through tubuloglomerular feedback mecha- nisms that constrict the afferent arteriole. Hence, sodium loading should still be considered for patients receiving lipid amphotericin B formulations. Patients who receive prolonged courses of amphotericin B frequently develop normochromic, normocytic anemia due to the inhibitory effects of amphotericin B on renal erythropoietin synthesis. Patients may experience decreases in hemoglobin of 15% to 35% below baseline that return to normal within several months of discontin- uation of the drug. Administration of recombinant erythropoietin may be required in patients with symptomatic anemia. 5. AZOLES The availability of azole antifungals, particularly the oral triazoles itraconazole, fluconazole, and more recently, voriconazole and posaconazole, fulfills a critical need for effective and better tolerated alternatives to amphotericin B. Miconazole was the first systemic azole approved for use in humans, but the relatively toxic intravenous formulation limited its use to severely ill patients. Similarly, ketoconazole was not effective in critically ill patients because of its lack of an intravenous formulation and erratic absorption in patients with relative achlorhydria. The triazoles have proven to be 6. Antifungal Agents 125 much more effective in the prevention and treatment of both primary and opportunistic mycoses. All three currently approved triazoles are available in table/capsule, oral solution, and intravenous formulations, providing clinicians with added flexibility in therapy selection. Because all azoles are potentially teratogenic, they should be avoided during pregnancy. 5.1. Spectrum and Susceptibility The triazoles are more easily tolerated, but are primarily considered fungistatic as opposed to fungicidal (lethal) drugs. However, clear definitions of cidality are often more difficult to ascertain with antifungal agents. Although similar in mechanisms of action, each agent has a slightly different spectrum of activity. Fluconazole is principally used for yeast infections including those caused by most Candida and Cryptococcus species. Although this drug has been used to successfully manage meningitis caused by Coccidioides, it is not typically a drug of choice for infections caused by other moulds. Of primary concern is acquired resistance by yeasts. Candida krusei is well documented to possess intrinsic resistance to fluconazole, so much so that susceptibility testing against this isolate is not recommended. Some reports place the rate of outright C. glabrata resistance at about 15% of any given population of isolates (32), but both C. albicans and C. glabrata are capable of developing resistance after prolonged therapy or after therapy with inappropriate dosing. Overall, by in vitro testing, about 88% of Cryptococcus neoformans and 95% of C. albicans strains appear susceptible to fluconazole. Itraconazole possesses a wide spectrum of activity, including activity against both yeasts and moulds. It is useful in treating aspergillosis, blastomycosis, coccidioidomy- cosis, histoplasmosis, and candidiasis. In addition, itraconazole possess low MIC end points against the dematiaceous fungi and may be considered the drug of choice for treatment of infections caused by fungi from this group. Cross-resistance is of concern between drugs within the azole class. Comparison of resistance patterns between itraconazole and fluconazole reveal similar percentages of resistance among Candida species. Voriconazole is noted to have activity against Aspergillus, S. apiospermum, and Fusarium solani. This is remarkable because both S. apiospermum and F. solani are notoriously resistant to other antifungal agents. In addition, voriconazole may possess lethal activity against the aspergilli as opposed to the static activity expected with the azoles. Susceptibility patterns with the yeasts are similar to those of both itraconazole and fluconazole. An important exception is the extremely low incidence of resistance seen with C. krusei, in contrast to near 100% resistance of this species to fluconazole and about 10% resistance to itraconazole. Posaconazole is a very promising investigational azole with a broad spectrum of activity. Clinical trials are underway to assess activity in aspergillosis, candidiasis, fusariosis, coccidioidomycosis, and zygomycosis (mucormycosis). Results against species such as Rhizopus and Mucor show that this drug may provide alternative therapy to amphotericin B for infections caused by this group of fungi. Resistance has not been noted but some cross-resistance may occur. 126 Russell E. Lewis and Annette W. Fothergill 5.1.1. Fluconazole Among the triazole antifungals, fluconazole (Diflucan®) is clearly the best tolerated agent and has the most desirable pharmacological properties including high bioavail- ability, high water solubility, low degree of protein binding, linear pharmacokinetics, and a wide volume of distribution including the CSF, eyes, and urine (27). Unlike other azoles, fluconazole is eliminated primarily unchanged through the kidneys and is less susceptible to clinically significant drug interactions through mammalian cytochrome P450 enzymes at standard dosages used to treat superficial (100 to 200 mg/day) or systemic (400 mg/day) infections. 5.1.2. Itraconazole Itraconazole (Sporanox®) was initially introduced in the early 1990s as a capsule formulation that was effective for superficial fungal infections and mild to moderately severe endemic mycosis, but erratic absorption in the critically ill patient limited its effectiveness for opportunistic mycoses. The subsequent reformulation of this triazole into an oral and intravenous solution with hydroxy--propyl cyclodextran signifi- cantly improved the blood levels that could be reliably obtained in critically ill and immunocompromised patients. Itraconazole is a relatively broad-spectrum triazole with activity against many common fungal pathogens including most Candida, Crypto- coccus, endemic dimorphic fungi (Histoplasma, Blastomyces , and Coccidioides), and Aspergillus. The drug is lipophilic, highly protein bound, and has a long half-life, nonlinear pharmacokinetics, and limited distribution into some body fluids, including the CSF and urine (Table 6.2). The drug is metabolized in the liver and to a lesser extent in the gut into more hydrophilic metabolites, one of which retains potent antifungal activity (hydroxyitraconazole). The most common adverse effects associated with itraconazole therapy are gastrointestinal (especially with the oral solution), rash, and transient increases in hepatic transaminases. Prolonged therapy can be associated with metabolic disturbances (suppression of adrenal steroid synthesis) and idiopathic congestive heart failure. Itraconazole is a substrate and potent inhibitor of mammalian cytochrome P450 enzymes and is therefore susceptible to a number of clinically signif- icant drug interactions (see Section 5.2, Azole Drug Interactions). 5.1.3. Voriconazole Voriconazole (Vfend®) is a methylated analogue of fluconazole with enhanced activity against yeast as well as important opportunistic moulds including Aspergillus and Fusarium (Table 6.1). Like fluconazole, voriconazole is well absorbed orally, has limited protein binding, and distributes widely throughout the body, including the CSF. Like itraconazole, intravenous voriconazole is formulated in a cyclodextran solution (sulfobutylether cyclodextran) and has nonlinear pharmacokinetics in adults. Voriconazole is metabolized to inactive metabolites through the liver and is an inhibitor of mammalian cytochrome P450 enzymes (Table 6.2). In addition to the common adverse effects seen with other triazole antifungals (gastrointestinal, rash, increases in hepatic enzymes), voriconazole can cause transient visual disturbances in 15% of 30% of patients that manifest as photophobia, perception of blinking or flashing lights (even with the eyes closed), and occasionally hazy or blurred vision. Symptoms tend 6. Antifungal Agents 127 to occur during the first week of therapy and disappear with continued therapy in most patients. Occasionally, visual disturbances are intensified by hallucinations—a separate side effect seen in 2% to 8% of patients receiving voriconazole (often with concomitant benzodiazepines and narcotic analgesic therapy). Visual disturbances are thought to be a result of temporary alterations in electrical conduction of photoreceptors in the rods and cones of the retina, which revert to normal once therapy is stopped. No permanent damage to the retina has been noted in human or animal studies of voriconazole (33,34). 5.1.4. Posaconazole Posaconazole (Noxafil®) is triazole analogue of itraconazole with enhanced activity against opportunistic moulds including Aspergillus, Fusarium, and (notably) the agents of zygomycosis. Posaconazole will initially be available as an oral suspension with an intravenous formulation still in development. Absorption of posaconazole suspension is dose limited at 800 mg/day and can be improved if the suspension is administered with a high-fat meal or in divided doses (twice to four times daily) (Table 6.1) (35). Once absorbed, posaconazole is widely distributed into tissues throughout the body and is highly protein bound (98%). Elimination of posaconazole occurs predominantly (90%) in the feces as unchanged drug and in the urine (10%) as an inactive metabolite (Table 6.2). Despite its lack of phase I metabolism, posaconazole is a potent inhibitor of

mammalian cytochrome P450 3A4 and has a similar potential for drug interactions as itraconazole when coadministered with drugs metabolized through this pathway. 5.2. Azole Drug Interactions As mentioned previously, an inherent limitation of azole pharmacology is that the target of antifungal activity in pathogenic fungi, the cytochrome P450 enzyme 14--demethylase, shares considerable homology with mammalian cytochrome P450 enzymes involved in drug metabolism. As a result, azole antifungals can be both substrates and inhibitors of cytochrome P450 systems in humans (8). Significant drug interactions with azole antifungals are summarized in Table 6.3. Many of these drug interactions are potentially severe and concomitant use should be avoided. Some azole drug interactions are less predictable and possibly dosage dependent. For example, fluconazole is a weak inhibitor of cytochrome P450 3A4 at dosages of 50 to 200 mg/day and is excreted primarily (80%) through the urine. However, as daily dosages are increased, fluconazole has a greater potential for inhibition of cytochrome P450 3A4 and a larger percentage of the drug is metabolized via the P450 system (8). Cytochrome P450 3A4 inducers increase metabolism of all azoles to varying degrees regardless of their primary excretion pathways. Coadministration of rifampin, for example, can reduce fluconazole serum concentrations by approximately 50% and concentrations of itraconazole, voriconazole, and posaconazole by greater than 90% (8). Azole antifungal therapy should be avoided, whenever possible, during use of high-dose conditioning chemotherapy with busulfan or cyclophosphamide owing to an increased risk of acute liver toxicity and accumulation of toxic chemotherapy metabolites (36). Although azoles themselves do not appear to exert major effects on cardiac conduction, their combined use with drugs that affect potassium channels and are metabolized through CYP 450 mechanisms (e.g., cisapride, haloperidol, certain tricyclic antidepressants) has the potential to cause life-threatening arrhythmias. 128 Russell E. Lewis and Annette W. Fothergill Table 6.3 Drug interactions of the azole antifungals. 6. ECHINOCANDINS Despite some modest differences in pharmacokinetics and potency, the echinocandins are pharmacologically similar and probably interchangeable (3). All three currently approved agents, caspofungin, micafungin, and anidulafungin, are large semisynthetic lipopeptides that are available only as intravenous formulations. All have linear pharmacokinetics, are widely distributed (with the possible exception of the CSF and urine), and have prolonged elimination half-lives that permit once-daily dosing. Slight differences in the metabolism and excretion are seen between the echinocandins, which may account for some differences in the drug interaction profile of these agents. 6.1. Spectrum and Susceptibility Caspofungin is indicated for candidiasis and for aspergillosis in patients who are refractory to other therapies. Use for infections caused by other moulds has not been as extensively studied. Activity is fungicidal against the yeasts while static against the aspergilli. End points against Aspergillus are determined differently than with other antifungals. End points are determined as minimum effective concentration (MEC). While growth is substantial with in vitro systems, it is evident that the growth is grossly abnormal. The MEC is considered the lowest concentration of drug that causes 6. Antifungal Agents 129 the abnormal growth of hyphae in this species (Fig. 6.5). End points for other moulds would be read in like manner. The echinocandins have not been evaluated by the CLSI (NCCLS) to standardize testing parameters. Many investigators feel that they should be tested in RPMI but results in RPMI are as high as six dilutions higher than results in antibiotic medium 3 (M3). Investigational animal studies do not support the results seen with RPMI and some researchers feel that the M3 results are more representative of true MICs. Resis- tance has not been widely reported for this class of antifungals. However, there are a few occurrences of isolates with high MICs. Candida parapsilosis and C. guillier- mondii are two species with notoriously increased MICs. Some clinical isolates of C. albicans and C. glabrata exist with elevated MICs but it is unclear if these isolates are truly resistant in vivo. Activity of the echinocandins is similar across the class. Micafungin has low MICs in both RPMI and M3 as opposed to caspofungin and anidulafungin, both of which exhibit high MICs in RPMI but lower results in M3. 6.2. Pharmacokinetics All three echinocandins are available as intravenous formulations only, have (mostly) linear pharmacokinetics, are widely distributed (with the possible exception of the CSF and urine), have prolonged elimination half-lives, and are metabolized by chemical degradation followed by hepatic metabolism (Table 6.2). Dosage adjustment is recom- mended for caspofungin in patients with severe hepatic dysfunction (Child Pugh score 7 to 9), but is not required for micafungin or anidulafungin. 6.3. Adverse Effects All three echinocandins were well tolerated in Phase II/III clinical trials, with the most common adverse effects being phlebitis/venous irritation, headache, fever, and rash. Infusion-related reactions analogous to the “red person’s syndrome” observed with vancomycin infusions have been described with all three echinocandins due to histamine release during infusions. The most common adverse effects reported with echinocandin therapy are venous irritation when infused through a peripheral vein and transient abnormalities in hepatic transaminases and bilirubin. The echinocandins are neither substrates nor inhibitors of cytochrome P450 enzymes of P-glycoprotein enzymes. For reasons not completely understood, coadministration of caspofungin with inducers of P450 3A4 (e.g., rifampin, phenytoin) results in modest (25% to 50%) decrease in the area under the curve (AUC), which can be overcome with higher dosages. P450 inducers do not appear to have as pronounced effect on the clearance of micafungin or anidulafungin. Caspofungin modestly (∼20%) decreases the AUC of concomitant tacrolimus therapy. Micafungin modestly increases the AUC of nifedipine and sirolimus. No clinically significant drug interactions have been identified thus far for anidulafungin. 7. FLUOROPYRIMIDINES Flucytosine (5-fluorocytosine, 5-FC) is the only agent among the fluoropyrimidine class of antifungal agents approved for the treatment of invasive fungal infections. In 130 Russell E. Lewis and Annette W. Fothergill the United States it is available only in oral capsule formulation. The usefulness of flucytosine for treating invasive mycoses is hampered by its relatively narrow spectrum, high rates of acquired resistance among common pathogens (i.e., Candida species), and significant potential for toxic effects. For these reasons, flucytosine is not used as monotherapy and has a minimal role in the treatment of most mycoses. 7.1. Spectrum and Susceptibility 5-Fluorocytosine has activity against both Candida and Cryptococcus species and is not recommended for the treatment of infections caused by other fungal species. The rate of resistance against Candida species is expected in about 5% of isolates while for Cryptococcus species resistance occurs in about 2% of isolates tested. 7.2. Pharmacokinetics Because flucytosine widely distributes throughout the body, including the CSF, after oral administration, it is a useful adjuvant agent for difficult to treat infections in these anatomically restricted sites. Several randomized prospective studies of cryptococcal meningitis in patients with AIDS have shown that the addition of flucytosine to amphotericin B therapy results in more rapid sterilization of the CSF, decreased early mortality, and fewer relapses after completion of “induction” antifungal therapy. 7.3. Adverse Effects Flucytosine was originally developed as an antitumor chemotherapy before it was discovered to have antifungal activity against common yeasts. Not surprisingly, the most common side effects are nausea and vomiting, increases in serum transaminases, and bone marrow suppression. The risk of bone marrow suppression can be reduced if serum levels are maintained at less than 100 μg/ml. Because flucytosine is eliminated unchanged through the kidney, serum level monitoring and dosage adjustments are required in patients receiving flucytosine in combination with amphotericin B or other nephrotoxic agents. Gastrointestinal side effects are seen in up to 6% patients receiving oral flucy- tosine including diarrhea, nausea, and vomiting. Reversible elevations in hepatic serum transmaninases and alkaline phosphatase have also been reported in 4% to 10% of patients receiving flucytosine. The most serious toxicity associated with flucytosine, however, is bone marrow suppression, which occurs in 6% of patients. Some evidence has accumulated in the last two decades that marrow toxicity is enhanced if serum concentrations of flucytosine exceed 100 μg/ml. 8. COMBINATION ANTIFUNGAL THERAPY Because of their unique mechanism of action, the introduction of the echinocandins has renewed interest in the use of combination antifungal therapy for invasive mycoses. The most common reasons for consideration of combination therapy are to (1) broaden the spectrum of antifungal coverage of opportunistic mycoses; particularly in severely immunocompromised patients; (2) to enhance the activity of an antifungal regimen through (presumably) synergistic antifungal effects, especially in severely immunocom- promised patients with progressive disease; and (3) to overcome the pharmacokinetic 6. Antifungal Agents 131 limitations of a single antifungal agent in the treatment of life-threatening mycoses in an anatomically restricted sites such as the CNS (e.g., combined use of flucytosine and amphotericin B for cryptococcal meningitis) (37). 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Antimicrob Agents Chemother 2002;46:828–833. 30. Imhof A, Walter RB, Schaffner A. Continuous infusion of escalated doses of amphotericin B deoxycholate: An open-label observational study. Clin Infect Dis 2003;36:943–951. 31. Eriksson U, Seifert B, Schaffner A. Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial. Br Med J 2001;322:579–582. 32. Pfaller MA, Messer SA, Hollis RJ, et al. Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States. Diagn Microbiol Infect Dis 1999;33:217–222. 33. Lewis RE. Pharmacotherapy of Candida bloodstream infections: new treatment options, new era. Expert Opin Pharmacother 2002;3:1039–1057. 34. Johnson LB, Kauffman CA. Voriconazole: a new triazole antifungal agent. Clin Infect Dis 2003;36:630–637. 35. Ezzet F, Wexler D, Courtney R, Krishna G, Lim J, Laughlin M. Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations. Clin Pharmacokinet 2005;44:211–220. 6. Antifungal Agents 133 36. Marr KA, Leisenring W, Crippa F, et al. Cyclophosphamide metabolism is affected by azole antifungals. Blood 2004;103:1557–1559. 37. Kontoyiannis DP, Lewis RE. Toward more effective antifungal therapy: the prospects of combination therapy. Br J Haematol 2004;126:165–175. SUGGESTED READINGS Boucher HW, Groll AH, Chiou CC, Walsh TJ. Newer systemic antifungal agents: pharmacok- ientics, safety and efficacy. Drugs 2004:64:1997–2020. Rex JH, Pfaller MA. Has antifungal susceptibility testing come of age? Clin Infect Dis 2002;35:982–989. Sheehan DJ, Hitchcock CA, Sibley CM. Current and emerging azole antifungal agents. Clin Microbiol Rev 1999;12:40–79. Gonzales GM, Fothergill AW, Sutton DA, Rinaldi MG, Lobenberg D. In vitro activities of new and established triazoles against opportunistic filamentous and dimorphic fungi. Med Mycol 2005;43:281–284. IV Mycoses 7 Candidiasis Jack D. Sobel, MD 1. INTRODUCTION Candida species are ubiquitous fungi and the most common fungal pathogens affecting humans (1,2). The growing problem of mucosal and systemic candidiasis reflects the enormous increase in the pool of patients at risk and the increased oppor- tunity for Candida to invade tissues normally resistant to invasion. Candida are true opportunistic pathogens that exploit recent technological advances to gain access to the vascular circulation and deep tissues. Candida in particular affects high-risk patients who are either immunocompromised or critically ill. 2. ETIOLOGIC AGENTS Candida are yeast-like fungi that can form true hyphae and pseudohyphae. These yeasts are typically confined to human and animal reservoirs; however, they are frequently recovered from the hospital environment, including from food, countertops, air conditioning vents, floors, respirators, and medical personnel. They are also normal commensals of diseased skin and mucosal surfaces of the gastrointestinal (GI), genitourinary, and respiratory tracts. More than 100 species of Candida exist, but only a few are recognized as causing disease in humans (1). The medically significant Candida species are shown in Table 7.1. Candida glabrata and Candida albicans account for 70% to 80% of yeasts isolated from patients with invasive candidiasis. C. glabrata has become important because of its increasing worldwide incidence and because it is intrinsically less suscep- tible to azoles and amphotericin B. Two uncommon Candida species, C. lusitaniae and C. guilliermondii, are important because of their innate resistance to amphotericin B. C. krusei; although not as common as some Candida species, is clinically significant because of its intrinsic resistance to fluconazole and decreased susceptibility to all other antifungals, including amphotericin B (Table 7.1) (3). From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 137 Table 7.1 General patterns of susceptibility of Candida species Fluconazole Itraconazole Flucytosine Amphotericin B Voriconazole Echinocandinsa Candida species C. albicans S S S S S S C. tropicalis S S S S S S C. parapsilosis S S S S S S (to I?) C. glabrata S-DD to R S-DD to R S S-I S to I S C. krusei R S-DD to R I-R S-I S to I S C. lusitaniae S S S S to R S to I S C. Kefyr S S S S S S C. guilliermondii S S S S to R S S C. dubliniensis S S S S S S S, susceptible; R, resistant; S-DD, susceptible-dose dependent. aSusceptibility methods for the echinocandin antifungal agents (caspofungin, micafungin, and anidulafungin) are not standardized, and interpretive criteria are not available. All three drugs show generally similar susceptibility patterns and therefore are shown as a class. 7. Candidiasis 139 3. EPIDEMIOLOGY Candida species are the most common cause of fungal infection, primarily affecting immunocompromised patients (4–7). Oropharyngeal colonization is found in 30% to 55% of healthy young adults, and Candida may be detected in 40% to 65% of normal fecal flora. Clinical and autopsy studies have confirmed the marked increase in the incidence of disseminated candidiasis, reflecting a parallel increase in the frequency of candidemia. This increase is multifactorial in origin, reflecting an increased recognition as well as a growing population of patients at risk (i.e., patients undergoing complex surgical procedures and those with indwelling vascular devices). The increase in disseminated candidiasis also reflects the improved survival of patients with underlying neoplasms, collagen vascular disease, and immunosuppression. Candidiasis causes more fatalities than any other systemic mycosis. Early studies observed that in febrile neutropenic patients who die of sepsis, there was a 20% to 40% chance of finding evidence of invasive candidiasis at autopsy. Bodey described 21% of fatal infections in leukemic patients as the result of invasive fungal disease, in contrast with 13% and 6% of fatal infections in patients with lymphoma and solid tumors, respectively (8). Systemic candidiasis has been described in 20% to 30% of patients undergoing bone marrow transplantation. Candida species are now the fourth most commonly isolated pathogens from blood cultures in hospitals (4–7). A dramatic increase in the incidence of candidemia has occurred in the last four decades. Epidemiologic data indicate that at least 10% to 12% of all nosocomial infections and 8% to 15% of all nosocomial bloodstream infections are caused by Candida. Candidemia and disseminated candidiasis mortality rates have not improved markedly over the past few years and remain in the 30% to 40% range, resulting in a serious economic impact (9). Candidemia is associated with considerable prolongation of the length of hospital stay (70 days versus 40 days in matched patients) (10,11). Although mucocutaneous fungal infections such as oral thrush and Candida esophagitis are common in acquired immunodeficiency syndrome (AIDS) patients, candidemia and disseminated candidiasis are not. Within the hospital setting, areas with the highest rates of candidemia include intensive care units (ICUs), surgical units, trauma units, and neonatal ICUs. In fact, 25% to 50% of all nosocomial candidemia occurs in critical care units. Neutropenic patients, formerly the highest risk group, are no longer the most vulnerable subpopulation, likely as a result of the widespread use of fluconazole prophylaxis during neutropenia (12). In some tertiary care centers, C. albicans is no longer the most frequent bloodstream isolate, having been replaced by C. glabrata, which has replaced C. tropicalis as the most prevalent non-albicans species, now causing 3% to 35% of all candidemias. Non-albicans Candida have also become an increasing problem in ICUs, attributed to the more widespread use of fluconazole in this population (13). Risk factors for Candida bloodstream infections include broad-spectrum antibiotic use, chemotherapy, corticosteroids, intravascular catheters, receipt of total parenteral nutrition (TPN), recent surgery, hospitalization in ICU, malignancy, neutropenia, and fungal colonization. The most important risk factor for invasive candidiasis is a prolonged stay in the ICU (11). 140 Jack D. Sobel 4. PATHOGENESIS AND IMMUNOLOGY Host defects play a significant role in the development of candidal infections (1). The intact skin constitutes a highly effective, impermeable barrier to Candida penetration. Disruption of the skin from burns, wounds, and ulceration permits invasion by colonizing opportunistic organisms. Similarly, indwelling intravascular devices provide an efficient conduit that bypasses the skin barrier. The major defense mecha- nisms operating at the mucosal level to maintain colonization and prevent invasion include normal protective bacterial flora and cell-mediated immunity. The impor- tance of the latter mechanism is highlighted by chronic mucocutaneous candidiasis, a congenital Candida antigen-specific deficiency manifested by chronic, intractable, and severe mucocutaneous infection. However, candidemia and disseminated candidiasis are rare in the presence of an intact humoral and phagocytic system. An effective phagocytic system is the critical defense mechanism that prevents Candida deep tissue invasion, thereby limiting candidemia and preventing dissemi- nation. Polymorphonuclear and monocytic cells are capable of ingesting and killing blastoconidia and hyphal phases of Candida, a process that is enhanced by serum complement and specific immunoglobulins. Severe leukocyte qualitative dysfunction (e.g., chronic granulomatous disease) is associated with disseminated, often life- threatening candidal infections. Myeloperoxidase deficiency also results in increased susceptibility to invasive infection. Several Candida virulence factors contribute to their ability to cause infection, including surface molecules that permit adherence of the organism to other structures (human cells, extracellular matrix, prosthetic devices), acid proteases, phospholipase, and the ability to convert from yeast to hyphal form. Candidal colonization is at the highest levels in patients at the extremes of age—neonates and adults older than 65 years. Numerous risk factors are associated with increased colonization. Once the colonized mucosal surface is disrupted by chemotherapy or trauma, organisms penetrate the injured areas and gain access to the bloodstream. Although the yeast phase of Candida is capable of penetrating intact mucosal cells, the more virulent hyphal phase is more often associated with tissue invasion. Indwelling central venous catheters appear to be a frequent route of bloodstream invasion, accounting for at least 20% of candidemias. Hyperalimentation (TPN) constitutes an independent risk factor. The risk of fungemia is increased with prolonged duration of catheterization, which also increases the risk of local phlebitis, occasionally progressing to suppurative thrombosis. Tunneled catheters (e.g., Hickman and Broviac) are less commonly the source of candidemia, but the intravascular portion may become colonized and infected as the result of candidemia originating from a second independent focus or portal of entry. Fungal invasion from colonized wounds occurs rarely, except in patients with extensive burns. Similarly, the respiratory tract, although frequently colonized, is not a common site for Candida invasion and rarely is a source of dissemination. After invasion of the bloodstream, efficient phagocytic cell function rapidly clears the invading organisms, especially when the inoculum is small. More prolonged candidemia is likely in granulocytopenic patients, especially when diagnosis and 7. Candidiasis 141 treatment are delayed. This results in increased risk of hematogenous spread and metastatic seeding of multiple visceral sites, primarily the kidney, eyes, liver, skin, and central nervous system. Manifestations of metastatic infection may be apparent immediately or may be delayed several weeks or even months, long after predisposing factors (e.g., granulocytopenia) have resolved. A third route for bloodstream invasion is persorption via the GI wall, following massive colonization with a high titer of organisms that pass directly into the blood- stream. Candidemia and disseminated candidiasis almost invariably follow serious bacterial infections, especially bacteremia. 5. CLINICAL MANIFESTATION Candida infections can present in a wide spectrum of clinical syndromes, depending on the site of infection and the degree of immunosuppression of the host. 5.1. Cutaneous Candidiasis Syndromes Generalized cutaneous candidiasis manifests as a diffuse eruption over the trunk, thorax, and extremities. Patients have a history of generalized pruritus with increased severity in the genitocrural folds, anal region, axillae, hands, and feet. Physical exami- nation reveals a widespread rash that begins as individual vesicles and spreads into large confluent areas. Intertrigo affects any site where skin surfaces are in close proximity, providing a warm, moist environment. A red pruritic rash develops,

beginning with vesiculo- pustules, enlarging to bullae, which then rupture causing maceration and fissuring. The area involved typically has a scalloped border, with a white rim consisting of necrotic epidermis that surrounds the erythematous macerated base. Satellite lesions are frequently found. These may coalesce and extend into larger lesions. Candida folli- culitis is predominantly found in hair follicles and rarely becomes extensive. Paronychia and onychomycosis are frequently associated with immersion of the hands in water, especially in patients with diabetes mellitus. These patients usually have a history of a painful and erythematous area around and underneath the nails and nail beds. Chronic mucocutaneous candidiasis describes a unique group of individuals with Candida infections of the skin, hair, nails, and mucous membranes that tend to have a protracted and persistent course. Most infections begin in infancy or the first two decades of life; whereas onset in people older than 30 years is rare. These chronic and recurrent infections frequently result in a disfiguring form called Candida granuloma. Most patients survive for long periods and rarely experience disseminated fungal infections. Chronic mucocutaneous candidiasis is frequently associated with multiple endocrinopathies. Examination reveals disfiguring lesions of the face, scalp, hands, and nails occasionally associated with oral thrush and vitiligo. 5.2. Oropharyngeal Candidiasis Oropharyngeal candidiasis (OPC) occurs in association with serious underlying conditions such as diabetes, leukemia, neoplasia, corticosteroid use, antimicrobial therapy, radiation therapy, dentures, and human immunodeficiency virus (HIV) infection. Persistent OPC in infants may be the first manifestation of childhood AIDS or 142 Jack D. Sobel chronic mucocutaneous candidiasis. Samonis et al. reported that 28% of cancer patients not receiving antifungal prophylaxis developed OPC (14). In a similar immunocom- promised, hospitalized population, Yeo et al. observed OPC in 57% of patients (15). Approximately 80% to 90% of patients with HIV infection will develop OPC at some stage of their disease. The presence of OPC should alert the physician to the possibility of underlying HIV infection. Untreated, 60% of HIV-infected patients develop an AIDS-related infection or Kaposi’s sarcoma within 2 years of the appearance of OPC. Many HIV-positive patients experience recurrent episodes of OPC and esophageal candidiasis as HIV progresses, and multiple courses of antifungals administered may contribute to the development of antifungal resistance. Antifungal agents are less effective and take longer to achieve a clinical response in HIV-positive patients than in cancer patients. There has been a significant increase in the incidence of non-albicans Candida recovered from HIV-positive patients. C. albicans remains the most common species responsible for OPC (80% to 90%). C. albicans adheres better in vitro to epithelial cells than non-albicans Candida does. The manifestations of OPC (commonly called thrush) vary significantly, from none to a sore, painful mouth, burning tongue, and dysphagia. Frequently, patients with severe objective (examination) changes are asymptomatic. Clinical signs include a diffuse erythema with white patches (pseudomembranes) that appear as discrete lesions on the surfaces of the mucosa, throat, tongue, and gums. With some difficulty, the plaques can be wiped off, revealing a raw, erythematous, and sometimes bleeding base. OPC impairs quality of life and results in a reduction in fluid or food intake. The most serious complication of untreated OPC is extension to the esophagus. Fungemia and disseminated candidiasis are uncommon. Chronic atrophic stomatitis or denture stomatitis is a very common form of OPC, with soreness and burning of the mouth. Characteristic signs are chronic erythema and edema of the portion of the palate that comes into contact with dentures. Denture stomatitis is found in 24% to 60% of denture wearers and is more frequent in women than in men. Notably, C. glabrata has been identified in 15% to 30% of all cultures, a higher prevalence than generally found in the mouth. Angular cheilitis (perlèche), also called cheilosis, is characterized by soreness, erythema, and fissuring at the corners of the mouth. Chronic hyperplastic candidiasis (Candida leukoplakia) produces oral white patches, or leukoplakia, which are discrete, transparent-to-whitish, raised lesions of variable sizes found on the inner surface of the cheeks and, less frequently, on the tongue. Midline glossitis (median rhomboid glossitis, acute atrophic stomatitis) refers to symmetrical lesions of the center dorsum of the tongue characterized by loss of papillae and erythema. 5.3. Esophageal Candidiasis Candida esophagitis occurs in predisposed individuals. C. albicans is the most common cause. The prevalence of Candida esophagitis has increased because of AIDS and the increased numbers of transplant, cancer, and severely immunocompromised patients. Esophageal candidiasis in an HIV-infected patient may be the first manifes- tation of AIDS. Candida esophagitis tends to occur later in the natural history 7. Candidiasis 143 of HIV infection and almost invariably at a much lower CD4 count. In cancer patients, factors predisposing to esophagitis include recent exposure to radiation, cytotoxic chemotherapy, antibiotic and corticosteroid therapy, and neutropenia. Clinical features include dysphagia, odynophagia, and retrosternal pain. Constitutional findings, including fever, occur only occasionally. Rarely, epigastric pain is the dominant symptom. Although esophagitis may occur as an extension of OPC, in more than two thirds of published reports, the esophagus was the only site involved; more often infection involved the distal two thirds of the esophagus. Candida esophagitis in AIDS patients may occur in the absence of symptoms despite extensive objective esophageal involvement. Kodsi classified Candida esophagitis on the basis of its endoscopic appearance (16). Type I cases refer to a few white or beige plaques up to 2 mm in diameter. Type II plaques are larger and more numerous. In the milder grades, plaques may be hyperemic or edematous, but there is no ulceration. Type III plaques may be confluent, linear, nodular, and elevated, with hyperemia and frank ulceration, and type IV plaques additionally have increased friability of the mucosa and occasional narrowing of the lumen. Uncommon complications of esophagitis include perforation, aortic–esophageal fistula formation, and rarely, candidemia or bacteremia. A reliable diagnosis can be made only by histologic evidence of tissue invasion in biopsy material. Nevertheless, antifungal therapy is frequently initiated empirically with minimal criteria in a high-risk patient. The mere presence of Candida within an esophageal lesion as established by brushings, smear, or culture does not provide suffi- cient evidence to distinguish Candida as a commensal from Candida as the responsible invasive pathogen. Radiographic studies have been replaced by endoscopy, which not only provides a rapid and highly sensitive diagnosis, but also is the only reliable method of differ- entiating among the various causes of esophagitis. The characteristic endoscopic appearance is described as yellow-white plaques on an erythematous background, with varying degrees of ulceration. Differential diagnosis includes radiation esophagitis, reflux esophagitis, cytomegalovirus, or herpes simplex virus infection. In AIDS patients, it is not uncommon to identify more than one etiologic agent causing esophagitis. 5.4. Respiratory Tract Candidiasis Laryngeal candidiasis is seen primarily in HIV-infected patients and occasionally in those with hematologic malignancies. The patient presents with a sore throat and hoarseness and the diagnosis is made by direct or indirect laryngoscopy. Candida tracheobronchitis is a rare form of candidiasis seen in HIV-positive or severely immunocompromised subjects complaining of fever, productive cough, and shortness of breath. Physical examination reveals dyspnea and scattered rhonchi. The diagnosis generally is made during bronchoscopy. Candida pneumonia is also a rare form of candidiasis. The most common form of infection appears to be multiple lung abscesses due to the hematogenous dissem- ination of Candida. As there may be a high degree of colonization and isolation of Candida from the upper respiratory tract, diagnosis requires the visualization of Candida invasion on histopathology. Patient history usually reveals similar risk factors 144 Jack D. Sobel for disseminated candidiasis, and patients complain of shortness of breath, cough, and fever. Sputum or endotracheal secretions positive for Candida usually indicate upper respiratory tract colonization and have low predictive value for pneumonia. 5.5. Vulvovaginal Candidiasis In the United States, Candida vaginitis is the second most common vaginal infection. During the childbearing years, 75% of women experience at least one episode of vulvovaginal candidiasis (VVC), and 40% to 50% of these women experience a second episode. A small subpopulation of women experiences repeated, recurrent episodes of Candida vaginitis. Candida may be isolated from the genital tract of about 10% to 20% of asymptomatic, healthy women of childbearing age. Candida vaginitis can be classified as complicated or uncomplicated, depending on factors such as severity and frequency of infection and the causative Candida species (Table 7.2). Increased rates of asymptomatic vaginal colonization with Candida and Candida vaginitis are seen in pregnancy (30% to 40%), with the use of oral contraceptives with a high estrogen content, and in uncontrolled diabetes mellitus. The hormonal dependence of the infection is illustrated by the fact that Candida is seldom isolated from premenarchal girls, and the prevalence of Candida vaginitis is lower after menopause, except in women taking hormone replacement therapy (HRT). Other factors include corticosteroid and antimicrobial therapy, the use of an intrauterine device, high frequency of coitus, and refined-sugar eating binges. Vulvar pruritus is the most common symptom of VVC and is present in most symptomatic patients. Vaginal discharge is often minimal and occasionally absent. Although described as being typically “cottage cheese-like” in character, the discharge may vary from watery to homogeneously thick. Vaginal soreness, irritation, vulvar burning, dyspareunia, and external dysuria are common. Malodorous discharge is characteristically absent. Typically, symptoms are exacerbated during the week before menses, while the onset of menstrual flow frequently brings some relief. Examination reveals erythema and swelling of the labia and vulva, often with discrete pustulopapular peripheral lesions. The cervix is normal. Vaginal mucosal erythema with adherent whitish discharge is typically present. In most symptomatic patients, VVC is readily diagnosed by microscopic examination of vaginal secretions. A wet mount of saline preparation has a sensitivity of only 40% to 60%. A 10% potassium hydroxide preparation (KOH) is more sensitive in diagnosing the presence of budding yeast. Patients with Candida vaginitis have a normal vaginal Table 7.2 Classification of Candida vaginitis Uncomplicated (90%) Complicated (10%) Severity Mild or moderate Severe Frequency Sporadic Recurrent Organism Candida albicans Non-albicans species of Candida Host Normal Abnormal (e.g., uncontrolled diabetes mellitus) 7. Candidiasis 145 pH (4.0 to 4.5). A pH of more than 4.5 suggests bacterial vaginosis, trichomoniasis, or mixed infection. Routine cultures are unnecessary, but in suspicious cases with negative microscopy cases vaginal culture should be performed. Although vaginal culture is the most sensitive method available for detecting Candida, a positive culture does not necessarily indicate that Candida is responsible for the vaginal symptoms. 5.6. Urinary Tract Candidiasis Candiduria is rare in otherwise healthy people. Although epidemiologic studies have documented candiduria in approximately 10% of individuals sampled, many of these culture results reverted to negative when a clean-catch technique was used. The incidence of fungal urinary tract infections (UTIs), specifically candiduria, has dramatically increased recently, especially among patients with indwelling urinary catheters. Platt et al. reported that 26.5% of all urinary tract infections related to indwelling catheters were caused by fungi. Candida are the organisms most frequently isolated from the urine samples of patients in surgical ICUs and 10% to 15% of nosocomial UTIs are caused by Candida (17). Diabetes mellitus may predispose patients to candiduria by enhancing Candida colonization of the vulvovestibular area (in women), by enhancing urinary fungal growth in the presence of glycosuria, by lowering host resistance to invasion by fungi as a consequence of impaired phagocytic activity, and by promoting stasis of urine in those with neurogenic bladder. Antibiotics also increase colonization of the GI tract by Candida, which are normally present in approximately 30% of immunocompetent adults. In patients receiving antibi- otics, colonization rates approach 100%. Candiduria is almost invariably preceded by bacteriuria. Indwelling urinary catheters serve as a portal of entry for microorganisms into the urinary drainage system. Other risk factors include the extremes of age, female sex, use of immunosuppressive agents, venous catheters, interruption of urine flow, radiation therapy, and genitourinary tuberculosis. In a large multicenter study by Kauffman et al., C. albicans was found in 51.8% of 861 patients with funguria. The second most common pathogen (134 patients) was C. glabrata (18). Other non-albicans Candida are also very common and far more prevalent than in other sites (i.e., oropharynx and vagina), possibly as a function of urine composition and pH selectivity for non-albicans species. In approximately 10% of patients, more than one species of Candida are found simultaneously. Ascending infection is

by far the most common route for infection of the bladder. It occurs more often in women because of a shorter urethra and frequent vulvovestibular colonization with Candida (10% to 35%). Ascending infection that originates in the bladder can infrequently lead to infection of the upper urinary tract, especially if vesicoureteral reflux or obstruction of urinary flow occurs. This may eventually result in acute pyelonephritis and, rarely, candidemia. A fungus ball consisting of yeast, hyphal elements, epithelial and inflammatory cells, and, sometimes, renal medullary tissue secondary to papillary necrosis may complicate ascending or descending infections. Hematogenous spread is the most common route for renal infection (i.e., renal candidiasis). Candida have a tropism for the kidneys; one study revealed that 90% 146 Jack D. Sobel of patients with fatal disseminated candidiasis had renal involvement at autopsy. Frequently, when renal candidiasis is suspected, blood cultures are no longer positive. The finding of Candida organisms in the urine may represent contamination, colonization of the drainage device, or infection. Contamination of a urine specimen is common, especially with suboptimal urine collection from a catheterized patient or from a woman who has heavy yeast colonization of the vulvovestibular area. Given the capacity of yeast to grow in urine, small numbers of yeast cells that migrate into the collected urine sample may multiply quickly. Therefore, high colony counts could be the result of yeast contamination or colonization. Colonization usually refers to the asymptomatic adherence and settlement of yeast, usually on drainage catheters or other foreign bodies in the urinary tract (i.e., stents and nephrostomy tubes), and it may result in a high concentration of the organisms on urine culture. Simply culturing the organism does not imply clinical significance, regardless of the concentration of organisms in the urine. Accordingly, some clinicians require confirmation of Candida presence by a second urine sample examination before they initiate treatment or further investigation. Infection is caused by superficial or deep tissue invasion. Kozinn showed that colony counts of greater than 104 colony-forming units (cfu)/ml of urine were associated with infection in patients without indwelling urinary catheters, although clinically significant renal candidiasis has been reported with colony counts of 103 cfu/ml of urine (19). Pyuria supports the diagnosis of infection in patients with a urinary catheter but can result from mechanical injury of the bladder mucosa by the catheter or from coexistent bacteriuria. In summary, absence of pyuria and low colony counts tend to rule out Candida infection, but the low specificity of pyuria and counts greater than 103 cfu/ml require that results be interpreted in their clinical context. The number of yeast cells in urine has little value in localizing the anatomical level of infection. Rarely, a granular cast containing Candida hyphal elements is found in urine, allowing localization of the infection to the renal parenchyma. Declining renal function suggests urinary obstruction or renal invasion. For candiduria patients with sepsis, is it not only necessary to obtain blood cultures, but also, given the frequency with which obstruction and stasis coexist, essential to perform radiographic visualization of the upper tract. Any febrile patient for whom therapy for candiduria is considered necessary should be investigated for the anatomic source of candiduria. In contrast, patients without sepsis require no additional studies unless candiduria persists after the removal of catheters. Candiduria is most often asymptomatic, usually in hospitalized or nursing home patients with indwelling catheters. These patients usually show none of the signs or symptoms associated with UTI. Symptomatic Candida cystitis is uncommon. Cystoscopy, although rarely indicated, reveals soft, pearly white, elevated patches with friable mucosa underneath and hyperemia of the bladder mucosa. Emphysematous cystitis is a rare complication of lower UTI, as is prostatic abscess. Upper UTIs present with fever, leukocytosis, and costovertebral angle tenderness, indistinguishable from bacterial pyelonephritis and urosepsis. Ascending infection almost invariably occurs in the presence of urinary obstruction and stasis, especially in patients with diabetes or nephrolithiasis. 7. Candidiasis 147 A major complication of upper UTI is obstruction caused by fungus balls (bezoars), which can be visualized on ultrasonography. Renal colic may occur with the passage of fungal “stones,” which are actually portions of these fungus balls. Patients with hematogenous seeding of the kidneys caused by candidemia may present with high fever, hemodynamic instability, and variable renal insufficiency. Blood culture results are positive for Candida in half of these patients. Retinal or skin involvement may suggest dissemination, but candiduria and a decline in renal function are often the only clues to systemic candidiasis in a febrile, high-risk patient. 5.7. Abdominal Candidiasis, Including Peritonitis Candida infection has been increasingly recognized as a cause of abdominal sepsis and is associated with a high mortality. Peritoneal contamination with Candida follows either spontaneous GI perforation or surgical opening of the gut. However, after contaminating the peritoneal cavity, Candida organisms do not inevitably result in peritonitis and clinical infection. Risk factors for peritonitis, include recent or concomitant antimicrobial therapy, inoculum size, and acute pancreatitis. Translocation of Candida across the intact intestinal mucosa has been shown experimentally in animals and in a volunteer. Additional risk factors for invasive candidiasis include diabetes, malnutrition, ischemia, hyperalimentation, neoplasia, and multiple abdominal surgeries. Pancreatic transplantation, especially with enteric drainage, is associated with intraabdominal Candida abscess formation. Candida have a unique affinity for the inflamed pancreas, resulting in intrapancreatic abscesses or infecting accompa- nying pseudocysts. In Candida peritonitis, Candida usually remains localized to the peritoneal cavity, with the incidence of dissemination at about 25%. The clinical significance of Candida isolated from the peritoneal cavity during or after surgery has been controversial. Several earlier studies concluded that a positive culture did not require antifungal therapy. Calandra et al., in a review of Candida isolates from the peritoneal cavity, determined that Candida caused intraabdominal infection in 19 of 49 (39%) patients (20). In 61% of patients, Candida isolation occurred without signs of peritonitis. Accordingly, in each patient, clinicians should consider the clinical signs of infection and other risk factors when deciding whether to initiate antifungal therapy (21). Candida peritonitis as a complication of continuous ambulatory peritoneal dialysis (CAPD) is more common, but it infrequently results in positive blood cultures or hematogenous dissemination. In a series of CAPD patients followed for 5 years, fungal peritonitis, most commonly due to Candida, accounted for 7% of episodes of peritonitis. Seventeen cases of fungal peritonitis were reported, with eight associated deaths. Few risk factors have emerged except for recent hospitalization, previous episodes of peritonitis, and antibacterial therapy. Clinically, fungal peritonitis cannot be differentiated from bacterial peritonitis except by Gram stain and culture of dialysate. Yeast in the bile is not uncommon, especially after biliary surgery, and has the same significance as asymptomatic bactibilia (i.e., colonization only); however Candida is an infrequent cause of cholecystitis and cholangitis. Other risk factors include diabetes, immunosuppression, abdominal malignancy, and the use of biliary stents. 148 Jack D. Sobel Biliary infection is usually polymicrobial, and when isolated, Candida is a pathogen that should not be ignored. 5.8. Candida Osteomyelitis and Arthritis Although previously rare, Candida osteomyelitis is now not uncommon, usually as the result of hematogenous dissemination, with seeding of long bones in children and the axial skeleton in adults. Sites of bone infection include the spine (vertebral and intravertebral disk), wrist, femur, humerus, and costochondral junctions. Osteomyelitis may present weeks or months after the causal candidemic episode; therefore, at presentation, blood cultures are usually negative and radiologic findings nonspecific. A bone biopsy is usually required for diagnosis . Occasionally, postoperative wound infections may spread to contiguous bone such as the sternum and vertebrae. Regardless of the source, manifestations resemble bacterial infection but run a more insidious course, with a significant delay in diagnosis. Candida arthritis generally represents a complication of hematogenous candidiasis and rarely follows local trauma, surgery, or intra-articular injections. Patients with underlying joint disease (e.g., rheumatoid arthritis, prosthetic joints) are at increased risk. Candida arthritis can occur in any joint, is usually monoarticular (knee), but has been reported to affect multiple joints in up to 25% of cases. Infection resembles bacterial septic arthritis, but chronic infection often develops with secondary bone involvement because of the delay in diagnosis and suboptimal treatment. 5.9. Candidemia and Disseminated Candidiasis Clinical presentation of candidemia varies from fever alone and absence of any organ-specific manifestations to a wide spectrum of manifestations, including fulminant sepsis (22). Accordingly, acute candidemia is indistinguishable from bacterial sepsis and septic shock. In general, there are no specific clinical features associated with individual Candida species. Candidemia may also present with manifestations of systemic and invasive metastatic candidiasis, although when these occur, blood cultures have frequently become negative. Accordingly, candidemia is a marker, although insensitive, of deep invasive candidiasis. Only 50% of patients with disseminated candidiasis will have positive blood cultures, and an antemortem diagnosis is even lower (15% to 40%). Dissemination to multiple organs may occur with candidemia, especially to the kidney, eye, brain, myocardium, liver, and spleen in leukemia patients, but infection can also involve the lungs, skin, vertebral column, and endocardium. The possibility of asymptomatic disseminated infection drives the treatment principles of candidemia. Transient candidemia can occur from any source but most often follows intravascular catheter infection, with prompt resolution of candidemia following catheter removal. Prolonged candidemia, especially when blood cultures remain persistently positive on appropriate antifungal treatment, suggests a persistent focus or source (e.g., intravascular catheter, abscess, suppurative thrombophlebitis, endocarditis, severe neutropenia) or antifungal resistance, which albeit rare, is more common with some of the non-albicans Candida. When candidemia is diagnosed, a general physical examination rarely reveals clinical signs of dissemination, but a 7. Candidiasis 149 thorough examination, including a dilated funduscopic examination, is mandatory. The crude mortality rate reported in patients with candidemia ranges from 40% to 60%, with an attributable mortality of 38%, exceeding that of most bacteremias. McNeil et al. reported a 50% reduction in national mortality rates for invasive candidiasis since 1989 after a steady increase in mortality in the previous decades, reaching 0.62 death/100,000 population (9). The decrease in mortality, despite increased invasive disease, may be related to increased awareness, earlier diagnosis, and increased therapeutic options, primarily fluconazole and echinocandins. 5.10. Ocular Candidiasis Candida organisms gain access to the eye by one of two routes: direct inoculation during eye surgery or trauma, or as the result of hematogenous spread (endogenous). Once endophthalmitis occurs, therapy, especially if delayed, is often insufficient to prevent blindness. Given the recent increased incidence of nosocomial candidemia, a parallel increase in endophthalmitis has occurred. Endophthalmitis should raise the suspicion of concomitant, widely disseminated candidiasis. Estimates of the incidence of eye involvement during candidemia have been as high as 37%, but recent studies indicate a reduced rate of less than 10%. Only half of patients diagnosed with endoph- thalmitis have a history of recent candidemia. Symptoms of chorioretinitis vary; may be absent in patients too ill to complain; and include visual blurring, floaters, scotomata, and blindness. Funduscopic examination reveals white, cotton ball-like lesions situated in the chorioretinal layer that may progress rapidly to extend into the posterior vitreous. Indirect ophthalmoscopy with pupillary dilation is necessary to achieve complete visualization. To be visible, the lesions require the presence of leukocytes; thus, in the presence of neutropenia, ocular lesions may be absent. 5.11. Cardiac and Endovascular Candidiasis Candida myocarditis is the result of hematogenous dissemination with formation of microabscesses within the myocardium usually detected only on autopsy. Franklin et al. reported that 62% of 50 patients with disseminated candidiasis had myocardial involvement at autopsy (23). Candida may reach the pericardium from adjacent endocarditis or myocarditis, but pericardial involvement is most often the result of hematogenous seeding or direct inoculation during cardiac surgery. Pericarditis is purulent in nature, resembles bacterial infection, and may be complicated by constrictive pericarditis. The advent of prosthetic cardiac valve replacement surgery and the increase in intravenous drug abuse have resulted in a dramatic increase in the incidence of Candida endocarditis, which previously had been rare. Fungal endocarditis is responsible for fewer than 10% of all cases of infective endocarditis. Endocarditis following prosthetic valve surgery (PVE) remains the most common form of Candida endocarditis (>50%). Most episodes occur within 2 months of surgery, although endocarditis can also occur much later (>12 months). Specific risk factors for PVE include complicated surgery, antibiotics, prolonged postoperative use of catheters, and candidemia, even if transient. Non-albicans Candida species are 150

Jack D. Sobel increasingly responsible for prosthetic valve endocarditis, especially C. parapsilosis. Damaged endocardium and prosthetic material, especially suture lines, serve as foci for Candida adherence. Pacemaker-associated endocarditis from Candida has also been reported. Clinical findings and complications in Candida endocarditis are similar to those seen in bacterial endocarditis, with the exceptions of increased frequency of large vegetations and large emboli to major vessels. Aortic and mitral valve involvement is the most common. The higher incidence of embolization is frequently manifested as focal and global neurologic deficits. Some studies have found a reduced incidence of cardiac failure, charging heart murmurs, and splenomegaly. Prosthetic valve endocarditis may recur several years after a putative cure with medical therapy, so long-term follow up is necessary. Most patients with Candida endocarditis have positive blood cultures. Improved diagnosis is the result of greater awareness of the significance of candidemia, newer blood culture techniques, and echocardiography. Visualizing large vegeta- tions via echocardiogram in patients with negative blood culture is strong circum- stantial evidence of Candida endocarditis. Mycologic examination including culture and histopathology should be performed on all surgically removed emboli. Candida endocarditis mortality remains high. Before cardiac surgery was available, mortality exceeded 90%. With combined treatment using surgery and aggressive antifungal therapy, mortality rates of approximately 45% are now typical. Phlebitis due to Candida is common and often associated with subcutaneous catheters. Delay in treatment often results in extensive vascular thrombosis and suppu- ration. Prolonged candidemia, despite adequate antifungal treatment, is not uncommon. Venous thrombi, even after removal of responsible catheters, impair drug penetration and contain persistent microabscesses, with resultant prolonged candidemia. Surgical excision of thrombi is often required in addition to prolonged antifungal therapy. Complications include superior vena cava obstruction, tricuspid valve endocarditis, right-sided mural endocarditis, and pulmonary vein thrombosis. 5.12. Chronic Systemic Candidiasis Hepatosplenic candidiasis (HSC) is a chronic form of disseminated candidiasis that develops as a complication of invasive candidiasis during granulocytopenia. Many now prefer the term chronic systemic candidiasis because other organs (eyes, skin, soft tissue) may also be involved. In the last 2 decades, reports of HSC have increased, probably as a result of improved diagnostic imaging and increased rates of candidemia. Candidemia, although frequently secondary to intravascular catheter infection, generally follows Candida colonization of the gut, together with disruption of the GI mucosa, organism reach the submucosal blood vessels that drain into the portal venous system and into the liver, where focal lesions are established. Thus, many patients with chronic systemic candidiasis have no history of documented candidemia. As patients recover from neutropenia, the lesions that were established during the neutropenic phase become more prominent, especially in the liver, spleen, and kidneys. Clinically, most patients have a history of a hematologic malignancy, cytotoxic chemotherapy, or recent recovery from neutropenia, during which time they were febrile 7. Candidiasis 151 andreceivedantibacterial therapy.Onrecovery fromneutropenia, symptomsofantibiotic- resistant fever and abdominal pain begin and worsen as the neutrophils infiltrate foci of Candida in the liver and spleen. Serum alkaline phosphatase increases, paralleling the increase in leukocytes, although hepatic transaminases are not commonly elevated. 6. DIAGNOSIS In superficial candidiasis, wet mount smears use scrapings or smears from skin, nails, oral or vaginal mucosa examined under the microscope to identify hyphae, pseudohyphae, or budding yeast cells. Potassium hydroxide smear, gram stain, or methylene blue stain may help directly demonstrate fungal cells. For diagnosis of invasive candidiasis, laboratory studies are nonspecific and lack sensitivity. Clinicians are required to act definitively based on a high index of suspicion. In the past, many patients with life-threatening candidiasis died without receiving antifungal therapy. For therapy to be effective, clinicians must act early, often empirically in patients who are febrile and at risk. In candidemia and disseminated candidiasis, blood cultures are helpful, but they are positive in only 40% to 60% of cases of disseminated disease. Urinalysis may be helpful and may be indicative of colonization or renal candidiasis. Non-culture, antigen-based diagnostic assays are not available in the United States. Occasionally, blood cultures obtained via central catheters may indicate contamination. Nevertheless, febrile patients with a single positive blood culture for Candida should always initially be considered to have a proven infection. Given the low sensitivity of blood cultures, as well as the lack of an adequate test for the diagnosis of invasive candidiasis, detection of hematogenous dissemination remains poor. Cultures of nonsterile sites, although not useful in establishing a diagnosis, may demonstrate high degrees of candidal colonization. This may be useful in deciding whether to initiate antifungal therapy in patients with fever unresponsive to broad- spectrum antimicrobials. Positive blood cultures and cultures from sterile sites, on the other hand, are indicative of definite infection using recently established inter- national definitions of the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG). Lesions of HSC may be detected by imaging techniques such as computed tomography (CT) scan, ultrasonography, and magnetic resonance imaging (see Fig. 5.12, Chapter 5). The characteristic “bull’s- eye” lesions seen on ultrasound and/or CT are not detectable until neutrophil recovery. However, the lesions are not specific for HSC. As they resolve during therapy, they may either disappear completely or calcify. Ultrasonography appears to be less sensitive but possibly more specific than CT scanning in demonstrating these lesions. Diagnosis may be confirmed by histopathologic examination and culture of hepatic tissue obtained by either percutaneous biopsy or laparoscopy. The appearance of hyphae in a granulo- matous lesion is itself not specific for Candida and may be caused by other fungi such as Trichosporon, Fusarium, and Aspergillus. In addition, metastatic tumors may simulate the appearance of HSC. Diagnosis of Candida endophthalmitis is usually made on the basis of clinical context and characteristic funduscopic picture. Aspiration of the anterior chamber is justified, but often culture-negative; vitrectomy is often helpful. Polymerase chain reaction (PCR) studies on the aspirate may prove the presence of Candida. 152 Jack D. Sobel Species identification of Candida is critically important because of the increase in non-albicans Candida infections. CHROMagar Candida media allows for the presumptive identification of several Candida species by using enzymatic reactions in specialized media that produce differing colony colors. Several biochemical assays, usually based on fermentation reactions, can be used to identify the different Candida species with more accuracy. Assays that evaluate the assimilation of a number of carbon substrates and generate profiles are used in the identification of different fungal species. Recently, a new sensitive commercial test for diagnosis of fungal infection has been introduced. The Fungitell™ assay measures the amount of -d-glucan released from the fungal cell wall. Sensitivity for Candida infections of greater than 80% has been reported. The test often provides a positive test days before clinical signs and symptoms appear, allowing earlier initiation of therapy (24). The CLSI (formerly NCCLS) microbroth dilution methodology has standardized antifungal susceptibility testing for Candida species. Although not used as a standard of care, it may be helpful in guiding difficult therapeutic decisions. Most of these difficult decisions involve antifungal therapy of refractory oral or esophageal candidiasis in patients with AIDS or of patients with persistent candidemia, including infective endocarditis. 7. TREATMENT Treatment of Candida infections varies considerably and is based on the anatomic location of the infection, the patient’s underlying disease and immune status, the patient’s risk factors for infection as well as the species of Candida responsible for infection, and, in some cases, the susceptibility of the strain to antifungal drugs (Tables 7.1, 7.3, 7.4, and 7.5). In 2004, the Infectious Diseases Society of America published updated practice guidelines for the treatment of candidiasis (26). Azoles have become the mainstay of therapy, including many topical and systemic agents. Polyenes include amphotericin B, lipid-based amphotericin B formulations, and Table 7.3 In vitro susceptibility of Candida species to azoles antifungal agentsa Fluconazole Voriconazole Itraconazole Posaconazole Candida species (MIC50) (MIC50) (MIC50) (MIC50) C. albicans 1 006 05 013 C. tropicalis 1 2 1 1 C. glabrata 16 05 025 1 C. parapsilosis 1 006 013 013 C. krusei 64 1 05 05 C. lusitaniae 2 006 025 013 MIC50, median minimum inhibitory concentration (μg/ml). aBased on 2047 blood culture isolates collected from January 1997 through December 2000. Suscep- tibilities were calculated on the basis of NCCLS methodology. Pfaller et al.(25). 7. Candidiasis 153 Table 7.4 In vitro susceptibility of Candida species to other antifungal agentsa Amphotericin Bb Flucytosineb Caspofunginc Anidulafunginc Micafunginc Candida (MIC50) (MIC50) (MIC50) (MIC50) (MIC50) species C. albicans 05 < 025 05 003 003 C. tropicalis 025 < 025 1 006 006 C. glabrata 05 < 025 2 006 006 C. parapsilosis 025 < 025 2 2 2 C. krusei 025 16 2 025 013 C. lusitaniae >1 < 025 1 1 025 MIC50, median minimum inhibitory concentration (μg/ml). aSusceptibilities were calculated on the basis of NCCLS methodology. bPfaller et al.(5). cOstrosky-Zeichner L et al.(3). Table 7.5 Interpretive breakpoints for Candida species Minimum inhibitory concentration (MIC, μg/ml) Drug S S-DD or I R Fluconazole ≤8 S-DD, 16–32 >32 Itraconazole ≤0.125 S-DD, 0.25–0.5 >0.5 Flucytosine ≤4 I, 8–16 >16 Voriconazole ≤1 S-DD, 2 >4 S, susceptible; R, resistant; S-DD, susceptible-dose dependent; I, intermediate. topical nystatin. The echinocandin class of antifungals has excellent fungicidal activity against Candida species. 7.1. Cutaneous Candidiasis Most localized, cutaneous candidiasis infections can be treated with topical antifungal agents, such as clotrimazole, econazole, ciclopirox, miconazole, ketoconazole, and nystatin. If the infection is a paronychium, the most important aspect of the therapy is drainage of the abscess, followed by oral antifungal therapy with either fluconazole or itraconazole. In cases of extensive cutaneous infections, infections in immunocompromised patients, folliculitis, or onychomycosis, systemic antifungal therapy is recommended. For Candida onychomycosis, oral itraconazole appears to be the most efficacious of azoles. Two treatment regimens are available: a single daily dose of itraconazole taken for 3 to 6 months or a pulsed-dose regimen that requires a slightly higher dose daily for 7 days, followed by 3 weeks off therapy. The cycle is Table 7.6 Oropharyngeal and esophageal candidiasis treatment options Drug/formulation Dose Comments Nystatin Pastilles or lozenge 200,000 U qida Unpleasant taste; may cause nausea and gastrointestinal Suspension 500,000 U by swish and swallow qid disturbances Vaginal tablet 100,000 U dissolve 1 tablet tid Vaginal tablets in combination with unsweetened mints or chewing gum better tolerated; not recommended for esophagitis Clotrimazole Troches Dissolve in mouth 5 times each day More palatable than nystatin but contains dextrose, which may promote dental caries; not recommended for esophagitis Fluconazole 100 mg/day; loading dose of 200 mg for severe Superior to nystatin, clotrimazole, ketoconazole. High doses (up to Oral suspension or disease 800 mg/day) can be used in difficult cases. Success has been Tablet obtained even in cases with in vitro resistance Itraconazole Solution 200 mg (20 ml) by swish and swallow daily Solution has been tested only among HIV patients, but is much better absorbed and has shown efficacy equivalent to that of fluconazole Capsule 200 mg/day (with food) × 14–28 days Limited bioavailability; absorption improved if taken with fatty meal; efficacy of capsules is thought equal to that of ketoconazole Ketoconazole 200–400 mg/day Limited bioavailability; requires acidic environment for best Tablet absorption; liver toxicity; less efficacious than fluconazole and itraconazole and less frequently used Amphotericin B Suspension 1 ml (1 mg/ml) swish and swallow qid Agent considered second-line option; reserved for severe cases and Lozenge 100 mg qid documented failures to azoles; parenteral dosing necessary for Tablet 10 mg qid esophagitis Parenteral 0.4–0.6 mg/kg per day IV U, units; qid, four times daily; tid, three times daily; IV, intravenously. aAll given for 7–14 days for oropharyngeal candidiasis and up to 21 days for esophageal candidiasis orally, unless otherwise stated. 7. Candidiasis 155 repeated every month for 3 to 6 months. Also effective and well-tolerated is terbinafine 250 mg daily for 6 weeks. 7.2. Gastrointestinal Candidiasis Oropharyngeal candidiasis may be treated with topical antifungal agents (nystatin, clotrimazole, amphotericin B oral suspension) or with systemic oral azoles (fluconazole, itraconazole) (Table 7.6). Candida esophagitis requires systemic therapy, usually with fluconazole or itraconazole for at least 14 to 21 days. Parenteral therapy with fluconazole may be required initially if the patient is unable to take oral medications. Daily suppressive antifungal therapy with fluconazole 100 to 200 mg/day is effective in preventing recurrent episodes, but it should be used only if the recurrences become frequent or are associated with malnutrition from poor

oral intake and wasting syndrome. In patients with advanced AIDS and severe immunodeficiency, recurrent candidal esophagitis due to azole-resistant C. albicans or C. glabrata can be treated effectively with voriconazole or caspofungin (27,28). Table 7.7 Azole therapy for vaginal candidiasis Drug Formulation Dosage Butoconazole 2% cream 5 g × 3 d (single dose) 2% vaginal suppository 1 suppository (5g) once daily × 7–14 d Clotrimazole 1% cream 5 g × 7–14 days 10% cream 5 g single application 100-mg vaginal tablet 1 tablet × 7 days 100-mg vaginal tablet 2 tablets × 3 days 500-mg vaginal tablet 1 tablet once Econazole 150-mg vaginal tablet 1 tablet × 3 days Fenticonazole 2% cream 5 g × 7 days Miconazole 2% cream 5 g ×7 days 100-mg vaginal suppository 1 suppository × 7 days 200-mg vaginal suppository 1 suppository × 3 days 1200-mg vaginal suppository 1 suppository once Tioconazole 2% cream 5 g × 3 days 6.5% cream 5 g single dose Terconazole 0.4% cream 5 g × 7 days 0.8% cream 5 g × 3 days 80-mg vaginal suppository 80 mg × 3 days Fluconazole Oral tablet 150 mg single dose Ketoconazole 200-mg tablet 400 mg × 5 days Itraconazole 100-mg tablet 200 mg × 3 days 156 Jack D. Sobel 7.3. Genital Tract Candidiasis Vulvovaginal candidiasis can be managed with either topical antifungal agents or single-dose oral fluconazole in uncomplicated infections (Table 7.7). Single-dose (150 mg) oral fluconazole is the preferred method of treatment and typically preferred by women. This therapy has been shown to have clinical and microbiologic efficacy as good as that of topical antifungal agents. A small percentage of women (<5%) suffer from chronic recurrent VVC infections, which often require chronic or prophylactic oral azole therapy for control. In women who suffer from recurrent attacks, the recommended regimen is fluconazole at a dose of 150 mg every third day for three doses, followed by weekly fluconazole at a dose of 150 mg for 6 months. This regimen prevents recurrent infections in more than 90% of women, although symptomatic recurrence is common after cessation of maintenance suppressive prophylaxis (29). 7.4. Urinary Tract Candidiasis (Candiduria) Asymptomatic candiduria in urinary catheterized patients is extremely common and most commonly reflects yeast colonization of the catheter and lower urinary tract and hence no antifungal therapy is not indicated. Symptomatic candiduria reflects deep tissue or parenchymal invasion and results in organ specific as well as constitutional symptoms (e.g., fever, frequency, dysuria [lower urinary tract] or fever, renal angle pain, nausea, vomiting, and even sepsis [pyelonephritis]). While amphotericin B IV has been the mainstay of indicated therapy, accompanying drug nephrotoxicity limits its use. Fluconazole, 400 mg daily, achieves high urinary concentrations and has emerged as the drug of first choice with small dose adjustments required for coexistent renal insufficiency. None of the other azoles, including voriconazole, are excreted in urine. Similarly, the echinocandins achieve minimal subtherapeutic urine concentrations. A useful agent for eradicating non-albicans candidemia, especially C. glabrata, is oral flucytosine in the absence of renal failure. Deep tissue invasion of kidneys or bladder can be treated by all the systemically active antifungals. 7.5. Candidemia and Acute Disseminated Candidiasis Candidemia requires treatment in all patients (Tables 7.8 and 7.9) and is related to the presence of an intravascular catheter in up to 80% of non-neutropenic patients. Removal of intravascular catheters shortens the duration of candidemia and has been associated with reduced mortality. Although some patients have been cured by catheter removal alone, even transient episodes of candidemia can be associated with hematogenous spread and subsequent diagnosis of endophthalmitis or osteomyelitis. Thus, all episodes of candidemia mandate antifungal therapy. A dilated retinal examination is important in all candidemic patients. Although amphotericin B has been the standard approach, two prospective randomized trials and two retrospective reviews compared amphotericin B with fluconazole (2). The studies demonstrated that amphotericin B at 0.5 to 0.6 mg/kg per day and fluconazole at 400 mg/day are equivalent as effective therapy of candidemia in non-neutropenic patients. In all studies, most isolates were C. albicans. The strength 7. Candidiasis 157 Table 7.8 First-line therapy for candidemia and invasive candidiasis Polyenes Amphotericin B deoxycholate 0.5–0.7 mg/kg IV daily Liposomal amphotericin B 3–5 mg/kg IV daily Lipid complex amphotericin B 3–5 mg/kg IV daily Azoles Fluconazole 400–800 mg IV daily Itraconazole 200 mg IV q12h × 4 doses, followed by 200 mg IV daily Voriconazole 6 mg/kg IV q12h × 2 doses, followed by 3 mg/kg IV q12h Posaconazole PO (not yet approved) Echinocandins Caspofungin 70 mg IV × 1 dose, followed by 50 mg IV daily Micafungin 100 mg IV dailya Anidulafungin 200 mg IV × 1 dose, followed by 100 mg IV daily IV, intravenously; PO, by mouth; q12h, every 12 hours. aSuggested, but not finalized dose. of the study data is equally convincing for non-albicans Candida species. Certain non- albicans Candida, especially C. glabrata, have higher fluconazole minimum inhibitory concentrations, so higher antifungal doses may be required for optimal outcome (3). Caspofungin was also approved for candidemia and invasive candidiasis, based on data from one study that showed caspofungin to be as good as, if not superior to, amphotericin B in patients with candidemia (30). The broad-spectrum anti-Candida activity of echinocandins together with rapid fungicidal action makes the echinocandin class highly suitable for therapy, especially given their safety profile and ease of use in renal failure and liver disease: In a recent study, anidulafungin was found to be non-inferior to fluconazole in candidemic patients (31). Voriconazole has been shown to be equivalent to a strategy of amphotericin B therapy followed by fluconazole (32). Table 7.9 Management of candidemia and disseminated candidiasis For C. albicans, C. parapsilosis, C. tropicalis, C. lusitaniae, C. dubliniensis Fluconazole 800 mg IV × 1 dose, followed by 400 mg Caspofungin 70 mg IV × 1 dose, followed by 50 mg IV daily For C. glabrata (select therapy on the basis of MICs) Caspofungin (as above) Voriconazole 6 mg/kg IV q12h × 2 doses, followed by 3 mg/kg IV q12h Amphotericin B 0.7–1.0 mg/kg IV daily Fluconazole 800 mg IV daily For C. krusei Caspofungin (as above) Voriconazole (as above) IV, intravenously; PO, by mouth; q12h, every 12 hours. 158 Jack D. Sobel Accordingly, a number of potent antifungal agents can be empirically selected in the initial therapy candidemia. Many clinicians treat C. glabrata fungemia with intravenous (IV) fluconazole 800 mg/d (12 mg/kg) in adults with normal renal function (26,33). The results of only one noncomparative study suggest that 800 mg/day may produce a better response rate than 400 mg/day for C. albicans fungemia. Choosing between the initial polyene, triazole or echinocandin, is somewhat arbitrary; however, in unstable, critically ill patients with little margin for error, or in patients previously exposed to fluconazole, initiating treatment with amphotericin B or an echinocandin is recommended (33). Moreover, a study by the Mycoses Study Group suggests a possible advantage in initiating treatment with a combination of fluconazole and amphotericin B. Combinations of either fluconazole or amphotericin B with flucytosine at 100 to 150 mg/kg per day may be useful in some patients, but the precise role of this combination is unclear. The required duration of antifungal therapy is undetermined, but therapy is usually continued for about 2 weeks after the last positive blood culture (26). With this approach, the rate of subsequent recurrent infection at a hematogenously seeded site is about 1%. Although the gut has been implicated as a potential source of candidemia only in non-neutropenic patients, it appears likely that the GI tract is the most common source of candidemia in neutropenic patients. In these patients, removal of intravenous catheters may still be important. One notable exception is C. parapsilosis fungemia, which is highly associated with intravascular catheters in cancer patients. Recovery of marrow function is critical, and no therapeutic approach is consistently successful in the face of persistent leukopenia. In this setting, most available experience is with the use of amphotericin B at 0.6 to 1.0 mg/kg per day, given until recovery of marrow function. The optimal dose of amphotericin B is not certain, but non-albicans Candida require higher doses (0.8 to 1.0 mg/kg per day) of amphotericin B. This appears to be especially true of C. krusei and C. glabrata. Use of flucytosine in neutropenic patients is generally limited because of its potential for marrow suppression and the lack of a readily available intravenous formulation. Patients may develop candidemia while receiving antifungal therapy, including prophylactic antifungals. Such breakthrough candidemia may be the result of an infected unremoved intravascular catheter. In cancer patients, breakthrough candidemia has been associated with a higher mortality and has occurred more often during an ICU stay, during prolonged neutropenia, and with the use of corticosteroids. In this setting, immunosuppression should be reduced and factors that might alter antifungal drug delivery or clearance excluded. Intravenous catheters should be changed and the possibility of drug resistance considered, especially since non-albicans Candida are frequently responsible. Antifungal drug susceptibility tests should be performed and therapy should be changed to an antifungal of a different class. Central tunneled catheters in febrile neutropenic patients do not require mandatory removal because alternate vascular access sites are less available, removal is more difficult, and, most importantly, such catheters are less likely to be the source of candidemia, although they may become infected secondarily to bloodstream infection. 7. Candidiasis 159 Occasionally, these valuable access sites can be salvaged using the controversial antibiotic lock method using amphotericin B, but results are unpredictable. 7.6. Chronic Disseminated Candidiasis Therapy of chronic disseminated candidiasis or HSC traditionally consists of prolonged therapy with amphotericin B alone, but this approach has not been uniformly successful. Amphotericin B 0.5 to 1.0 g, followed by a prolonged course of fluconazole 200 to 400 mg/day for 2 to 14 months, is associated with cure rates of greater than 90%. Use of fluconazole is sometimes successful when therapy with amphotericin B is not. Lipid-based amphotericin B has also been used successfully. If the lesions have stabilized and the patient is clinically improved, antineoplastic therapies (including those that induce neutropenia) may be restarted, while antifungal therapy is continued. The duration of antifungal therapy is determined by imaging studies of the liver and spleen. 8. PREVENTION 8.1. Prophylaxis of Candidiasis in Transplant Patients Invasive candidal infections are a concern in these high-risk groups. Institutions with recipients of solid organ and bone marrow transplants usually consider prophy- laxis with fluconazole for the prevention of candidiasis in selected patients only (34). Fluconazole is generally started 1 day before neutropenia, and although controversial, some investigators support its use for 75 to 100 days after bone marrow transplan- tation. In liver transplants, short-term fluconazole prophylaxis is indicated in selected high-risk patients. 8.2. Prophylaxis of Superficial Candidiasis in HIV-Positive Patients There is little support for primary or secondary prevention of OPC, esophageal candidiasis, or vaginal candidiasis in HIV-positive patients. Concern about potential development of resistance or colonization by resistant species or strains of Candida exists. Prophylaxis may be indicated in a select group of patients with recurrent episodes of symptomatic candidiasis only. 8.3. Empirical Anti-Candida Treatment Empirical use of antifungal agents in febrile patients in ICUs is widely used without data to support its use. Given the existent difficulties in diagnosing invasive candidiasis, it appears reasonable to recommend empirical antifungal therapy in selected febrile, high-risk patients with persistent antibiotic resistant fever. Although caspofungin with its broad spectrum may be preferable, less expensive, empirical fluconazole is recom- mended. The use of empirical antifungals in low-risk patients is not justified (35). REFERENCES 1. Calderone RA. Candida and candidiasis. Washington, DC: ASM Press, 2001. 2. Edwards JE. Candida species. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 6th ed. Philadelphia: Elsevier Churchill Livingstone, 2005;2938–2957. 160 Jack D. Sobel 3. Ostrosky-Zeichner L, Rex JH, Pappas PG, et al. Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States. Antimicrob Agents Chemother 2003;47:3149–3154. 4. Jarvis WR. Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infect Dis 1995;20:1526–1530. 5. Morgan J. Global trends in candidemia: review of reports from 1995–2005. Curr Infect Dis Rep 2005;7:429–439. 6. Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP. National surveillance of nosocomial bloodstream infection due to Candida albicans: frequency of occurrence

and antifungal susceptibility in the SCOPE Program. Diagn Microbiol Infect Dis 1998;31: 327–332. 7. Pappas PG, Rex JH, Lee J, et al. A prospective observational study of candidemia: epidemi- ology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis 2003;37:634–643. 8. Bodey GP, Anaissie EJ, Edwards JE. Definition of Candida infections. In: Bodey GP, ed. Candidiasis: pathogenesis, diagnosis, and treatment. New York: Raven Press Ltd, 1993:407–409. 9. McNeil MM, Nash SL, Hajjeh RA, et al. Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 2001;33:641–647. 10. Gudlaugsson O, Gillespie S, Lee K, et al. Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis 2003;37:1172–1177. 11. Pittet D, Tarara D, Wenzel RP. Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1994;271:1598–1601. 12. Marr KA, Seidel K, White TC, Bowden RA. Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. J Infect Dis 2000;181:309–316. 13. Abi-Said D, Anaissie E, Uzun O, Raad I, Pinzcowski H, Vartivarian S. The epidemi- ology of hematogenous candidiasis caused by different Candida species. Clin Infect Dis 1997;24:1122–1128. 14. Samonis G, Anaissie EJ, Rosenbaum B, Bodey GP. A model of sustained gastrointestinal colonization by Candida albicans in healthy adult mice. Infect Immun 1990;58:1514–1517. 15. Yeo E, Alvarado T, Fainstein V, Bodey GP. Prophylaxis of oropharyngeal candidiasis with clotrimazole. J Clin Oncol 1985;3:1668–1671. 16. Kodsi BE, Wickremesinghe C, Kozinn PJ, Iswara K, Goldberg PK. Candida esophagitis: a prospective study of 27 cases. Gastroenterology 1976;71:715–719. 17. Platt R, Polk BF, Murdock B, Rosner B. Risk factors for nosocomial urinary tract infection. Am J Epidemiol 1986;24:977–985. 18. Kauffman CA, Vazquez JA, Sobel JD, et al. Prospective multicenter surveillance study of funguria in hospitalized patients. The National Institute for Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis 2000;30:14–18. 19. Kozinn PJ, Taschdjian CL, Goldberg PK, Wise GJ, Toni EF, Seelig MS. Advances in the diagnosis of renal candidiasis. J Urol 1978;19:184–187. 20. Calandra T, Bille J, Schneider R, Mosimann F, Francioli P. Clinical significance of Candida isolated from peritoneum in surgical patients. Lancet 1989;2:1437–1440. 21. Eggimann P, Garbino J, Pittet D. Management of Candida species infections in critically ill patients. Lancet Infect Dis 2003;:772–785. 22. Pappas PG, Rex JH, Lee J, et al. A prospective observational study of candidemia: epidemi- ology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis 2003;3:634–643. 7. Candidiasis 161 23. Franklin WG, Simon AB, Sodeman TM. Candida myocarditis without valvulitis. Am J Cardiol 1976;38:924–928. 24. Odabasi Z, Mattiuzzi G, Estey E, et al. Beta-d-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis 2004;39:199–205. 25. Pfaller MA, Diekema DJ, Jones RN, Messer SA, Hollis RJ, SENTRY Participants Group. Trends in antifungal susceptibility of Candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY Antimicrobial Surveillance Program, 1997 to 2000. J Clin Microbiol 2002;40:852–856. 26. Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis 2004;38:161–189. 27. Ally R, Schurmann D, Kreisel W, et al. A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis 2001;33:1447–1454. 28. Villanueva A, Gotuzzo E, Arathoon EG, et al. A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis. Am J Med 2002;113:294–299. 29. Sobel JD, Wiesenfeld HC, Martens M, et al. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med 2004;351:876–883. 30. Mora-Duarte J, Betts R, Rotstein C, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002;347:2020–2029. 31. Reboli A, Robstein C, Pappas P, Schrantz J, Krause D, Walsh T. Anidulafungin versus fluconazole for treatment of candidemia and invasive candidiasis. 45th Interscience Conference of Antimicrobial Agents and Chemotherapy, Washington DC, 2005, Dec 16–19, Abstract M-718, p 418. 32. Kullberg BJ, Sobel JD, Ruhnke M, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidemia in non-neutropenic patients: a randomized non-inferiority trial. Lancet 2005;366:1435–1442. 33. Spellberg BJ, Filler SG, Edwards Jr JE. Current treatment strategies for disseminated candidiasis. Clin Infect Dis 2006;42:244–251. 34. Goodman JL, Winston DJ, Greenfield RA, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 1992;326:845–851. 35. Golan Y, Wolf MP, Pauker SG, Wong JB, Hadley S. Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost-effectiveness analysis. Ann Intern Med 2005;143:857–869. SUGGESTED READINGS Calderone RA. Candida and candidiasis. Washington, DC: ASM Press, 2001. Edwards JE. Candida species. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 6th ed. Philadelphia: Elsevier Churchill Livingstone, 2005:2938–2957. Pappas PG, Rex JH, Lee J, et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis 2003;3:634–643. Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis 2004;38:161–189. Spellberg BJ, Filler SG, Edwards Jr JE. Current treatment strategies for disseminated candidiasis. Clin Infect Dis 2006;42:244–251. 8 Infection Due to Non-Candidal Yeasts Jose A. Vazquez, MD 1. INTRODUCTION Yeasts exist throughout nature in association with soil, plants, mammals, fish, and insects, and as a result, humans are constantly exposed to many yeast genera through varying routes. Depending on the interaction between host defense mechanisms and fungal virulence factors, the association between yeast and humans can be either transient or persistent, and can associated with either local infection or systemic disease. Most yeast organisms are of low virulence and generally require significant alterations or reductions in host defenses before tissue invasion. Recently, however, because of the increased population of immunocompromised patients, the frequency of invasive infections due to yeast as well as the number of organisms causing disease continue to grow (1,2) (Table 8.1). 2. TRICHOSPORON Trichosporon asahii was first described in 1865 by Beigel, who identified it as the causative agent of hair infections (3). Infections due to Trichosporon may be classified as superficial or deep. Disseminated infections are increasingly recognized in the compromised host over the past decade and are frequently fatal (1,2). One of the first reported cases of disseminated disease was described in a 39-year-old woman with lung cancer who subsequently developed a brain abscess (4). 2.1. Etiologic Agents The genus Trichosporon was first reported by Behrend (5). Gueho and colleagues have suggested that the species known as T. asahii may include several different Trichosporon species with epidemiological and pathogenic differences (6). Kemker et al., using isoenzyme delineation and polymerase chain reaction (PCR) DNA finger- printing suspect that strains that produce superficial infections are distinctly different from those strains that produce invasive infection (7). There are currently seven species of Trichosporon. These include T. asahii (formerly, T. beigelii), the most frequently recovered species from invasive infections, and T. mucoides and T. inkin, also known From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 163 164 Jose A. Vazquez Table 8.1 Yeasts other than Candida and Cryptococcus that occasionally cause human infection Trichosporon T. asahii (T. beigelii) T. inkin T. Mucoides Saccharomyces S. cerevisiae S. boulardii Rhodotorula R. mucilaginosa (rubra) R. glutinis Malassezia M. furfur M. pachydermatis Blastoschizomyces capitatus (Geotrichum capitatum, Trichosporon capitatum) Sporobolomyces S. Salmonicolor S. holsaticus to cause systemic infections (1,2,8). T. asteroides and T. cutaneum generally produce superficial skin infections, while T. ovoides generally causes white piedra of the scalp and T. inkin, white piedra of the pubic hair. Trichosporon capitatum is now known as Blastoschizomyces capitatus (5,6). Trichosporon species are characterized by true hyphae, pseudohyphae, arthroconidia, and blastoconidia (5) (Fig. 8.1). T. asahii grows readily on Sabouraud dextrose agar, producing smooth, shiny gray to cream colored yeast-like colonies with cerebriform radiating furrows that become dry and membranous with age. All Trichosporon species are easily identified via commercially available carbohydrate assimilation assays. 2.2. Epidemiology T. asahii is generally found in the soil, but may also be recovered from air, rivers and lakes, sewage, and bird droppings (1,2). It rarely colonizes the inanimate environment, but can colonize the mucosal surfaces of the oropharynx, the lower gastrointestinal tract, and the skin of humans (9). More than 100 documented cases of disseminated infection due to Trichosporon species have been reported, most due to T. asahii (1,2,5). The major risk factors associated with infection include hematologic malignancies (acute leukemia, chronic leukemia, multiple myeloma), solid tumors, and neutropenia (1,2). In non-neoplastic, non-neutropenic cases, the major risk factors include corticosteroids, prosthetic valve replacement, solid organ transplantation, chronic active hepatitis, and occasionally intravenous drug use (Table 8.2). The most common portal of entry appears to be the 8. Infection Due to Non-Candidal Yeasts 165 Fig. 8.1. Trichosporon species produce yeast-like colonies in culture and are unique in their production of hyphae, pseudohyphae, arthroconidia, and blastoconidia (budding) both in culture and in disease. (Courtesy of D. R. Hospenthal.) [Figure in color on CD-ROM]. either the respiratory or gastrointestinal tracts. Infrequently, central venous catheters and other vascular devices have also been implicated (10,11). 2.3. Clinical Manifestations Trichosporonosis is classified into superficial infections (white piedra [hair shaft infection], onychomycosis, and otomycosis) and invasive infections. Table 8.2 Risk factors associated with Trichosporon infection Hematologic malignancy Solid organ transplantation (kidney, heart, liver) Neutropenia Broad-spectrum antibiotics Corticosteroids Use of intravenous lipids Bone marrow transplant Chronic active hepatitis IVDU Central venous catheters CAPD Burns 166 Jose A. Vazquez Deep tissue infections may involve either a single organ or multiple organs. The most commonly infected tissue is the lungs, accounting for approximately 33% of all localized deep tissue infections (1,2,10,12,13). Other sites of infection may include the peritoneum, heart valves (natural and prosthetic), retina, liver, spleen, kidneys, gallbladder, and central nervous system (brain abscess and chronic fungal meningitis) (1,2,10,12,13). The signs and symptoms of disseminated infection resemble those of systemic candidiasis and include fungemia with associated organ infection. Moreover, dissem- inated infections may present as either acute or chronic disease. Acute dissemi- nated trichosporonosis often has a sudden onset and progresses rapidly, especially in neutropenic patients. Patients may develop skin lesions (∼33%), pulmonary infiltrates (∼30% to 60%), or renal and ocular involvement. The metastatic cutaneous lesions generally begin as an erythematous rash with raised papules on the trunk and the extremities. The rash eventually evolves into macronodular lesion, followed by central necrosis of the nodules and occasionally formation of hemorrhagic bullae. The pulmonary infiltrates may present as lobar consolidations, bronchopneumonia, or reticulonodular patterns. Renal involvement occurs in more than 75% of the disseminated infection cases. Renal disease may manifest as proteinuria, hematuria, red blood cell casts, with either acute renal failure or acute glomerulonephritis (10). Urine cultures are frequently positive for Trichosporon and suggest disseminated disease, especially in immuno- compromised patients. Chorioretinitis is not uncommon in disseminated infection and may be a cause of visual alterations due to retinal vein occlusion or retinal detachment (10). For unexplained reasons, Trichosporon has been found to have tropism for the choroid and retina. However, unlike candidal endophthalmitis, Trichosporon infects uveal tissues including the iris, but spares the vitreous (14). During disseminated infection, any tissue in the body may become infected. The organs most frequently include the liver, spleen, gastrointestinal tract, lymph nodes, myocardium, bone marrow, pleura, brain, adrenal gland, and thyroid gland (1,2,10,11). In chronic disseminated infection subtle manifestations may be present for several weeks and frequently include persistent fever of unknown etiology (1,2,10). The infection is similar to the entity known as chronic disseminated (hepatosplenic) candidiasis. It is generally a chronic infection of the liver, spleen, and other tissues after recovery from neutropenia. Laboratory studies frequently reveal an elevated alkaline phosphatase. Computed tomography (CT) scan or magnetic resonance imaging (MRI) frequently reveals hepatic or splenic lesions compatible with abscesses. A tissue biopsy is needed to confirm the diagnosis. 2.4. Diagnosis The diagnosis is made with a biopsy of the skin or involved organs. Blood cultures may occasionally be useful in deep tissue infection, but are positive only late in the course of infection. Trichosporon grows readily in

conventional blood culture and on standard fungal media including Sabouraud dextrose agar (5). The presence 8. Infection Due to Non-Candidal Yeasts 167 of Trichosporon in the urine of a high-risk patient should increase the suspicion of disseminated infection. Although there are no standardized serologic assays, the serum latex agglutination test for C. neoformans may be positive. A potential usefulness of this assay has been postulated based on the report of positive serum latex agglutination test for C. neoformans in several patients with disseminated Trichosporon infection (15,16). 2.5. Treatment Disseminated trichosporonosis has a mortality rate of approximately 60% to 70% (1,2). In most cases, however, the underlying disease contributes greatly to the overall mortality. First-line, optimal antifungal therapy has not been established. The initial step in the management of disseminated Trichosporon infection should be to decrease or reverse immunosuppression. In vitro susceptibility studies of Trichosporon species are limited (Table 8.3). In vitro susceptibility assays of T. asahii, reveal fluconazole MIC90 (minimal inhibitory concentration for 90% of isolates) of 4.0 μg/ml, itraconazole MIC90 of 0.25 μg/ml, and an amphotericin B MIC90 of 4.0 μg/ml. In general, most strains have relatively high MICs for polyenes, flucytosine, and echinocandins, with relatively low MICs for the azoles. Among the newer triazoles, voriconazole and posaconazole have demonstrated excellent in vitro activity (17). In vitro and animal models suggest that azoles and not polyenes are more effective in the eradication of Trichosporon species (1,2,13,14). Suggested therapy for the treatment of disseminated disease includes the use of either voriconazole 3 mg/kg IV or 200 mg orally twice daily, fluconazole 400 to 800 mg/day, or itraconazole 400 to 600 mg/day (Table 8.4). A potential option in patients failing azole therapy may also include a combination of an azole with an echinocandin. Serena et al. demonstrated in vitro synergy and improved outcomes in an animal model of trichosporonosis with either the combination of amphotericin B–micafungin or fluconazole–micafungin (18). However, because of the high MICs to polyenes and echinocandins, these antifungals should not be used alone or as first-line therapy. In a patient with disseminated infection and poor response to therapy, in vitro susceptibility testing of recovered isolates may be a helpful adjunct. 3. SACCHAROMYCES Saccharomyces is an ascomycetous yeast found throughout nature. Saccharomyces is commonly known as “brewer’s yeast” or “baker’s yeast.” It is best known for its commercial use in beer and wine production, in health food supplements, and more recently, its use in DNA recombinant technology. Occasionally, these yeasts have been reported to cause severe infection in immunocompromised hosts (5). Species include S. cerevisiae, S. boulardii (a subtype of S. cerevisiae), S. fragilis, and S. carlsbergensis. Saccharomyces may occasionally be part of the normal flora of the gastrointestinal and genitourinary tracts (1,2,19). Recently, S. cerevisiae has been found to cause mucosal and disseminated infection in humans, primarily in immunocompromised hosts (19–22). Table 8.3 In vitro antifungal activity against emerging yeast infections Minimum inhibitory concentration (MIC; μg/ml) rangea Organism Flu Itra Vori Posa Mica Cas Anid AMB 5FC Trichosporon 1–16 0.06– 0.25 0.03–>16 0.06–>16 16–654 4–>16 16–>16 1–8 16–>512 Saccharomyces 0.5–64 0.03–4 0.016–2 0.12–1.0 NA 0.25–1 0.25–1 0.032–4 < 0.125–1 Rhodotorula 0.5–>64 0.25–>16 0.25–>8 0.25–>8.0 >64 8–>64 >64 0.12–1.0 0.6–0.25 Malassezia 1.0–16 0.03–0.25 0.03–0.125 0.03–32 NA NA NA 0.3–2.5 >100 Blastoschizomyces 1–32 0.03–0.50 0.03–0.50 0.12–0.25 NA NA 1–4 0.6–0.25 0.12–16 Sporobolomyces 1.25–>64 1.0–2.0 0.25–4.0 NA >64 NA NA 0.14–1.0 NA Flu, fluconazole; Itra, itraconazole; Vori, voriconazole; Posa, posaconazole; Mica, micafungin; Cas, caspofungin; Anid, anidulafungin; AMB, amphotericin B; 5FC, flucytosine; NA, data not available. aClinical Laboratory Standards Institute (CLSI) testing criteria and breakpoints have not been established for any of these fungi. 8. Infection Due to Non-Candidal Yeasts 169 Table 8.4 Suggested antifungal agents for use in treatment of emerging yeast infections Yeast Antifungal therapya Trichosporon Fluconazole 400 mg/day Voriconazole 200 mg bid Itraconazole 400–600 mg /day Saccharomyces Amphotericin B 5-Flucytosine Azoles (ketoconazole, clotrimazole, miconazole) Rhodotorula Amphotericin B + 5-flucytosine Malassezia Fluconazole 400 mg/day Voriconazole 200 mg bid Amphotericin B 0.7 mg/kg/day Blastoschizomyces Amphotericin B 1–1.5 mg/kg/day Sporobolomyces Amphotericin B Azoles (ketoconazole, itraconazole, fluconazole) aNo antifungal agents have specific FDA approval for therapy of any of these infections. No randomized clinical trials have been performed. Selections are based on in vitro data, limited animal studies, and/or individual case reports. 3.1. Etiologic Agents Cells are oval to spherical and exist as either haploids or diploids. When present, ascospores, one to four in number, are in either tetrahedral or linear arrangement and stain gram negative; vegetative cells stain gram positive. Colonies are smooth, moist, and either white or cream-colored. Saccharomyces are generally nonpathogenic because of innate low virulence (23–25). Investigators evaluating more than 3300 yeast cultures obtained from cancer patients found only 19 isolates of S. cerevisiae. Recent studies by Clemons et al. using an animal model have been able to show that some strains of S. cerevisiae, when introduced into CD-1 mice, can proliferate and resist clearance in vivo, supporting the role of S. cerevisiae as a cause of clinical infection in humans (25). 3.2. Epidemiology Isolation of Saccharomyces species from human surfaces is rarely of any clinical significance. It has been recovered from the bloodstream, lungs, peritoneal cavity, esophagus, urinary tract and vagina (19,23,26). Genotyping studies evaluating the relat- edness between clinical strains and commercial strains of S. cerevisiae have demon- strated that commercial products may occasionally be a contributing factor in human colonization and infection (27). Nyirjesy et al. reported that four women suffering from recurrent S. cerevisiae vaginitis had also experienced exposure to bread dough that contained identical strains S. cerevisiae (22). The risk factors associated with Saccharomyces infections are similar to the risk factors associated with candidemia and systemic candidiasis, including central 170 Jose A. Vazquez venous catheters, neutropenia, use of antimicrobials, gastrointestinal tract surgery, and occasionally HIV (21,28–30). The portal of entry for invasive disease is most likely the oropharynx or gastrointestinal tract (29). 3.3. Clinical Manifestations Manifestations are generally nonspecific and indistinguishable from those associated with candidemia and invasive candidiasis. In addition, Saccharomyces has been associated with bloodstream infections, endocarditis, peritonitis, disseminated disease and vaginitis (1,2,19,22,26,28–32) Fungemia is the most common form of infection, occurring in approximately 70% of reported cases. As in invasive candidiasis, it is seen primarily in the immuno- compromised host and tends to be associated with use of intravascular catheters, chemotherapy, and/or antimicrobials (20,21,29). Manifestations are similar to those of systemic candidiasis and candidemia. Overall, fever unresponsive to broad spectrum antimicrobials is the most frequent manifestation. Unlike patients with infections due to Candida species, most patients with Saccharomyces infections survive. In addition, it is not uncommon for other organ systems to become infected, including the respiratory tract, with several documented episodes of pneumonia and empyema. Diagnosis is generally established by histopathology, because Saccharomyces can colonize the respiratory tract without producing invasive disease (20,29,33). Saccha- romyces has also been reported to produce peritonitis, cholecystitis, and endocarditis (20,29). All cases of endocarditis were associated with prosthetic valves and intra- venous heroin use. Further, two out of the three patients were cured with antifungal therapy, while only one patient had their valve replaced. There have also been several documented cases of urinary tract infections due to S. cerevisiae (26,29). All patients had urologic abnormalities that were underlying or associated with fungemia (29). Mucosal infections due to S. cerevisiae have also been reported. Sobel et al. reported on 17 women with difficult to manage vaginitis due to S. cerevisiae (19,22). In fact, the women with symptomatic vaginitis had manifestations indistinguishable from those caused by C. albicans. All patients had a history of chronic vaginitis unresponsive to conventional antifungals and all but two had systemic or local predisposing factors. 3.4. Diagnosis Because of the fact that Saccharomyces species have a tendency to be nonpathogenic, the decision to attribute a causal role to S. cerevisiae is difficult. Diagnostic diffi- culty occurs when the organism is recovered from body sites that may be colonized by Saccharomyces, especially in the absence of symptoms of infection. Unless the organism is found in the bloodstream, it is frequently necessary to determine whether these yeasts are causing true infection versus colonization. This is generally done via a histopathologic examination. S. cerevisiae readily grows from blood culture bottles and on Sabouraud dextrose media. 3.5. Treatment It is often difficult to assess the role of antifungal therapy in patients with infection due to Saccharomyces. There are several reports that document resolution of fungemia 8. Infection Due to Non-Candidal Yeasts 171 and infection just by removing the intravascular catheter without providing antifungal therapy (28,29). Most experts advocate removing the focus of infection, whether it is an indwelling or tunneled intravenous catheter and the concurrent use of antifungal agents (29). In vitro susceptibility studies reveal that S. cerevisiae, when compared to C. albicans isolates, are less susceptible to most antifungals, including azoles (2,20) (Table 8.3). Although clinical trials have not be conducted and in vitro suscepti- bility assays are not standardized, Saccharomyces species appear to be susceptible to most antifungals including amphotericin B, 5-flucytosine, ketoconazole, clotrimazole, miconazole, and terconazole (1,2,20,34) (Table 8.4). 4. RHODOTORULA Yeasts of the genus Rhodotorula are found worldwide from a variety of sources and is generally considered a contaminant when identified. Infections are occasionally seen primarily in immunocompromised hosts. 4.1. Etiologic Agents Yeasts of the genus Rhodotorula are imperfect basidiomycetous yeasts belonging to the family Cryptococcaceae. Currently, eight species in the genus Rhodotorula are recognized (2,34,35). Rhodotorula mucilaginosa (formerly R. rubra) is the species most frequently associated with human infections. The other species include R. glutinis, R. pilimanae, R. pallida, R. aurantiaca, and R. minuta. Most Rhodotorula species produce red-to-orange colonies due to the presence of carotenoid pigments (5,36). The yeast is mucoid, encapsulated, and readily grows on many types of culture media. 4.2. Epidemiology Rhodotorula can be isolated from a variety of sources including seawater, plants, air, food, fruit juices, and occasionally from humans (1,2,5,36). It is not unusual to recover it as an airborne laboratory contaminant. Rhodotorula can also be recovered from shower curtains, bathtub-wall junctions, and toothbrushes. In humans, Rhodotorula can be been recovered from skin, nails, respiratory tract, urinary tract, gastrointestinal tract, and bloodstream (1,2,37–41). R. mucilaginosa and R. glutinis account for approximately 0.5% of yeast isolated from the oral cavity and more than 12% of yeast isolates recovered from stool and rectal swabs (42). The recovery of Rhodotorula from nonsterile human sources such as mucosal sites has been of questionable clinical significance. Although a number of invasive infections have been documented, risk factors include underlying immuno- suppression (malignancy, neutropenia, corticosteroids, collagen vascular disease, and uncontrolled diabetes mellitus), use of broad-spectrum antimicrobials, and central venous catheters. 4.3. Clinical Manifestations Manifestations are generally nonspecific, and may vary from subtle and mild, to severe, including septic shock. Rhodotorula have been incriminated in a wide spectrum of infections including bloodstream infections, endocarditis, peritonitis, meningitis, and disseminated disease (34,38,41,43–46) (Table 8.5) 172 Jose A. Vazquez Table 8.5 Clinical manifestations of Rhodotorula infections Fungemia Endocarditis Meningitis Peritonitis Disseminated disease Fungemia is the most common form of infection and is generally due to intravascular catheter infection (1,2,34,38,41,45). Fever of unknown etiology that is unresponsive to broad spectrum antimicrobials is the most frequent manifestation associated with fungemia. Meningitis has also been described in patients with acute leukemia, HIV infection, and postoperatively (47,48). The organisms are generally recovered from the cerebrospinal fluid on culture, and frequently seen on an India ink stain. In addition, several case of R. rubra peritonitis have been described in patients undergoing continuous ambulatory peritoneal dialysis. In these patients, environmental cultures revealed a possible common source outbreak. In all patients, the symptoms were subtle and intermittent at first, consisting of abdominal pain, anorexia, nausea, and occasional diarrhea (2,34). 4.4. Diagnosis In the most proven infections, Rhodotorula is recovered from a sterile site of infection. In these cases, the decision to attribute a causal role to Rhodotorula is relatively simple, and the patient should be treated appropriately for an invasive fungal infection. The more difficult decision is when the organism is recovered from nonsterile body sites that may normally harbor Rhodotorula species, especially in the absence of signs or symptoms of infection. In this setting, it is essential to establish the presence of infection and not just colonization. 4.5. Treatment As with many of the uncommon yeast isolates, it is difficult

to assess the role of antifungal therapy in patients infected with Rhodotorula. Optimal management of patients with indwelling catheters and infection due to Rhodotorula has not been well defined. Several case reports document the clearance of fungemia and the resolution of infection by removing the intravascular catheter without providing antifungal therapy (38,45). Several other documented case reports, however, have suggested that antifungal treatment alone may suffice without having to remove the central venous catheter. Because infections due to Rhodotorula have been severe and life threatening, it is probably best to manage these infections aggressively with catheter removal and antifungal therapy. In vitro susceptibility studies reveal that Rhodotorula are susceptible to amphotericin B and flucytosine, but less susceptible to azoles and resistant to echinocandins (34, 49) (Table 8.3). Although clinical trials have not been conducted, it appears that 8. Infection Due to Non-Candidal Yeasts 173 amphotericin B with or without flucytosine is the best recommendation for antifungal therapy at this time (1,2). In view of the intrinsic resistance of Rhodotorula to the azoles and echinocandins, these agents should not be used as monotherapy unless in vitro susceptibility activity has been assessed. 5. MALASSEZIA Malassezia furfur is a yeast commonly found on human skin. It has been well documented to cause superficial skin infections such as pityriasis (tinea) versicolor and folliculitis. In addition, in immunocompromised host it may occasionally cause invasive infection. 5.1. Etiologic Agents The genus Malassezia consists of several species; the two most frequently isolated species include M. furfur and M. pachydermatis (1,2,5). The other less commonly isolated species include M. sympodialis, M. slooffiae, M. globosa, M. obtuse, and M. restricta. M. furfur is the dominant species recovered in humans as a fungal pathogen. M. furfur is a dimorphic, lipophilic yeast that is unable to synthesize medium or long-chain fatty acids and thus has a strict in vitro requirement for exogenous fatty acids of the C12 and C14 series (50). Although it exists primarily in the yeast form, it may also form filamentous structures on the skin when the organism is associated with superficial infections (51). Because of its nutritional requirements, M. furfur is difficult to recover from clinical specimens unless its presence is suspected and special preparations are made by the microbiology laboratory. The second most common species is M. pachydermatis, which is generally associated with infections in dogs producing otitis externa (50). Occasionally, however, it has been implicated in human infections (51,52). Both Malassezia species, when grown under favorable conditions produce clusters of oval to round, thick-walled yeast cells, with unipolar buds that form repeatedly from the same pole of the parent cell. This gives rise to the characteristic “collarette” at the bud site. Media such as Sabouraud dextrose agar, chocolate agar, and trypticase soy agar with 5% sheep blood all require the addition of supplements such as olive oil to permit the growth of this organism (53). M. pachydermatis, however, does not require exogenous lipids for growth, can be recovered on conventional fungal media, and its colonies tend to be dry and white to creamy in color. 5.2. Epidemiology Malassezia is frequently found on normal individuals colonizing the skin. Distri- bution of this colonization tends to correlate with the more oily areas, most likely because of the organisms’ requirement of exogenous fatty acids found in those areas. Thus, it is found primarily on the scalp, shoulders, chest, and back (53). The highest colonization rates are found in teenagers (>90%). The isolation of M. furfur from newborns is reported to be less than 10% in non- intensive care settings. However, it has been reported to be greater than 80% in neonatal intensive care units (ICUs) (51,53). Risk factors associated with increased colonization rates in neonates include prematurity, duration of hospitalization in the ICU, use of occlusive dressings, and prolonged antimicrobial use (51). Although the epidemiology 174 Jose A. Vazquez Table 8.6 Risk factors associated with Malassezia infections Prematurity Longer duration of hospitalization Use of occlusive dressings Administration of antibiotics Use of central venous catheters Use of intravenous lipids of disseminated infection in adults has not been well studied, there appear to be several risk factors that are frequently associated with deep-seated infections (Table 8.6). These include prematurity, central venous catheters, total parenteral nutrition, parenteral lipid preparations, and immunocompromised state (54–57). Molecular epidemiologic studies using DNA fingerprinting have concluded that within the neonatal ICUs there is longitudinal persistence of both M. furfur and M. pachydermatis strains (58). 5.3. Clinical Manifestations Malassezia generally produces superficial skin infections, such as pityriasis (tinea) versicolor or folliculitis. From time to time, Malassezia may produce a deep-seated or hematogenous infections (54–57). The first reported case of systemic infection was described in 1981 in a premature neonate who developed fungemia and vasculitis while on lipid therapy (57). Since then, numerous reports describing disseminated infection have been published (51,55). The manifestations of disseminated infection vary from subclinical and mild symptomatology, such as fever, to sepsis with associated multi- organ dysfunction (51,55). The majority of the Malassezia infections are diagnosed in premature infants. Occasionally, they may be seen in adults. The most commonly reported manifestations of systemic infection include fever unresponsive to broad- spectrum antimicrobials, bradycardia, respiratory distress, hepatosplenomegaly, and lethargy. 5.4. Diagnosis Laboratory findings include leukocytosis and thrombocytopenia. Chest x-ray exami- nation frequently reveals bilateral pulmonary infiltrates (>50%) (1,2,54). Occasionally, the diagnosis of disseminated infection can be made by a Gram stain of the buffy coat of blood. The budding yeast cells may be observed using different stains such as Giemsa, periodic acid Schiff (PAS), Gomori’s methenamine silver (GMS), or Calcofluor white. Blood cultures are usually negative unless the infection is initially suspected and the laboratory uses a lipid-enriched media. The recovery of the organisms is enhanced by using the lysis centrifugation blood culture technique (59). Palmitic acid (3%) supplementation may also improve the recovery of Malassezia (59). 5.5. Treatment Management of M. furfur fungemia and disseminated infection are controversial. Most authorities recommend prompt removal of the central venous catheter and discon- tinuation of intravenous lipids (54,55). In most cases without a deep-seated infection, 8. Infection Due to Non-Candidal Yeasts 175 removal of the central venous catheter and discontinuation of lipids is all that is needed to clear the infection. This treatment modality accomplishes two objectives: it eradicates the nidus of infection, and removes the nutritional requirements of the organism. If fungemia persists or there is evidence of deep-seated infection, it is prudent to initiate antifungal therapy. Fortunately, Malassezia species are suscep- tible to azoles and polyenes (1,2,34) (Table 8.3). In vitro susceptibility assays of M. furfur strains demonstrate that most of the isolates are susceptible to ampho- tericin B, ketoconazole (MIC range ≤0.05 to 0.4 μg/ml), miconazole (MIC range 0.4≥50 μg/ml), and fluconazole. Most of the isolates are intrinsically resistant to flucy- tosine (MIC90>100 μg/ml) (1,2,34). Although randomized clinical trials have not been conducted, in most situations, either fluconazole 400 mg/day or amphotericin B 0.7 mg/kg per day is sufficient to eradicate the infection (Table 8.4). Based on excellent in vitro activity, itraconazole and voriconazole are also alternate choices. 6. OTHER YEASTS In addition to the yeasts discussed thus far, fewer reports have been published of infection due to other yeasts. These include Blastoschizomyces, Sporobolomyces, Pichia (formerly Hansenula), and Exophiala. 6.1. Blastoschizomyces Blastoschizomyces capitatus (formerly Geotrichum capitatum or Trichosporon capitatum) infections, although less common than those due to T. asahii, have been well described in the literature (60). B. capitatus is found in wood and poultry, but has also been recovered from sputum and normal intact skin (5). Geographically, it appears to be the opposite of T. asahii, with B. capitatus infections found primarily in Europe and T. asahii found in North America (61). In most cases, the major risk factors include neutropenia and underlying hematologic malignancies. Although the portal of entry is unknown, it is suspected to be the either the respiratory tract, gastrointestinal tract, or central venous catheters (35,61). Infection may involve a single organ or multiple organs and may be associated with fungemia. The clinical spectrum of disseminated infection is similar to that of systemic candidiasis and includes fungemia with or without organ infection (1,2,61). By and large, the manifestations begin with fever of unknown etiology and unresponsive to antimicrobials. Diagnosis can be made with blood cultures or on biopsy of the skin or affected organs. Blood cultures have been reported to be positive in more than 80% of cases (61). B. capitatus easily grows in blood culture bottles and on fungal specific media (5). Although skin lesions are commonly seen, fungal stains and cultures from biopsied skin lesions are frequently negative (5,61). Mortality rates between 60% and 80% are generally described (61). However, underlying disease, persistent neutropenia and concurrent infections are significant contributing factors to this overall mortality rate. Optimal therapy has not yet been established. Until recently, however, most patients have received amphotericin B (2). As with all fungal infections, the initial step is to decrease or reverse the immuno- compromised state. In vitro susceptibility studies demonstrate that the organism is susceptible to amphotericin B (MIC90 0.12 g/ml), and less susceptible to azoles such 176 Jose A. Vazquez as fluconazole and ketoconazole (0.04 to 32g/ml), but appears to be susceptible to itraconazole and voriconazole. Most isolates are resistant to flucytosine (5) (Table 8.3). The current recommendation is to use amphotericin B at a dose of 1 to 1.5 mg/kg per day (1,2). However, since the newer azoles, voriconazole and posaconazole, have demonstrated good in vitro activity they may also be suitable alternatives (62). 6.2. Sporobolomyces Sporobolomyces are yeast-like organisms that belong to the family Sporobolomyc- etaceae. These yeast are found throughout the world in soil, bark, and decaying organic material. They have occasionally been associated with infections in humans. There are seven known species of Sporobolomyces, but only three have been documented to cause disease—S. salmonicolor, S. holsaticus, and S. roseus. To date, there have been only six documented cases of Sporobolomyces infections: a nasal polyp, one case of dermatitis, one case of infected skin blisters, one case of mycetoma, and two cases of disseminated infection in patients with acquired immunodeficiency syndrome (AIDS; lymph node and bone marrow) (2,63). In vitro susceptibility studies show that S. salmonicolor is susceptible to amphotericin B and the imidazoles (1,2,5) (Table 8.3). Despite the fact that these organisms are saprophytic, the case reports indicate their potential ability to produce invasive infection in humans, especially in a compromised host. REFERENCES 1. Hospenthal DR. Uncommon fungi. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 6th ed. 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J Clin Microbiol 1995;33:1005–1007. 8. Infection Due to Non-Candidal Yeasts 179 60. Gemeinhardt H. Lungenpathogenitat von Trichosporon capitatum beim menschen. Zentra- blatt fur Bakteriolgie (Series A) 1965;196:121–133. 61. Martino P, Venditti M, Micozzi A, et al. Blastoschizomyces capitatus: an emerging cause of invasive fungal disease in leukemia patients. Rev Infect Dis 1990;12:570–582. 62. Espinel-Ingroff A. Comparison of in vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeast. J Clin Microbiol 1998;36:2950–2956. 63. Morris JT, Beckius M, McAllister CK. Sporobolomyces infection in an AIDS patient. J Infect Dis 1991;164:623–624. SUGGESTED READINGS Diekema DJ, Petroelje B, Messer SA, Hollis RJ, Pfaller MA. Activities of available and investigational agents against Rhodotorula species. J Clin Microbiol 2005;43:476–478. Enache-Angoulvant A, Hennequin C. Invasive Saccharomyces infection: a comprehensive review. Clin Infect Dis 2005;41:1559–1568. Espinel-Ingroff A. Comparison of in vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeast. J Clin Microbiol 1998;36:2950–2956. Hospenthal DR. Uncommon fungi. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 6th ed. Philadelphia: Elsevier Churchill Livingstone, 2005:3068–3079. Marcon MJ, Powell DA. Human infections due to Malassezia spp. Clin Microbiol Rev 1992;5:101–119. Martino P, Venditti M, Micozzi A, et al. Blastoschizomyces capitatus: an emerging cause of invasive fungal disease in leukemia patients. Rev Infect Dis 1990;12:570–582. Vazquez JA. Rhodotorula, Malassezia, Trichosporon, and other yeast-like fungi. In: Dismukes WE, Pappas PG, Sobel JD, eds. Clinical mycology. New York: Oxford University Press, 2003:206–217. 9 Aspergillosis Helen W. Boucher, MD and Thomas F. Patterson, MD 1. INTRODUCTION Aspergillosis is caused by Aspergillus, a hyaline responsible not only for invasive aspergillosis, but also for a variety of noninvasive or semi-invasive conditions. These syndromes range from colonization to allergic responses to Aspergillus including allergic bronchopulmonary aspergillosis (ABPA) to semi-invasive or invasive infec- tions, spanning a spectrum from chronic necrotizing pneumonia to invasive pulmonary aspergillosis. The genus Aspergillus was first recognized in 1729 by Micheli, in Florence, who noted the resemblance between the sporulating head of an Aspergillus species and an aspergillum used to sprinkle holy water (Fig. 9.1). In 1856, Virchow published the first complete microscopic descriptions of the organism (1). The frequency and severity of invasive fungal infections in immunocompromised patients have increased steadily over the past 2 decades with the growing population of patients undergoing transplantation and the persistent challenges in preventing, diagnosing and treating these infections (2). Mortality due to documented invasive aspergillosis approaches 80% to 100% in high-risk patients, including those with under- lying hematologic malignancy or bone marrow or solid organ transplantation, and may be related to several factors, including diagnostic and therapeutic inadequacies (3–5). Apart from organ transplant recipients, individuals with acquired immunodeficiency syndrome (AIDS), and patients hospitalized with severe illnesses, major increases in invasive fungal infections have been observed in patients with hematologic malig- nancies who receive induction or consolidation chemotherapy and those who undergo hematopoietic stem cell transplantation (HSCT) (5). Successful therapy depends not only an early diagnosis—which is often difficult to establish—but even more importantly, on reversal of underlying host immune defects, such as neutropenia or high-dose immunosuppressive therapy (2). Non-culture-based tests and radiological approaches can be used to establish an early diagnosis of infection and may result in improved outcomes of infection (2,6,7). Even when therapy is begun From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 181 182 Helen W. Boucher and Thomas F. Patterson Fig. 9.1. Microscopic morphology of Aspergillus fumigatus showing a single role of phialides (uniseriate) bearing smooth conidia in a columnar fashion. (Courtesy of www.doctorfungus.org). [Figure in color on CD-ROM]. promptly, efficacy of many treatment regimens, including amphotericin B deoxy- cholate, is poor, particularly in patients with disseminated or central nervous system disease (2,3,5). New diagnostic approaches have been introduced and new antifungal agents have been developed for this disease including the newer azoles, lipid formula- tions of amphotericin B, and a new drug class—the echinocandins (8). 2. ETIOLOGIC AGENTS Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi (9). A. fumigatus has emerged worldwide as a frequent cause of nosocomial infection and may be regarded as the most important airborne pathogenic fungus (10). As Aspergillus species can be readily found in the environment, invasive aspergillosis is widely believed to occur as a consequence of exogenous acquisition of the conidia (spores) of the species (10). The most common route of transmission of Aspergillus infection is the airborne route. Aspergillus conidia are resilient and may survive for long periods in fomites (any substance that can absorb, retain, and transport infec- tious species, e.g., woolen clothes or bedding) (11). Aspergillus infection occurs less frequently through damaged mucocutaneous surfaces (e.g., following surgery or through contaminated dressings). However, the sources of Aspergillus may be broader than have traditionally been thought, as waterborne transmission of Aspergillus conidia through contaminated aerosols has been suggested (12). 9. Aspergillosis 183 Table 9.1 Characteristics of common Aspergillus species Aspergillus Mycological Clinical Mycoses species characteristics significance A. flavus Olive to lime Second most common Sinusitis, cutaneous green colonies species, produces infection, pulmonary and aflatoxin, may be disseminated disease less susceptible to polyenes A. fumigatus Smoky, blue- or Most common species Invasive pulmonary gray green, causing invasive aspergillosis, disseminated small, smooth infection infection, CNS, others conidia (2–2.5 μm) A. niger Typically black Common cause of Otomycosis, cutaneous, colonies, radiate otomycosis, endophthalmitis, conidial head, produces oxalate aspergilloma, invasive large rough crystals which may pulmonary or disseminated conidia be seen in host disease less common A. terreus Beige to buff Increasing frequency, Pulmonary, disseminated, colonies, associated with soil, cutaneous, keratitis, CNS globose usually resistant to accessory polyenes conidia along hyphae A. lentulus Poorly sporulating May be multidrug Invasive pulmonary, variant of A. resistant, recently disseminated, other sites fumigatus described variant, may be underdiagnosed The most common species causing invasive aspergillosis include Aspergillus fumigatus, by far the most common, A. flavus, A. terreus, and, less commonly for invasive infection, A. niger (5) (Table 9.1). Recent studies have shown emergence of less common species, including A. terreus (which is frequently resistant to polyenes) and other unusual less pathogenic species as the etiologic agents of invasive infection (13). 3. EPIDEMIOLOGY The incidence of invasive aspergillosis has increased substantially during the last few decades because of the use of more intensive cytotoxic anticancer chemotherapy and the introduction of novel immunosuppressive therapies for organ transplant recipients, both of which have prolonged the period of risk for many individuals. The increasing number of patients undergoing solid organ, bone marrow, and hematopoietic stem cell

transplantation, and the implementation of aggressive surgical interventions has also 184 Helen W. Boucher and Thomas F. Patterson contributed to the increased incidence (10). The changes in epidemiology of invasive aspergillosis may also be the result of growing awareness of aspergillosis among clini- cians, the introduction of noninvasive diagnostic tools, and improved microbiological laboratory techniques. Invasive fungal infections are an important cause of morbidity and mortality among patients with severely compromised immune systems. Although there have been significant advances in the management of immunosuppressed patients, invasive aspergillosis remains an important life-threatening complication, and is the leading cause of infection-related mortality in many immunocompromised individuals. Immunosuppression and breakdown of anatomical barriers, such as the skin, are the major risk factors for fungal infections (7). Individuals at risk for invasive aspergillosis include those with severely comprised immune systems as a result of anticancer chemotherapy, solid organ or bone marrow transplantation, AIDS, or use of high-dose corticosteroids. Patients with hematological disorders, such as prolonged and severe neutropenia, those undergoing transplantations, and those treated with corticosteroids and newer immunosuppressive therapies such as the tumor necrosis factor- antagonists (e.g., inflixamab) are considered to be at highest risk for invasive aspergillosis (7,14). 4. PATHOGENESIS AND IMMUNITY Invasive aspergillosis most frequently originates via inhalation of Aspergillus conidia into the lungs, although other routes of exposure such as inhalation of water aerosols contaminated with Aspergillus conidia have been suggested (12). In the absence of effective pulmonary host defenses, the inhaled small resting conidia enlarge and germinate, then transform into hyphae with subsequent vascular invasion and eventual disseminated infection. The incubation period for conidial germination in pulmonary tissue is variable, ranging from 2 days to months (15). Hydrocortisone significantly increases the growth rates of Aspergillus; likely one of the reasons corti- costeroids pose a risk factor for invasive disease (16). Although infection in apparently normal hosts can occur, invasive aspergillosis is extremely uncommon in immunocompetent hosts (5). Normal pulmonary defense mechanisms usually contain the organism in a host with intact pulmonary defenses. The first line of defense against Aspergillus is ciliary clearance of the organism from the airways and limited access to the alveoli due to conidia size. This feature is one reason for the increased pathogenicity of A. fumigatus as compared with other species of Aspergillus (16). Once conidia reach the alveoli, pulmonary macrophages are generally capable of ingesting and killing Aspergillus conidia (17). When macrophages fail to kill the conidia (e.g., high fungal inoculum, decreased number or function of macrophages), conidia germinate and begin to form hyphae. Polymorphonuclear leuko- cytes are recruited via complement activation and production of neutrophil chemotactic factors and extracellularly kill both swollen conidia and hyphae (18). Antibodies against Aspergillus are common due to the ubiquitous nature of the organism, although they are not protective nor are they useful in the diagnosis of infection in high-risk patients due to the lack of consistent seroconversion after exposure or infection (19). Corticosteroids play a major role in increasing susceptibility to Aspergillus by decreasing oxidative killing of the organism by pulmonary macrophages and 9. Aspergillosis 185 by increasing the linear growth rate by as much as 30% to 40% and cell synthesis by greater than 150% (16). Many Aspergillus species produce toxins including aflatoxins, ochratoxin A, fumagillin, and gliotoxin. Gliotoxin works in several ways to help evade host defenses: • Inhibition of phagocyte NADPH oxidase activation (key in host defense versus filamentous fungi) • Inhibition of macrophage ingestion of Aspergillus • Suppression of functional T cell responses (9,20) In tissues, invasive aspergillosis causes extensive destruction across tissue planes via vascular invasion with resulting infarction and necrosis of distal tissues. 5. CLINICAL MANIFESTATIONS The clinical syndromes associated with aspergillosis are diverse, ranging from allergic responses to the organism including allergic bronchopulmonary aspergillosis (ABPA), asymptomatic colonization, superficial infection, and acute or subacute and chronic invasive disease. The clinical presentation generally corresponds to the under- lying immune defects and risk factors associated with each patient group, with greater immune suppression correlating with increased risk for invasive disease. Although this chapter focuses on invasive aspergillosis, a brief description of other presenta- tions follows. The reader is encouraged to reference other sources for more in-depth discussion of those conditions (1). 5.1. Allergic Bronchopulmonary Aspergillosis Allergic bronchopulmonary aspergillosis (ABPA) is a chronic allergic response to Aspergillus characterized by transient pulmonary infiltrates due to atelectasis. The incidence of ABPA is estimated to range from 1% to 2% in patients with persistent asthma and in approximately 7% (with a range from 2% to 15%) of patients with cystic fibrosis (21). Specific criteria are used to establish the diagnosis of ABPA as no single finding except for central bronchiectasis in a patient with asthma is diagnostic for the condition (21–23). ABPA typically progresses through a series of remissions and exacerbations but can eventually lead to pulmonary fibrosis, which is associated with a poor long-term prognosis (23). Management of ABPA is directed at reducing acute asthmatic symptoms and avoiding end-stage fibrosis. Corticosteroid therapy is commonly used for treating exacerbations, although few randomized trials have been conducted for their use (24). The role for antifungal therapy was evaluated with a randomized double-blind, placebo-controlled trial that showed itraconazole at 200 mg/day for 16 weeks significantly reduced daily corticosteroid use, reduced levels of immunoglobulin E (IgE), and improved exercise tolerance and pulmonary function (22,25). 5.2. Aspergilloma A pulmonary fungus ball due to Aspergillus or “aspergilloma” is a solid mass of hyphae growing in a previously existing pulmonary cavity, typically in patients with chronic lung disease such as bullous emphysema, sarcoidosis, tuberculosis, histoplas- mosis, congenital cyst, bacterial lung abscess or, very rarely, in a pulmonary bleb 186 Helen W. Boucher and Thomas F. Patterson from Pneumocystis pneumonia in AIDS (26,27). On chest radiograph, a pulmonary aspergilloma appears as a solid round mass in a cavity (see Fig. 5–9, Chapter 5). In many patients the fungus ball due to Aspergillus remains asymptomatic, but in a signif- icant number, hemoptysis occurs and can be fatal (28). Surgical resection is considered the definitive therapy but the dense pleural adhesions adjacent the fungus ball and the poor pulmonary reserve of most patients makes surgery hazardous. Contamination of the pleural space with Aspergillus and the common complication of bronchopleural fistula in the postoperative period can lead to chronic Aspergillus empyema. Dense adhesions make pleural drainage difficult, often requiring pleural stripping or an Eloesser procedure, further compromising lung function (28). Aspergillus can also be associated with fungal balls of the sinuses without tissue invasion (27). The maxillary sinus is the most common site for a sinus aspergilloma to occur (27). Clinical presentation is similar to that for any chronic sinusitis. Management is usually directed at surgical removal and a generous maxillary antrostomy for sinus drainage, along with confirmation that invasive disease has not occurred. 5.3. Other Superficial or Colonizing Syndromes Other superficial or colonizing syndromes of aspergillosis include otomycosis, a condition of superficial colonization typically due to A. niger (29); onychomycosis which, although rare, can become chronic and respond poorly to antifungal agents (30); and keratitis, particularly following trauma or corneal surgery (31). 5.4. Chronic Pulmonary Aspergillosis Denning and colleagues have described three distinct syndromes of chronic pulmonary aspergillosis to better characterize patients who develop chronic pulmonary disease related to Aspergillus (32). These conditions include chronic cavitary pulmonary aspergillosis, which is characterized by the formation and expansion of multiple cavities, which may contain fungus balls, chronic fibrosing aspergillosis, which as its name suggests involves extensive fibrosis, and chronic necrotizing aspergillosis or subacute aspergillosis, in which slowly progressive infection occurs usually in a single thin-walled cavity. In all of these conditions, the diagnosis is suggested by radiological and clinical features and the role for therapy remains specu- lative, although it appears that long-term antifungal therapy may be beneficial in a subset of patients, perhaps even with the extended spectrum triazole antifungals (32,33). 5.5. Invasive Pulmonary Aspergillosis Invasive pulmonary aspergillosis is the most common form of invasive aspergillosis in immunocompromised patients and occurs after approximately 2 weeks of neutropenia (34) or during the course of graft versus host disease, now the most common risk factor in hematopoietic stem cell transplant recipients (35). Symptoms include fever (may be absent in the presence of high-dose corticosteroid therapy), dry cough, shortness of breath, pleuritic chest pain, hemoptysis as well as pulmonary infiltrates all of which lag behind disease progression. In lung transplant patients and those with AIDS, Aspergillus tracheobronchitis can present with cough, wheezing, and shortness of breath and chest radiographs show normal lungs with or without atelectasis (36). 9. Aspergillosis 187 5.6. Disseminated Aspergillosis A variety of signs and symptoms are seen with disseminated invasive aspergillosis according to the organs involved. Involved organs include the kidneys, liver, spleen, and central nervous system (signs and symptoms of stroke or meningitis) most frequently, followed by the heart, bone, skin, and other organs (1). Aspergillosis of the skin can occur either as a manifestation of disseminated disease or by direct extension from a local inoculation, for example, from an intravenous catheter (37). 5.7. Sinusitis Aspergillosis of the sinuses presents in a clinically like rhinocerebral zygomycosis, but is more common in neutropenic patients than in those with diabetic ketoacidosis, and inflammatory signs may thus be less frequent. Fever, nasal congestion, and facial pain can progress to visual changes, proptosis, and chemosis if the infection spreads to the orbit. Posterior extension to the brain can lead to cranial nerve palsies, other focal neurologic deficits, as well as a depressed level of consciousness (38). 5.8. Endocarditis Aspergillus endocarditis is the second most common form of fungal endocarditis after that caused by Candida species and occurs in prosthetic valve recipients and in native cardiac valves in intravenous drug users and patients with indwelling central venous catheters (39). Clinically, these patients present with fever and embolic complications. Blood cultures are rarely positive even with extensive disease (40). 6. DIAGNOSIS Current diagnostic modalities are limited and the clinician must rely on the combi- nation of knowledge of risk factors, a high index of suspicion, clinical judgment, and the finding of fungi in tissue specimens and/or cultures from the presumed site of infection. The diagnosis of proven invasive aspergillosis requires both tissue biopsy demonstrating invasion with hyphae and culture positive for Aspergillus species (41). Aspergillus produce hyaline, 3 to 6 μm wide septate hyphae that typically branch at acute angles (42) (Fig. 9.2). In tissue these features can often distinguish Aspergillus from agents of zygomycosis, but they cannot distinguish Aspergillus from a large number of other opportunistic moulds, including Fusarium and Scedosporium (Pseudallescheria). Thus, culture is needed to confirm the diagnosis (42). Unfortu- nately, invasive, or even less invasive, procedures such as bronchoscopy are often contraindicated in immunosuppressed patients, many of whom have low platelets as a result of chemotherapy and other complications. In this setting, positive culture can support the diagnosis of invasive aspergillosis. Plain chest radiography is of limited utility in invasive aspergillosis, as it has low sensitivity and specificity in this disease6. In contrast, chest computed tomography (CT) scans have proven useful in early diagnosis of invasive pulmonary aspergillosis, as the “halo sign” of low attenuation surrounding a pulmonary nodule has been used successfully as a marker for early initiation of therapy in high-risk patients with neutropenia or who have undergone hematopoietic stem cell transplantation (43–45) (see Fig. 5.8, Chapter 5). Of note, these radiographic findings are also consistent with 188 Helen W. Boucher and Thomas F. Patterson Fig. 9.2. Periodic acid-Schiff (PAS) stained tissue section of lung showing dichotomously branched, septate hyphae of Aspergillus fumigatus. (Courtesy of www.doctorfungus.org). [Figure in color on CD-ROM]. other infections such as Nocardia species, and may increase over the first week of therapy even when the patient is improving; follow-up scans should be ordered and interpreted cautiously with full attention to the clinical progress of the patient (43). Non-culture diagnostic tests have also been used to diagnose aspergillosis and in attempts to preempt difficult to treat proven disease. A sandwich enzyme immunoassay (EIA) that utilizes a monoclonal antibody to Aspergillus galactomannan (Platelia Aspergillus, Sonofi Diagnostics Pasteur, Marnes-la-Coquette, France; BioRad, Redmond, WA) is currently US Food and Drug Administration (FDA)-approved and available and is being used with varying success around the world (46,47). Questions remain regarding the value of routine surveillance testing, frequency of testing, role of false positives, importance of

prior antifungal therapy, and correlation of serum galactomannan results with clinical outcome. Several reports demonstrate the potential for using polymerase chain reaction (PCR) as an early diagnostic marker, which appears more sensitive than other methods including galactomannan (48,49). These assays may be associated with false-positive results due to the ubiquitous nature of Aspergillus conidia, are not standardized, and remain investigational at the present time (50). Other non-culture-based methods for the diagnosis of invasive aspergillosis include detection of the nonspecific fungal marker 1,3--d-glucan using a variation of the Limulus amebocyte assay. This assay (Fungitell™, Associates of Cape Cod, Falmouth, MA) has been approved for diagnostic purposes by the FDA and is a colorimetric assay that can indirectly determine the concentration of 1,3--d-glucan in serum samples (51). The test appears promising as an indicator of infection due to many 9. Aspergillosis 189 Table 9.2 Diagnosis of invasive aspergillosis Diagnostic method Comment Respiratory culture Not frequently positive early in course of infection; positive result in high risk patient (bone marrow transplant, neutropenia) highly correlates with infection; may indicate colonization in other populations (chronic pulmonary diseases, lung transplant) Galactomannan Aspergillus Platelia system (Bio-Rad, Redmond, WA) with variable sensitivity - low (∼40%) with single samples or prior antifungal therapy or prophylaxis; better yield with reduced threshold for positivity, serial samples, testing on BAL samples. False positives with pipercillin–tazobactam, dietary, neonates 1,3--d-glucan Nonspecific detection of cell wall glucan. Commercially available Fungitell™ assay (Associates of Cape Cod, Falmouth, MA), limited validation and availability. PCR Remains investigational due to lack of standardized reagents and methods, both false positives and negatives may occur, some recent studies have suggested less sensitive than other assays Computed tomography In high-risk patient, “halo” sign and/or pulmonary nodules without other documented cause may be a frequent and early sign of invasive pulmonary aspergillosis BAL, bronchoalveolar lavage. fungi, including Aspergillus and Candida but not Cryptococcus or Zygomycetes (which contain little or no -d-glucan). One study suggested the utility of the assay in early diagnosis of invasive fungal infection in a leukemic population, but validation remains limited (52). Diagnosis of invasive aspergillosis is summarized in Table 9.2. 7. TREATMENT The goals of treatment of patients with invasive aspergillosis are to control infection and to reverse any correctable immunosuppression. Patients at high risk of developing invasive aspergillosis should be treated based on clinical or radiological criteria alone if microbiological or histological diagnosis would significantly delay treatment (2). Treatment of Aspergillus infection is challenging due to difficulty in diagnosis, the presence of advanced disease in many by the time of diagnosis and the presence of severe, often irreversible, immunosuppression. Mortality rates are high in patients with invasive aspergillosis and the efficacy of currently available treatments is limited by spectrum of activity and serious toxicity. Treatment failure with currently available antifungal medication in patients with invasive aspergillosis has been reported to be at least 50% (3,4). New antifungal therapies with activity against Aspergillus have been developed, including lipid formulations of amphotericin B, the broad-spectrum triazoles (voriconazole, posaconazole, and ravuconazole), and the echinocandins (caspofungin, 190 Helen W. Boucher and Thomas F. Patterson micafungin, and anidulafungin), all of which offer new options for therapy of this disease (53,54) (Table 9.3). 7.1. Amphotericin B Amphotericin B deoxycholate has been the “gold standard” therapy in patients with invasive aspergillosis for more than 40 years (2). A number of recent studies have consistently documented the limited efficacy and substantial toxicity with Table 9.3 Antifungal agents for treating invasive aspergillosis Agent Typical dose/route of Comments administration Polyene Amphotericin 1.0–1.5 mg/kg IV Prior “gold standard”; associated with significant B daily toxicity and limited efficacy in severely deoxycholate immunosuppressed patients; attempts to reduce toxicity by 24-hour infusions with limited efficacy data and concerns regarding concentration dependent killing (80) Liposomal 3–6 mg/kg IV daily Well tolerated; limited nephrotoxicity or infusion amphotericin related reactions; anecdotal reports of efficacy B with higher doses (7.5 mg/kg per day or more), but limited clinical data (59); indicated for salvage therapy and empirical use (54) Amphotericin 5 mg/kg IV daily Indicated for salvage therapy or intolerance to B lipid standard agents, generally well tolerated (81) complex Amphotericin 3–6 mg/kg IV daily Less nephrotoxic than amphotericin B B colloidal deoxycholate, but associated with more infusion dispersion related and pulmonary toxicity than other lipid formulations (63) Azole Itraconazole 200 mg IV q12h × 4 Erratic bioavailability, improved with oral doses, then 200 mg solution; drug interactions including IV daily or 200 mg chemotherapeutic agents; limited data with PO bid (oral intravenous formulation (2) suspension) Voriconazole 6 mg/kg IV q12 h × Better efficacy and improved survival compared 2 doses, then 4 with amphotericin B deoxycholate; current mg/kg IV q12 h; recommended primary therapy for invasive 200 mg PO bid aspergillosis; drug interactions common, hepatic (step down after 2 toxicity (10–15%) may be dose limiting; visual weeks IV) effects common (∼30%) but not usually dose limited and no long-term toxicity reported (82) 9. Aspergillosis 191 Voriconazole 6 mg/kg IV q12 h × 2 Better efficacy and improved survival compared doses, then 4 mg/kg with amphotericin B deoxycholate; current IV q12 h; 200 mg PO recommended primary therapy for invasive bid (step down after 2 aspergillosis; drug interactions common, hepatic weeks IV) toxicity (10–15%) may be dose limiting; visual effects common ∼30%) but not usually dose limited and no long-term toxicity reported (82) Posaconazole 200 mg PO qid Recent European approval for salvage therapy; loading, 400 PO bid studies in prophylaxis; P450 drug interactions; maintenance; oral limited metabolism with favorable tolerance in solution only clinical studies (83) Ravuconazole Investigational In vitro activity but limited clinical development at present (54) Echinocandin Caspofungin 70 mg × 1 dose, then Indicated for salvage therapy of aspergillosis, 50 mg IV daily experimental and clinical data for use in combination therapy; well tolerated (69) Micafungin Investigational for Used in doses of 100 mg/day in salvage studies; aspergillosis (IV) 50 mg/day for prophylaxis; well tolerated (72) Anidulafungin Investigational for In vitro activity; studied at doses of 100 mg/day in aspergillosis (IV) other fungi; well tolerated (84) IV, intravenous; PO, orally; bid, twice daily; qid, four times daily. amphotericin B deoxycholate in high-risk patients (44,55,56). The overall response rates of amphotericin B deoxycholate are less than 25%, with responses of only 10% to 15% in more severely immunosuppressed patients (5,44). Wingard and colleagues recently documented increased morbidity and mortality associated with conventional amphotericin B (amphotericin B deoxycholate) in patients receiving bone marrow trans- plantation and those receiving concomitant nephrotoxic agents (56). Similar finding were documented by Bates and colleagues, who found that renal toxicity occurred in approximately 30% of patients receiving conventional amphotericin B and that this toxicity was associated with a sixfold increase in mortality as well as a dramatic increase in hospital costs (55). These unacceptably high mortality rates and significant toxicities have highlighted the need for new therapeutic approaches in this disease, so that for most patients with invasive aspergillosis, primary therapy with amphotericin B can no longer be recommended (57). The lipid formulations of amphotericin B were developed to decrease toxicity and allow the administration of higher doses of drug (58,59). To date, few comparative studies of the efficacy of lipid formulations of amphotericin B in treating invasive aspergillosis have been conducted, although studies of these drugs as salvage therapy led to the approval of three lipid formulations (60). Clinical experience has nevertheless been favorable, which is consistent with preclinical studies in animal models (61). One small study by Leenders and colleagues compared liposomal amphotericin B at 5 mg/kg per day to standard amphotericin B at 1.0 mg/kg day for proven or suspected invasive mycoses (62). Overall outcomes of both groups in this small study were 192 Helen W. Boucher and Thomas F. Patterson similar, but analysis of patients with proven invasive aspergillosis favored the lipid preparation of amphotericin B. A recent study evaluated amphotericin B colloidal dispersion for primary therapy for invasive aspergillosis (63). In this study of severely immunosuppressed patients with invasive aspergillosis, success rates with the lipid formulation were not better than those for conventional amphotericin B, although toxicity was minimally decreased. These results suggest that although lipid formulations of amphotericin B are dramatically more expensive than standard amphotericin B, hidden costs of standard amphotericin B in terms of morbidity and mortality as well as resource utilization may justify the use of lipid formulation of amphotericin B in certain high-risk patients (55). 7.2. Azoles Voriconazole is a potent, broad-spectrum, triazole that has cidal activity against many Aspergillus species, including A. terreus; is approved for therapy of invasive aspergillosis; and has become the recommended primary therapy for most patients with invasive aspergillosis (53,64). This recommendation is based on data from a randomized trial that compared voriconazole to conventional amphotericin B for the primary treatment of invasive aspergillosis, with each agent followed by other licensed antifungal therapy if needed for intolerance or progression of disease, in severely immunocompromised patients with invasive aspergillosis (44). In this trial, voriconazole was superior to amphotericin B, with successful outcomes in 52% of patients as compared to only 31% in those receiving amphotericin B. In addition, voriconazole demonstrated a survival advantage to amphotericin B, with an absolute 13% difference in mortality between treatment groups. In clinical trials, voriconazole has been adequately tolerated and the drug exhibits a favorable pharmacokinetic profile. There are a number of issues to consider, including important drug interactions, especially those with immunosuppressive agents such as cyclosporine, tacrolimus, and sirolimus, the latter of which is contraindicated for use with voriconazole, and intolerance to the drug. The most common adverse event has been a transient and reversible visual disturbance described as an altered perception of light which has been reported in approximately 30% of treated patients, but has not been associated with pathologic changes (44). Other less frequently reported adverse events include liver function test abnormalities in 10% to 15%, and skin rash in 6% (sometimes associated with sun exposure). Among the other azole antifungal agents, itraconazole is approved for use as salvage therapy of aspergillosis. Its utility has been limited because until recently it has been available only in an oral formulation that is poorly absorbed; drug interactions further complicate use of this agent. An intravenous formulation of itraconazole has only recently been approved for up to 2 weeks of clinical use (65). For these reasons, itraconazole is more frequently used in less immunosuppressed patients who are able to take oral therapy and for use as sequential oral therapy (5). Other second-generation triazoles, including posaconazole and ravuconazole, were developed with an expanded spectrum of activity to include Aspergillus (64,66). Posaconazole is available in only an oral formulation, has demonstrated in vitro and in vivo activity against Aspergillus, and has shown clinical activity in an open-label trial which led to its 2005 approval 9. Aspergillosis 193 in the EU for salvage therapy of invasive aspergillosis (67). Ravuconazole has been evaluated in early phase clinical trails and has also shown activity in animal models of invasive aspergillosis (68). 7.3. Echinocandins Echinocandins are natural cyclic hexapeptide antifungal compounds that noncom- petitively inhibit 1,3--d-glucan synthase, an enzyme complex that is unique to a number of fungi, which forms glucan polymers in the fungal cell wall (54). These agents are active against Candida species and Pneumocystis. Specific modifications to the N-acyl aliphatic or aryl side chains expand the antifungal spectrum to include Aspergillus (54). These agents are all poorly bioavailable and produced in intravenous formulation only. Caspofungin is approved for treating patients refractory to or intolerant of standard therapies for invasive aspergillosis based on an open-label trial that demonstrated therapeutic efficacy in 22 of 54 (41%) patients studied (69). Caspofungin has been very well tolerated in clinical trials; in the aspergillosis study, only approximately 5% of patients discontinued therapy. Drug interactions with cyclosporine may occur, but have not been a significant issue (69,70). In March 2005, micafungin was approved for the treatment of esophageal candidiasis and prevention of Candida infections. In the one prophylaxis study used to support this approval, micafungin may have reduced the number of Aspergillus infections as compared to standard prophylaxis with fluconazole (71). Micafungin also demonstrated efficacy when used as salvage therapy (72). Anidulafungin is another echinocandin with activity against Aspergillus spp. that appears to have a favorable toxicity profile similar to the other echinocandins. It was approved by the

FDA in February 2006 for candidemia and other Candida infections (including abdominal abscess, peritonitis, and esophagitis). Notably, these agents are neither classically fungicidal nor fungistatic for Aspergillus, but exert their effect on the growing hyphal tips where the glucan synthase target is located (73). For this reason, they have not frequently been used for primary therapy and have been more frequently used as salvage therapy or more recently in combination regimens (74,75). 7.4. Other Therapies and Therapeutic Approaches Outcomes for patients with invasive aspergillosis remain poor despite the advent of newer antifungal agents. This, together with the availability of several antifungal drugs and drug classes against Aspergillus, has increased interest in combination antifungal therapy for this infection (76,77). Marr and colleagues reported on a historical control study of caspofungin and voriconazole compared with voriconazole alone in patients who failed amphotericin formulations in 2004. In this study, the use of combination salvage therapy was associated with an improved 3-month survival rate and the authors conclude that further studies of this strategy are warranted (75). Adjuvant therapies including surgical resection or use of granulocyte transfusions and growth factors in invasive aspergillosis can augment antifungal therapy, although their utility has not been established in randomized trials. Surgical resection of isolated pulmonary nodules prior to additional immunosuppressive therapies has been shown to improve outcome of 194 Helen W. Boucher and Thomas F. Patterson infection (6,78). Recent studies suggest that the majority of patients will have bilateral infection when the diagnosis is first made, limiting the utility of this approach. Surgical resection may also be indicated in patients with severe hemoptysis or lesions near the hilar vessels or pericardium. The guidelines for treating invasive aspergillosis published by the Infectious Diseases Society of America were produced before the introduction of the newest available agents; a revised document is currently in press (2). Unfortunately, few randomized, controlled trials exist to be used to formulate specific guidelines for therapy. A prompt diagnosis and aggressive initial therapy are both critical in improving the outcome of this infection (79). Radiography and use of galactomannan EIA may facilitate an early detection of aspergillosis in high risk patients, for whom outcomes are especially poor (45). Most patients should receive primary therapy with voriconazole, which has been shown to be superior to amphotericin B, the other agent approved for primary therapy of this infection (44). However, in patients who are intolerant of voriconazole, have a contraindication to the drug, or have progressive infection, alternative agents include lipid formulations of amphotericin B, the echinocandins, or another triazole (58,61,69). Primary use of combination therapy is not recommended at the present time because of lack of prospective clinical trial data, but the addition of another agent in a salvage setting may be considered, owing to the poor outcomes of a single agent in progressive infection (75). Sequential therapy with oral azoles after initial intravenous therapy may be a useful option (5). Although the optimal duration of antifungal therapy is not known, improvement in underlying host defenses is crucial to successful therapy. 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Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J Clin Oncol 2001;19:253–259. 44. Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408–415. 45. Herbrecht R. Improving the outcome of invasive aspergillosis: new diagnostic tools and new therapeutic strategies. Ann Hematol 2002;81 (Suppl 2):S52–S53. 46. Maertens J, Theunissen K, Verbeken E, et al. Prospective clinical evaluation of lower cut- offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients. Br J Haematol 2004;126:852–860. 47. Maertens J, Theunissen K, Verhoef G, et al. Galactomannan and computed tomography- based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. 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Multicenter clinical evaluation of the (1–>3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 2005;41:654–659. 53. Steinbach WJ, Stevens DA. Review of newer antifungal and immunomodulatory strategies for invasive aspergillosis. Clin Infect Dis 2003;37 (Suppl 3):S157–S187. 54. Boucher HW, Groll AH, Chiou CC, Walsh TJ. Newer systemic antifungal agents: pharma- cokinetics, safety and efficacy. Drugs 2004;64:1997–2020. 55. Bates DW, Su L, Yu DT, et al. Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin Infect Dis 2001;32:686–693. 56. Wingard JR, Kubilis P, Lee L, et al. Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis. Clin Infect Dis 1999;29:1402–1407. 57. Ostrosky-Zeichner L, Marr KA, Rex JH, Cohen SH. Amphotericin B: time for a new “gold standard.” Clin Infect Dis 2003;37:415–425. 58. Walsh TJ, Hiemenz JW, Seibel NL, et al. 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Agents Chemother 2001;45:3487–3496. 60. Rex JH, Walsh TJ, Nettleman M, et al. Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses. Clin Infect Dis 2001;33:95–106. 61. Barrett JP, Vardulaki KA, Conlon C, et al. A systematic review of the antifungal effec- tiveness and tolerability of amphotericin B formulations. Clin Ther 2003;25:1295–1320. 62. Leenders AC, Daenen S, Jansen RL, et al. Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia- associated invasive fungal infections. Br J Haematol 1998;103:205–212. 63. Bowden R, Chandrasekar P, White MH, et al. A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin Infect Dis 2002;35:359–366. 64. Espinel-Ingroff A, Boyle K, Sheehan DJ. In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: review of the literature. Mycopathologia 2001;150:101–115. 65. Caillot D. Intravenous itraconazole followed by oral itraconazole for the treatment of amphotericin-B-refractory invasive pulmonary aspergillosis. Acta Haematol 2003;109:111–118. 66. Sheehan DJ, Hitchcock CA, Sibley CM. Current and emerging azole antifungal agents. Clin Microbiol Rev 1999;12:40–79. 198 Helen W. Boucher and Thomas F. Patterson 67. Raad I, Chapman S, Bradsher R. Posaconazole (POS) salvage therapy for invasive fungal infections (IFI) (abstract M-699), 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2004. 68. Kirkpatrick WR, Perea S, Coco BJ, Patterson TF. Efficacy of ravuconazole (BMS- 207147) in a guinea pig model of disseminated aspergillosis. J Antimicrob Chemother 2002;49:353–357. 69. Maertens J, Raad I, Petrikkos G, et al. 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Antimicrob Agents Chemother 2002;46:3001–3012. 74. Kirkpatrick WR, Perea S, Coco BJ, Patterson TF. Efficacy of caspofungin alone and in combination with voriconazole in a Guinea pig model of invasive aspergillosis. Antimicrob Agents Chemother 2002;46:2564–2568. 75. Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis 2004;39:797–802. 76. Kontoyiannis DP, Hachem R, Lewis RE, et al. Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer 2003;98:292–299. 77. Aliff TB, Maslak PG, Jurcic JG, et al. Refractory Aspergillus pneumonia in patients with acute leukemia: successful therapy with combination caspofungin and liposomal amphotericin. Cancer 2003;97:1025–1032. 78. Yeghen T, Kibbler CC, Prentice HG, et al. Management of invasive pulmonary aspergillosis in hematology patients: a review of 87 consecutive cases at a single institution. Clin Infect Dis 2000;31:859–868. 79. Patterson TF, Boucher HW, Herbrecht R, et al. Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome. Clin Infect Dis 2005;41:1448–1452. 80. Imhof A, Walter RB, Schaffner A. Continuous infusion of escalated doses of amphotericin B deoxycholate: an open-label observational study. Clin Infect Dis 2003;36:943–951. 81. Wingard JR, White MH, Anaissie E, Raffalli J, Goodman J, Arrieta A. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis 2000;31:1155–1163. 82. Keating GM. Posaconazole. Drugs 2005;65:1553–1567. 83. Murdoch D, Plosker GL. Anidulafungin. Drugs 2004;64:2249–2258. 84. Johnson LB, Kauffman CA. Voriconazole: a new triazole antifungal agent. Clin Infect Dis 2003;36:630–637. 9. Aspergillosis 199 SUGGESTED READINGS Boucher HW, Groll AH, Chiou CC, Walsh TJ. Newer systemic antifungal agents: pharmacoki- netics, safety and efficacy. Drugs 2004;64:1997–2020. Caillot D, Casasnovas O, Bernard A, et al. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol 1997;15:139–147. Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408–415. Keating GM. Posaconazole. Drugs 2005;65:1553–1567. Patterson TF. Aspergillus species. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Philadelphia: Elsevier Churchill Livingstone, 2005;2958–2973. Patterson TF. Advances and challenges in management of invasive mycoses. Lancet 2005; 366:1013–1025. Patterson TF, Kirkpatrick WR, White M, et al. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. Medicine (Baltimore) 2000;79:250–260. Maertens J, Theunissen K, Verhoef G, et al. Galactomannan and computed tomography- based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis 2005;41:1242–1250. Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis 2004;39:797–802. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guide- lines of the Infectious Diseases Society of America (IDSA). Clin Infect Dis (In press). Walsh TJ, Petraitis V, Petraitiene R, et al. Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B. J Infect Dis 2003;188:305–319. 10 Hyalohyphomycosis—Infection Due to Hyaline Moulds Rhonda V. Fleming, MD and Elias J. Anaissie, MD 1. INTRODUCTION Hyalohyphomycosis is the term used to designate infections caused by fungi noted to have hyaline (colorless) septate hyphae microscopically in clinical samples, similar to the use of phaeohyphomycosis for those infections caused by pigmented fungi (Chapter 11). This distinction is clinically useful when hyphal elements are seen on tissue examination but fail to grow. Hyalohyphomycosis typically includes infections caused by species of Fusarium, Scedosporium, Acremonium, Paecilomyces, Scopulariopsis, Beauveria, and Penicillium. Although Aspergillus produces similar hyaline septate hyphae microscopi- cally, and is thus considered a member of this grouping of fungi, infection caused by this genus (aspergillosis) is generally discussed as a separate disease (Chapter 9). These agents may cause superficial or localized infection in immunocompetent hosts (usually as a result of direct inoculation of the fungus after trauma) and invasive or disseminated infections in immunocompromised hosts. In the latter setting, the clinical infection may be indis- tinguishable from that of invasive aspergillosis. A remarkable feature of some of these hyaline moulds is their ability to cause fungemia and to disseminate hematogenously, causing numerous embolic skin lesions. These infections may be clinically suspected on thebasisofaconstellationofclinicaland laboratoryfindings.Definitivediagnosis requires isolation of the organism because histopathological examination reveals branching hyaline septate hyphae regardless of the pathogen, similar to the findings with Aspergillus. Anaccuratediagnosisat thespecies level is importantbecauseof thevariablesusceptibility to antifungal agents. An important component of therapy of localized infection is surgery and removal of infected prosthetic devices. Outcome is usually favorable in immuno- competent hosts, while usually very poor in the setting of persistent profound immuno- suppression. We herein describe the most relevant characteristics of these organisms and the clinical spectrum and diagnosis and treatment of infections caused by these agents. From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 201 202 Rhonda V. Fleming and Elias J. Anaissie 2. FUSARIUM 2.1. Introduction Fusarium species recently emerged as a cause of disseminated infections in neutropenic patients and in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Fusarium represents the second most common fungal pathogen, after Aspergillus, as the cause of life-threatening infection in recipients of hematopoietic transplant (1). Fusarium causes a broad spectrum of infections in humans, including superficial and local infections in immunocompetent hosts, while disseminated infection is seen almost exclusively in immunosuppressed patients. 2.2. Etiologic Agents Four species are most commonly involved in human infections: F. solani (the most common), F. oxysporum, F. moniliforme, and F. proliferatum (2). Fusarium species are septate filamentous fungi that produce conidiophores, phialides, macroconidia, and microconidia. Fusarium species grow easily and rapidly in almost all fungal media. On potato dextrose agar (PDA), the colonies have a velvety or cottony surface, and are white, yellow, pink, purple salmon or gray on the surface, with a pale, red, violet, brown or sometimes blue reverse. The characteristic sickle- or banana-shaped multiseptate macroconidia with a foot cell at the base are used in identifying the genus and species of Fusarium (Fig. 10.1). Molecular methods may also be used for rapid identification of Fusarium to the species level. In tissue, the hyphae are similar to those of Aspergillus species, with hyaline and septate filaments that typically dichotomize in acute and right angles. In the absence of microbial growth, distinguishing fusariosis from aspergillosis and other hyalohyphomycoses is difficult, and requires the use of in situ hybridization in paraffin-embedded tissue specimens (3). Fusarium species are toxigenic, and may cause mycotoxicosis in animals and humans (2). 2.3. Epidemiology Fusarium is ubiquitous in soil and water, taking part in water biofilms and is a human and plant pathogen (4). Fusarium species are causative agents of superficial and localized infections in immunocompetent hosts, most commonly onychomycosis and cutaneous and subcutaneous infections including mycetoma and keratitis, the latter in contact lens wearers (5). A recent large outbreak of Fusarium keratitis was reported in contact lens wearers in the United States and was linked to contaminated contact lens rinse solutions (6). Other risk factors for keratitis are trauma and use of topical corticosteroids and antibiotics. Fusarium endophthalmitis may arise from keratitis or by direct inoculation after cataract surgery or trauma (7). Fusariosis may also result from skin breakdown, such as burns and wounds, or the presence of foreign bodies, such as peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD), and catheter-associated fungemia, and thrombophlebitis (8–10). Other infections include sinusitis, pneumonia, cutaneous and subcutaneous infections, septic arthritis, and osteomyelitis (11–15). Immunosuppressed patients may develop locally invasive and disseminated fusar- iosis (16). Risk factors include prolonged neutropenia such as following chemotherapy 10. Hyalohyphomycosis—Infection Due to Hyaline Moulds 203 Fig. 10.1. Fusarium oxysporum macroconidia. Characteristic fusiform to sickle-shaped, multiseptate, mostly with an attenuated apical cell and a foot-shaped basal cell. (Courtesy of www.doctorfungus.org.) [Figure in color on CD-ROM]. for acute leukemia and T-cell immunodeficiency which occurs most commonly after HSCT (16–18). In HSCT infection may develop early during neutropenia or months after neutrophil recovery, following treatment of chronic extensive graft versus host disease (GvHD). Localized infections may also develop among solid organ transplant recipients (SOT), usually as a late infection (19). Portals of entry are the respiratory tract and skin, the latter playing a significant role in patients with tissue breakdown such as onychomycosis. Hospital water systems are a potential reservoir for Fusarium; transmission may occur from inhalation of conidia aerosolized in the shower or from direct contact of contaminated water with sites of skin breakdown (20–22). 2.4. Pathogenesis and Immunology Similar to Aspergillus, this organism is highly angioinvasive and leads to tissue infarction. In contrast to Aspergillus however, Fusarium is frequently isolated from the bloodstream, likely as a result of intravascular adventitious sporulation (23). Phagocytes appear to be the predominant line of defense against fusarial infections (16–18). 2.5. Clinical Manifestations Infection with Fusarium in immunocompetent hosts may be superficial or locally invasive, involving the skin, eyes, sinuses, lungs, and joints and bones. In immuno- suppressed patients, the infection may be locally invasive, usually pneumonia and/or sinusitis, or more commonly disseminated (16–18). The clinical picture resembles that of invasive aspergillosis. Unlike aspergillosis, however, fungemia and skin lesions are common (up to 40% of patients with disseminated disease). Skin lesions may represent 204 Rhonda V. Fleming and Elias J. Anaissie the primary site of infection (onychomycosis) or secondary to disseminated infection (16–18). Metastatic skin lesions evolve from subcutaneous painful lesions, to erythe- matous induration followed by ecthyma gangrenosum-like with necrotic center, which may be surrounded by a rim of erythema (16–18). 2.6. Diagnosis Two characteristics suggest the diagnosis of disseminated fusariosis in the severely immunocompromised host: metastatic skin lesions and positive blood cultures for

mould (16–18). Definitive diagnosis relies on cultures (tissue and/or blood) and histopathology which shows a pattern common to all hyalohyphomycosis (invasion by acute-branching, septate hyaline hyphae). The use of polymerase chain reaction (PCR) techniques and/or in situ hybridization may be required to reach the correct diagnosis in tissues (3,24). The 1,3--d-glucan test is usually positive in invasive fusarial infections, but it cannot distinguish Fusarium from other fungal infections (Candida, Aspergillus, Trichosporon and others) that are also detected by the assay (25). 2.7. Treatment Localized infections, particularly in immunocompetent hosts, usually respond well to treatment consisting of topical therapy for fungal keratitis or excision of involved tissue (sinuses, eye, soft tissue, bone). Removal of an infected intravascular catheter may be needed in the rare cases of catheter-related fungemia. The outcome of disseminated fusariosis in severely immunosuppressed patients remains poor despite aggressive antifungal therapy, with very high mortality rates (16–18). Predictors of poor outcome are persistent neutropenia and recent therapy with corticosteroids for chronic GvHD (17). Treatment options are limited by the lack of reliable and consistent activity of antifungal agents against Fusarium species. F. moniliforme is the most susceptible species, typically inhibited by amphotericin B and the newer triazoles voriconazole and posaconazole; F. verticilloides is commonly resistant to both antifungal classes. F. solani and F. oxysporum have an interme- diate susceptibility to amphotericin B, but are resistant to the triazoles (26). Hence, rapid species identification is needed and antifungal susceptibility testing should be considered because of this variable in vitro susceptibility among Fusarium species (Table 10.1). The echinocandins do not appear to be active against Fusarium. 3. SCEDOSPORIUM 3.1. Introduction Two Scedosporium species, S. apiospermum (sexual state name, Pseudallescheria boydii) and S. prolificans (formerly S. inflatum) cause human disease (27,28). A spectrum of disease, ranging from respiratory tract colonization (cystic fibrosis or SOT) to superficial and deep infections, in both immunocompetent and immunosuppressed hosts, has been reported. Rarely, disseminated infection with high mortality is seen in the setting of severe immunosuppression. S. prolificans belongs to the group of fungi that cause phaeohyphomycosis (dematiaceous fungi), but are briefly discussed because of its relationship to S. apiospermum . Table 10.1 Overall susceptibility of hyaline fungi to available antifungalsa Genus/species AmB Itraconazole Voriconazole Posaconazole Anidulafungin Caspofungin Ref. Fusarium spp. ++ + ++b ++ 0 0 (50,51) F. oxysporum ++ + ++++ ++ ND ND (50,52) F. solani + + + + ND ND Scedosporium spp. S. prolificans 0 0 0 0 0 ND (51) S. apiospermum 0 ++ ++++ +++ 0 0 (51,52) Paecilomyces spp. ++ +++ +++ +++ ++ +++ (50,51) Acremonium spp. ++ 0 ++ ND 0 ND (51) ++++, drug of choice; +++, alternative choice; ++, some strains are susceptible (< 50%); +, rarely susceptible (< 10%); 0, always resistant; ND, no data available. aSusceptibility based on MIC50. bIn the United States, the only agent indicated for invasive fusariosis. 206 Rhonda V. Fleming and Elias J. Anaissie 3.2. Etiologic Agents Scedosporium species are identified by their characteristic macroscopic (wooly to cottony, dark gray to dark brown) and microscopic (characteristic conidia, conidio- phores, and hyphae) appearance. S. prolificans is distinguished from S. apiospermum by the production of terminal annelloconidia with inflated bases (cylindrical in S. apiospermum) and growth inhibition by cycloheximide or actidione. In tissue sections, Scedosporium appear as septate hyaline hyphae that cannot be reliably distin- guished from Aspergillus or Fusarium unless conidia are present. 3.3. Epidemiology Scedosporium have been isolated from soil, potting mix, compost, and animal manure and stagnant or polluted water. Infections occur worldwide, though a large number of reports come from Northern Spain (27). Patients at risk for invasive and/or disseminated infection include those with human immunodeficiency virus (HIV) infection, acute leukemia and recipients of allogeneic HSCT or SOT (29,30). Infection is thought to be secondary to direct inoculation (such as after trauma) or inhalation of airborne conidia. In normal hosts, S. apiospermum causes infection after penetrating trauma, including keratitis, endophthalmitis, cutaneous and subcutaneous infections, bursitis, arthritis, and osteomyelitis. After near drowning accidents, sinusitis, pneumonia, meningoencephalitis, and brain abscesses may develop. Allergic bronchopulmonary disease due to S. apiospermum may also occur. Like S. apiospermum, S. prolificans causes localized infections (usually of bone or soft tissue) in immunocompetent patients after trauma, and deeply invasive infections in immuno- compromised hosts, sometimes as a nosocomial outbreak (27,29,30). 3.4. Clinical Manifestations Mycetoma is the most common S. apiospermum infection in normal hosts (see Chapter 21), usually occurring after penetrating injury and presenting as lower extremity swelling with draining sinuses. Other infections include non-mycetoma cutaneous and subcutaneous infections, keratitis, and endophthalmitis (29). Invasive S. apiospermum infection is usually seen in immunocompromised patients, most commonly as pneumonia. Disseminated infection is mainly associated with S. prolif- icans, and is characterized by refractory fever, pulmonary infiltrates (diffuse or nodular), central nervous system involvement (present in one third of patients), fungemia, renal failure and erythematous, and nodular skin lesions with central necrosis. 3.5. Diagnosis The diagnosis relies on the combination of clinical signs and symptoms and recovery of Scedosporium from blood and/or infected tissue, with or without demonstration of colorless septate hyphae. 3.6. Treatment Localized infections, particularly in immunocompetent hosts, usually respond well to surgical débridement. Scedosporium apiospermum is resistant to fluconazole and flucytosine, but susceptible to the newer azoles voriconazole, posaconazole, and 10. Hyalohyphomycosis—Infection Due to Hyaline Moulds 207 ravuconazole (Table 10.1). Voriconazole is approved for use in S. apiospermum infec- tions (31,32). Caspofungin appears to be more active than itraconazole or amphotericin B. Variable strain-to-strain susceptibility to amphotericin B can be seen (33). Surgical resection remains the only definite therapy for S. prolificans infections, as this organism is resistant to all available antifungal agents in vitro. In vitro synergism between terbinafine and either voriconazole or itraconazole has been reported (34). 4. PAECILOMYCES 4.1. Introduction Paecilomyces species are frequent airborne contaminants in clinical microbiology laboratories but have been increasingly reported as cause of human infection. 4.2. Etiologic Agents Two Paecilomyces species, P. lilacinus (most common) and P. varioti, account for most human infections; although recent reports have described infection secondary to P. marquandii and P. javanicus. Paecilomyces grow rapidly on various agar media including blood, chocolate, Sabouraud dextrose (SDA), and PDA. P. varioti is thermophilic and grows well at temperatures as high as 50°C. The color of the colony and certain microscopic features help differentiate Paecilomyces species from each other. The colonies are flat and velvety. The color is initially white and becomes yellow-green, yellow-brown, pink or violet according to species. 4.3. Epidemiology Paecilomyces are found worldwide in soil, food products, and water and causes infection in both immunocompetent and immunosuppressed patients. A strong associ- ation of Paecilomyces with prosthetic implants may be due to their inherent resistance to most sterilizing techniques. Prosthetic implant-related infections include keratitis in contact lens wearers and after corneal implants (rarely endophthalmitis), and in recipients of CAPD, cardiac valves, and ventriculoperitoneal shunts. Other infections involve the nails, skin, and subcutaneous tissues, bones and joints, sinuses and lungs, while disseminated infections only occur in immunosuppressed patients (35). 4.4. Clinical Manifestations The most common infections due to Paecilomyces involve the eye and eye struc- tures (keratitis and endophthalmitis), followed by the nails (onychomycosis) and skin and soft tissues. Skin infections are characterized by erythematous macules, nodules, pustules, vesicular lesions, or necrotic crusts (35). Sporotrichosis-like skin infection has also been described. Other reported infections in the competent host include peritonitis in CAPD, prosthetic-valve endocarditis, catheter-related fungemia, and arthritis/osteomyelitis. In immunocompromised patients, pneumonia and disseminated disease are most commonly observed. 4.5. Diagnosis Paecilomyces infections are diagnosed with routine tissue culture. These organisms are easily cultured on SDA and on histopathology, hyaline septate hyphae can be seen 208 Rhonda V. Fleming and Elias J. Anaissie with periodic acid-Schiff (PAS) staining. Paecilomyces may exist in various forms in tissue (conidia and phialides) and can therefore be misdiagnosed as candidiasis. 4.6. Treatment Treatment of invasive Paecilomyces infections relies on surgical debridement and removal of infected prosthetic materials. Because of different susceptibilities to antifungal agents, Paecilomyces should be identified to the species level (Table 10.1). P. varioti is susceptible to amphotericin B, flucytosine, itraconazole, voriconazole, and posaconazole, whereas P. lilacinus is susceptible only to the latter two triazoles (36). 5. ACREMONIUM 5.1. Introduction Acremonium species are filamentous fungi of low pathogenicity commonly isolated from the environment (soil, insects, sewage, plants, and water) (37). 5.2. Etiologic Agents Seven species of Acremonium have been reported to cause human infection with more than 80% of infections caused by A. strictum (the most common), A. falciforme, A. recifei, and A. kiliense. Acremonium species grow on SDA, forming white, salmon, or yellowish-green colonies that are usually velvety or cottony with slightly raised centers. This genus is distinguished by formation of narrow hyphae bearing solitary, unbranched needle-shaped phialides. As in other hyaline moulds, septate colorless hyphae are found in tissue. 5.3. Epidemiology Most infections occur in immunocompetent hosts and include mycetoma following trauma, keratitis in contact lenses wearers, and endophthalmitis (37–39). Fungal colonization of humidifier water in a ventilator system was thought to be the source of infections in an outbreak of endophthalmitis. Invasive disease is almost exclusively seen in immunocompromised patients. 5.4. Clinical Manifestations Mycetoma is the most common infection due to Acremonium and presents in a manner similar to that of mycetoma caused by S. apiospermum. Keratitis and endophthalmitis constitute the second most common infections. Colonization of soft contact lenses may proceed to corneal invasion. Other reported infections include onychomycosis, peritonitis, dialysis fistulae infection, pneumonia, empyema, septic arthritis, osteomyelitis, meningitis (following spinal anesthesia in an otherwise healthy individual), cerebritis in an intravenous drug abuser, and prosthetic valve endocarditis. Disseminated infection occurs exclusively in immunosuppressed hosts and has been characterized by endocarditis, meningitis, and bloodstream infection. In vivo sporu- lation can occur, facilitating dissemination and perhaps explaining the high rate of metastatic skin lesions and positive blood cultures with Acremonium. 10. Hyalohyphomycosis—Infection Due to Hyaline Moulds 209 5.5. Diagnosis Acremonium species grow slowly on SDA. Hence, cultures must be kept at least 2 weeks. Blood cultures may isolate Acremonium in cases of disseminated disease. Like other hyaline moulds, septate colorless hyphae are found in histopathologic examination that stain with PAS (39). Acremonium may be difficult to identify in tissue because of morphologic similarities with other moulds, such as Fusarium. 5.6. Treatment Acremonium species have a variable susceptibility to antifungal agents (37) (Table 10.1). In vitro activity of amphotericin B and itraconazole against Acremonium is variable, while resistance to fluconazole and 5-fluorocytosine is uniform. The newer azoles, voriconazole and posaconazole, appear promising. 6. PENICILLIUM MARNEFFEI 6.1. Introduction Most Penicillium species are frequent laboratories contaminants, but P. marneffei has emerged as a significant pathogen, and can cause disseminated infection in HIV- infected patients residing or traveling to Southeast Asia where the disease is endemic (40). 6.2. Etiologic Agents Penicillium marneffei is a facultative intracellular pathogen and the only known thermally dimorphic fungus of the genus Penicillium. At room temperature, P. marneffei exhibits the characteristic morphology of the genus; in contrast, it grows as a yeast when found in infected tissue or at 37°C. 6.3. Epidemiology Infection due to Penicillium marneffei constitutes the third most common oppor- tunistic infection in HIV-infected patients in certain parts of Southeast Asia and is endemic in the Guangxi province of China, Hong Kong, and Taiwan (41). The incidence of penicilliosis has increased significantly, paralleling the incidence of HIV infection. Although penicilliosis is most commonly seen in adults infected with HIV, the disease has also been detected in children and adults without immunodeficiency. The mode of transmission is thought to be due to ingestion or inhalation of the fungus. Soil exposure, especially during rainy season, has been suggested to be a critical factor. 6.4. Clinical Manifestations Penicilliosis marneffei can clinically resemble tuberculosis, molluscum contagiosum, cryptococcosis, and histoplasmosis. The most common clinical manifestation in penicil- liosis includes low-grade fever, anemia, weight loss, cough, lymphadenopathy, and hepatosplenomegaly (42–44). Skin lesions are present in up 70% of the cases and are characterized by a central necrotic umbilication resembling molluscum contagiosum. Palatal and pharyngeal lesions can also be present. Bloodstream infection is present in approximately 50% of cases. Pulmonary involvement has been described as being 210 Rhonda V. Fleming and Elias J. Anaissie diffuse or focal with either a reticulonodular or alveolar pattern. The mean number of CD4+ T lymphocytes at presentation is

64 cells/μl(41). 6.5. Diagnosis Diagnosis of P. marneffei infections is usually made by identification of the organism from smear, culture, or histopathologic sections. Rapid diagnosis of suspected infection could be obtained by direct examination of bone marrow aspirate, lymph node, or skin biopsy. Microscopic examination of Wright-stained smears reveal yeasts forms both within phagocytes and extracellularly. The intracellular forms resemble those seen with Histoplasma capsulatum infection. The demonstration of characteristic central septation and elongated “sausage-shaped” forms by methenamine silver stain, clearly distinguish P. marneffei from H. capsulatum (see Fig. 3.7, Chapter 3). 6.6. Treatment Penicillium marneffei is usually susceptible to both amphotericin B and the azole antifungals. Amphotericin B is effective in the majority of the cases, whereas the azoles are preferred for mild to moderate infections. In a nonrandomized trial of 74 HIV- infected patients with disseminated penicilliosis (45), high response rate (97%) was demonstrated with a regimen of amphotericin B (0.6 mg/k per day) for 2 weeks, followed by itraconazole (400 mg/day) for 10 weeks. Relapse is common 6 months after discontinuation of therapy, as high as 50% in patients who do not receive mainte- nance antifungal therapy. Long-term suppressive therapy with itraconazole has been recommended in patients with HIV infection and penicilliosis (46). Recent noncon- trolled trials, however, demonstrated safe discontinuation of secondary prophylaxis for penicilliosis in HIV-infected patients who were responding to highly active anti- retroviral therapy (HAART) (42,47). 7. OTHER AGENTS OF HYALOHYPHOMYCOSIS Scopulariopsis species are common soil saprophytes and have been isolated worldwide (see Fig. 2.12, Chapter 2). Five species have been associated with human infections: S. brevicaulis, S. brumptii, S. acremonium, S. fusca, and S. koningii. Disease in immunocompetent hosts include onychomycosis (most common), keratitis, and rarely, posttraumatic endophthalmitis or subcutaneous infection. Rare cases of endocarditis associated with valvuloplasty or prosthetic valves have been described. Invasive and disseminated infections, particularly with S. brevicaulis, may occur in immunosuppressed patients, manifesting as pneumonia or disseminated infection with skin lesions and fungemia. Patients at risk include those with acute leukemia and HSCT (48). Prognosis is related to immune reconstitution and the ability to perform surgical débridement on localized infections. Beauveria are ubiquitous fungi commonly found in soil. Because of their pathogenicity to many insect species, the organisms are incorporated into pesticides worldwide. Rarely, Beauveria may cause infections in humans, including keratitis and subcutaneous mycosis. Disseminated infections have occurred in patients with leukemia and HSCT (49). The organism appears to be susceptible to itraconazole and amphotericin B. 10. Hyalohyphomycosis—Infection Due to Hyaline Moulds 211 REFERENCES 1. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002;34: 909–917. 2. Nelson PE, Dignani MC, Anaissie EJ. Taxonomy, biology, and clinical aspects of Fusarium species. Clin Microbiol Rev 1994;7:479–504. 3. Hayden RT, Isotalo PA, Parrett T, et al. In situ hybridization for the differentiation of Aspergillus, Fusarium, and Pseudallescheria species in tissue section. Diagn Mol Pathol 2003;12:21–26. 4. Elvers KT, Leeming K, Moore CP, Lappin-Scott HM. Bacterial-fungal biofilms in flowing water photo-processing tanks. J Appl Microbiol 1998;84:607–618. 5. Doczi I, Gyetvai T, Kredics L, Nagy E. Involvement of Fusarium spp. in fungal keratitis. Clin Microbiol Infect 2004;10:773–776. 6. Fusarium keratitis–multiple states, 2006. MMWR Morb Mortal Wkly Rep 2006;55: 400–401. 7. Gabriele P, Hutchins RK. Fusarium endophthalmitis in an intravenous drug abuser. Am J Ophthalmol 1996;122:119–121. 8. Flynn JT, Meislich D, Kaiser BA, Polinsky MS, Baluarte HJ. Fusarium peritonitis in a child on peritoneal dialysis: case report and review of the literature. Perit Dial Int 1996;16:52–57. 9. Velasco E, Martins CA, Nucci M. Successful treatment of catheter-related fusarial infection in immunocompromised children. Eur J Clin Microbiol Infect Dis 1995;14:697–699. 10. Murray CK, Beckius ML, McAllister K. Fusarium proliferatum superficial suppurative thrombophlebitis. Mil Med 2003;168:426–427. 11. Kurien M, Anandi V, Raman R, Brahmadathan KN. Maxillary sinus fusariosis in immuno- competent hosts. J Laryngol Otol 1992;106:733–736. 12. Madhavan M, Ratnakar C, Veliath AJ, Kanungo R, Smile SR, Bhat S. Primary disseminated fusarial infection. Postgrad Med J 1992;68:143–144. 13. Nucci M, Anaissie E. Cutaneous infection by Fusarium species in healthy and immuno- compromised hosts: implications for diagnosis and management. Clin Infect Dis 2002;35: 909–920. 14. Jakle C, Leek JC, Olson DA, Robbins DL. Septic arthritis due to Fusarium solani. J Rheumatol 1983;10:151–153. 15. Sierra-Hoffman M, Paltiyevich-Gibson S, Carpenter JL, Hurley DL. Fusarium osteomyelitis: case report and review of the literature. Scand J Infect Dis 2005;37:237–240. 16. Boutati EI, Anaissie EJ. Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years’ experience at a cancer center and implications for management. Blood 1997;90:999–1008. 17. Nucci M, Marr KA, Queiroz-Telles F, et al. Fusarium infection in hematopoietic stem cell transplant recipients. Clin Infect Dis 2004;38:1237–1242. 18. Nucci M, Anaissie EJ, Queiroz-Telles F, et al. Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection. Cancer 2003;98:315–319. 19. Sampathkumar P, Paya CV. Fusarium infection after solid-organ transplantation. Clin Infect Dis 2001;32:1237–1240. 20. Anaissie EJ, Kuchar RT, Rex JH, et al. Fusariosis associated with pathogenic Fusarium species colonization of a hospital water system: a new paradigm for the epidemiology of opportunistic mould infections. Clin Infect Dis 2001;33:1871–1878. 21. Anaissie EJ, Stratton SL, Dignani MC, et al. Cleaning patient shower facilities: a novel approach to reducing patient exposure to aerosolized Aspergillus species and other oppor- tunistic moulds. Clin Infect Dis 2002;35:E86–E88. 212 Rhonda V. Fleming and Elias J. Anaissie 22. Girmenia C, Arcese W, Micozzi A, Martino P, Bianco P, Morace G. Onychomycosis as a possible origin of disseminated Fusarium solani infection in a patient with severe aplastic anemia. Clin Infect Dis 1992;14:1167. 23. Schell WA. New aspects of emerging fungal pathogens. A multifaceted challenge. Clin Lab Med 1995;15:365–387. 24. Hue FX, Huerre M, Rouffault MA, de Bievre C. Specific detection of Fusarium species in blood and tissues by a PCR technique. J Clin Microbiol 1999;37:2434–2438. 25. Ostrosky-Zeichner L, Alexander BD, Kett DH, et al. Multicenter clinical evaluation of the (1–>3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 2005;41:654–659. 26. Cuenca-Estrella M, Gomez-Lopez A, Mellado E, Garcia-Effron G, Monzon A, Rodriguez- Tudela JL. In vitro activity of ravuconazole against 923 clinical isolates of nondermatophyte filamentous fungi. Antimicrob Agents Chemother 2005;49:5136–5138. 27. Idigoras P, Perez-Trallero E, Pineiro L, et al. Disseminated infection and colonization by Scedosporium prolificans: a review of 18 cases, 1990–1999. Clin Infect Dis 2001;32: E158–E165. 28. Rainer J, De Hoog GS. Molecular taxonomy and ecology of Pseudallescheria, Petriella and Scedosporium prolificans (Microascaceae) containing opportunistic agents on humans. Mycol Res 2006;110:151–160. 29. Castiglioni B, Sutton DA, Rinaldi MG, Fung J, Kusne S. Pseudallescheria boydii (anamorph Scedosporium apiospermum). Infection in solid organ transplant recipients in a tertiary medical center and review of the literature. Medicine (Baltimore) 2002;81:333–348. 30. Montero A, Cohen JE, Fernandez MA, Mazzolini G, Gomez CR, Perugini J. Cerebral pseudallescheriasis due to Pseudallescheria boydii as the first manifestation of AIDS. Clin Infect Dis 1998;26:1476–1477. 31. Carrillo AJ, Guarro J. In vitro activities of four novel triazoles against Scedosporium spp. Antimicrob Agents Chemother 2001;45:2151–2153. 32. Radford SA, Johnson EM, Warnock DW. In vitro studies of activity of voriconazole (UK-109,496), a new triazole antifungal agent, against emerging and less-common mould pathogens. Antimicrob Agents Chemother 1997;41:841–843. 33. Walsh TJ, Peter J, McGough DA, Fothergill AW, Rinaldi MG, Pizzo PA. Activities of amphotericin B and antifungal azoles alone and in combination against Pseudallescheria boydii. Antimicrob Agents Chemother 1995;39:1361–1364. 34. Gosbell IB, Toumasatos V, Yong J, Kuo RS, Ellis DH, Perrie RC. Cure of orthopaedic infection with Scedosporium prolificans, using voriconazole plus terbinafine, without the need for radical surgery. Mycoses 2003;46:233–236. 35. Fleming RV, Walsh TJ, Anaissie EJ. Emerging and less common fungal pathogens. Infect Dis Clin North Am 2002;16:915–933. 36. Espinel-Ingroff A. Comparison of In vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts. J Clin Microbiol 1998;36:2950–2956. 37. Guarro J, Gams W, Pujol I, Gene J. Acremonium species: new emerging fungal opportunists – in vitro antifungal susceptibilities and review. Clin Infect Dis 1997;25:1222–1229. 38. Fincher RM, Fisher JF, Lovell RD, Newman CL, Espinel-Ingroff A, Shadomy HJ. Infection due to the fungus Acremonium (Cephalosporium). Medicine (Baltimore) 1991;70:398–409. 39. Liu K, Howell DN, Perfect JR, Schell WA. Morphologic criteria for the preliminary identification of Fusarium, Paecilomyces, and Acremonium species by histopathology. Am J Clin Pathol 1998;109:45–54. 40. Supparatpinyo K, Khamwan C, Baosoung V, Nelson KE, Sirisanthana T. Disseminated Penicillium marneffei infection in southeast Asia. Lancet 1994;344:110–113. 10. Hyalohyphomycosis—Infection Due to Hyaline Moulds 213 41. Sirisanthana T, Supparatpinyo K. Epidemiology and management of penicilliosis in human immunodeficiency virus-infected patients. Int J Infect Dis 1998;3:48–53. 42. Sun HY, Chen MY, Hsiao CF, Hsieh SM, Hung CC, Chang SC. Endemic fungal infections caused by Cryptococcus neoformans and Penicillium marneffei in patients infected with human immunodeficiency virus and treated with highly active anti-retroviral therapy. Clin Microbiol Infect 2006;12:381–388. 43. Supparatpinyo K, Chiewchanvit S, Hirunsri P, Uthammachai C, Nelson KE, Sirisanthana T. Penicillium marneffei infection in patients infected with human immunodeficiency virus. Clin Infect Dis 1992;14:871–874. 44. Duong TA. Infection due to Penicillium marneffei, an emerging pathogen: review of 155 reported cases. Clin Infect Dis 1996;23:125–130. 45. Sirisanthana T, Supparatpinyo K, Perriens J, Nelson KE. Amphotericin B and itraconazole for treatment of disseminated Penicillium marneffei infection in human immunodeficiency virus-infected patients. Clin Infect Dis 1998;26:1107–1110. 46. Supparatpinyo K, Perriens J, Nelson KE, Sirisanthana T. A controlled trial of itraconazole to prevent relapse of Penicillium marneffei infection in patients infected with the human immunodeficiency virus. N Engl J Med 1998;339:1739–1743. 47. Hung CC, Chen MY, Hsieh SM, Sheng WH, Hsiao CF, Chang SC. Discontinuation of secondary prophylaxis for penicilliosis marneffei in AIDS patients responding to highly active antiretroviral therapy. AIDS 2002;16:672–673. 48. Cuenca-Estrella M, Gomez-Lopez A, Mellado E, Buitrago MJ, Monzon A, Rodriguez- Tudela JL. Scopulariopsis brevicaulis, a fungal pathogen resistant to broad-spectrum antifungal agents. Antimicrob Agents Chemother 2003;47:2339–2341. 49. Tucker DL, Beresford CH, Sigler L, Rogers K. Disseminated Beauveria bassiana infection in a patient with acute lymphoblastic leukemia. J Clin Microbiol 2004;42:5412–5414. 50. Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J Clin Microbiol 2003;41:3623–3626. 51. Pfaller MA, Diekema DJ. Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. J Clin Microbiol 2004;42:4419–4431. 52. Sabatelli F, Patel R, Mann PA, et al. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important moulds and yeasts. Antimicrob Agents Chemother 2006;50:2009–2015. SUGGESTED READINGS Dignani MC, Anaissie E. Human fusariosis. Clin Microbiol Infect 2004;10(Suppl 1):67–75. Fincher RM, Fisher JF, Lovell RD, Newman CL, Espinel-Ingroff A, Shadomy HJ. Infection due to the fungus Acremonium (Cephalosporium). Medicine (Baltimore) 1991;70:398–409. Fleming RV, Walsh TJ, Anaissie EJ. Emerging and less common fungal pathogens. Infect Dis Clin North Am 2002;16:915–933. Husain S, Alexander BD, Munoz P, et al. Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi. Clin Infect Dis 2003;37:221–229. Panackal AA, Marr KA. Scedosporium/Pseudallescheria infections. Semin Respir Crit Care Med 2004;25:171–181. Schinabeck MK, Ghannoum MA. Human hyalohyphomycoses: a review of human infections due to Acremonium spp., Paecilomyces spp., Penicillium spp., and Scopulariopsis spp. J Chemother 2003;15 (Suppl 2):5–15. 11 Phaeohyphomycosis—Infection Due to Dark (Dematiaceous) Moulds Sanjay G. Revankar, MD 1. INTRODUCTION Dematiaceous, or darkly pigmented, fungi are a large heterogeneous group of organisms that have been associated with a wide variety of clinical syndromes. These are uncommon causes of human disease, but can be responsible for life-threatening infections in both immunocompromised and immunocompetent individuals. In recent years, these fungi have been increasingly recognized as important pathogens, and the spectrum of diseases they are associated with has also broadened. These fungi may cause hypersenstivity disorders and superficial infections, but typically the term phaeohyphomycosis is limited to deeper infections. Two other more classically described clinical syndromes caused by the dark-walled fungi, typically distinguished by characteristic histologic findings, are chromoblastomycosis and mycetoma. Chromoblastomycosis and mycetoma are caused by a small group of fungi that are associated with characteristic structures in tissue and are usually seen in tropical areas (1). These are discussed in the chapter on subcutaneous mycoses (Chapter 21). Phaeohyphomycosis is a term introduced by

Ajello et al. in 1974 that literally means “infection caused by dark walled fungi” (2). It is a catch-all term generally reserved for the remainder of clinical syndromes caused by dematiaceous fungi that range from superficial infections and allergic disease to brain abscess and widely disseminated disease (3). These fungi are alternately called phaeoid, dematia- ceous, dark, or black moulds. While typically phaeohyphomycosis is a term limited to infections caused by the dark moulds, there are dark yeasts that rarely cause infection, and these are also included under this grouping by many experts. 2. ETIOLOGIC AGENTS More than 100 species and 60 genera of dematiaceous fungi have been implicated in human disease (4). The common characteristic among these fungi is the presence of melanin in their cell walls, which imparts the dark color to their conidia or spores and From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 215 216 Sanjay G. Revankar Table 11.1 Clinical spectrum and treatment of phaeohyphomycosis Clinical syndrome Commonly associated fungi Therapy Allergic fungal Curvularia, Bipolaris Corticosteroids ± itraconazole sinusitis/Allergic or voriconazole bronchopulmonary mycosis (disease) Onychomycosis Onychocola, Alternaria Itraconazole or terbinafine Keratitis Curvularia, Bipolaris, Topical natamycin ± itraconazole or Exserohilum, Lasiodiplodia voriconazole Subcutaneous Exophiala, Alternaria, Surgery ± itraconazole or voriconazole infection Phialophora Pneumonia Ochroconis, Exophiala, Itraconazole or voriconazole, Chaetomium (amphotericin B if severe) Brain abscess Cladophialophora (C. See text bantiana), Ramichloridium (R. mackenzei), Ochroconis Disseminated Scedosporium (S. prolificans), See text disease Bipolaris, Wangiella hyphae. Their colonies are typically brown to black in color as well. As the number of patients immunocompromised from diseases and medical therapy increases, additional species are being reported as causes of human disease, expanding an already long list of potential pathogens. Common genera associated with specific clinical syndromes are listed in Table 11.1. Guidelines are available regarding the handling of potentially infectious fungi in the laboratory setting. It is suggested that work with cultures of certain well-known pathogenic fungi, such as Coccidioides immitis and Histoplasma capsulatum, be conducted in a Biosafety Level 3 facility, which requires a separate negative pressure room. Recently, certain agents of phaeohyphomycosis, in particular Cladophialophora bantiana, have been included in the list of fungi that should be kept under Biosafety Level 2 containment (5). This seems reasonable given their propensity, albeit rarely, for causing life-threatening infection in normal individuals. 3. EPIDEMIOLOGY These fungi are typically soil organisms and generally distributed worldwide (6). However, there are species that do appear to be geographically restricted, such as Ramichloridium mackenzei, which has only been seen in patients from the Middle East (7). Exposure is thought to be from inhalation or minor trauma, which may not even be noticed by the patient. Surveys of outdoor air for fungal spores routinely observe dematiaceous fungi (8). This suggests that most if not all individuals are exposed to them, though they remain uncommon causes of disease. These fungi may also be found to be contaminants in cultures, making the determination of clinical significance problematic. A high degree of clinical suspicion as well as correlation with appropriate clinical findings and histopathology is required when interpreting culture results. 11. Phaeohyphomycosis—Infection Due to Dark Moulds 217 4. PATHOGENESIS AND IMMUNOLOGY Little is known regarding the pathogenic mechanisms by which these fungi cause disease. One of the likely virulence factors is the presence of melanin in the cell wall, which is common to all dematiaceous fungi. It may confer a protective advantage by scavenging free radicals that are produced by phagocytic cells in their oxidative burst that normally kill most organisms (9). In addition, melanin may bind to hydrolytic enzymes, thereby preventing their action on the plasma membrane (9). In the yeasts C. neoformans and W. dermatitidis, disruption of melanin production leads to markedly reduced virulence in animal models (10,11). Melanin has also been associated with decreased susceptibility of fungi to certain antifungals, possibly by binding these drugs (12,13). It is interesting to note that almost all allergic disease and eosinophilia is caused by two genera, Bipolaris and Curvularia , though the virulence factors responsible for eliciting allergic reactions are unclear at present (14). 5. CLINICAL MANIFESTATIONS 5.1. Allergic Disease Relatively few species have been associated with allergic disease. Alternaria alternata is thought to be involved in some cases of asthma (15). Whether dematia- ceous fungi may be responsible for symptoms of allergic rhinitis is unclear, as it is difficult to quantitate exposure and to distinguish them from other causes (16). Bipolaris and Curvularia are responsible for most cases of allergic fungal sinusitis (AFS) and allergic bronchopulmonary mycosis (ABPM). Patients with AFS usually present with chronic sinus symptoms that are not responsive to antibiotics. Previ- ously, Aspergillus was thought to be the most common fungus responsible for allergic sinusitis, but it is now appreciated that disease due to dematiaceous fungi actually comprises the majority of cases (17). Criteria have been suggested for this disease, and include (1) nasal polyps; (2) presence of allergic mucin, containing Charcot-Leyden crystals and eosinophils; (3) hyphal elements in the mucosa without evidence of tissue invasion; (4) positive skin test to fungal allergens; and (5) on computed tomography (CT) scans, characteristic areas of central hyperattenuation within the sinus cavity (18). Diagnosis generally depends on demonstration of allergic mucin, with or without actual culture of the organism. Allergic bronchopulmonary mycosis (ABPM) (or disease [ABPD]) is similar in presentation to allergic bronchopulmonary aspergillosis (ABPA), which is typically seen in patients with asthma or cystic fibrosis (19). Criteria for the diagnosis of ABPA in patients with asthma include (1) asthma, (2) positive skin test for fungal allergens, (3) elevated IgE levels, (4) Aspergillus-specific IgE, and (5) proximal bronchiec- tasis (19). Similar criteria for ABPM are not established, but finding allergic mucin (Charcot-Leyden crystals and eosinophils) without tissue invasion, as in AFS, makes this diagnosis highly likely (20). 218 Sanjay G. Revankar 5.2. Focal Infection 5.2.1. Superficial Infection Superficial infections are the most common form of disease associated with phaeo- hyphomycosis. These include black piedra, tinea nigra, and onychomycosis. Black piedra is a nodular disease of the scalp hair, typically seen in tropical climates, predominantly in South America. Caused by Piedraia hortae, this is chiefly a disease of only cosmetic impact to the sufferer. Tinea nigra is primarily seen in tropical areas, and involves only the stratum corneum of the skin. Patients are generally asymptomatic, presenting with brownish- black macular lesions, almost exclusively on the palms and soles. Hortaea werneckii is the most commonly isolated species, though Stenella araguata has also been cultured from lesions (21). Tinea nigra may be confused with a variety of other diseases, including dysplastic nevi, melanoma, syphilis, or Addison’s disease. Diagnosis is made by scrapings of lesions and culture. As it is a very superficial infection, simple scraping or abrasion can be curative, though topical treatments such as keratolytics or imidazole creams are also highly effective (21). Dematiaceous fungi are rare causes of onychomycosis. Clinical features may include a history of trauma, involvement of only one or two toenails, and lack of response to standard systemic therapy (22). Onychocola and Alternaria have been reported, with the former being highly resistant to therapy. 5.2.2. Keratitis Fungal keratitis is an important ophthalmologic problem, particularly in tropical areas of the world. In one large series, 40% of all infectious keratitis was caused by fungi, almost exclusively moulds (23). The most common fungi are Fusarium and Aspergillus, followed by dematiaceous fungi (up to 8% to 17% of cases) (24). Approximately half the cases are associated with trauma; prior eye surgery, diabetes, and use of contact lens use have also been noted as important risk factors (24). In a study from the United States of 43 cases of Curvularia keratitis, almost all were associated with trauma (25). Plants were the most common source, though several cases involving metal injuries were seen as well. 5.2.3. Subcutaneous Infection There are numerous case reports of subcutaneous infection due to a wide variety of species (26,27). Minor trauma is the usual inciting factor, though it may be unrec- ognized by the patient. Lesions typically occur on exposed areas of the body and often appear cystic or papular. Immunocompromised patients are at increased risk of subsequent dissemination. Occasionally, these infections may involve joints or bone. 5.2.4. Pneumonia Nonallergic pulmonary disease is usually seen in immunocompromised patients, and may be due to a wide variety of species, in contrast to allergic disease (14,28–31). Clinical manifestations include pneumonia, asymptomatic solitary pulmonary nodules, and endobronchial lesions which may cause hemoptysis. 11. Phaeohyphomycosis—Infection Due to Dark Moulds 219 5.2.5. Brain Abscess This is a rare but frequently fatal manifestation of phaeohyphomycosis (32). Inter- estingly, more than half of reported cases have occurred in patients with no risk factors or known immunodeficiency. Lesions are usually solitary. Symptoms may include headache, neurologic deficits, and seizures, though the classic triad seen in bacterial brain abscess (fever, headache, and focal neurologic deficit) was not usually present. The most commonly isolated organism is Cladophialophora bantiana, particularly in immunocompetent patients. The pathogenesis may be hematogenous spread from an initial, presumably subclinical pulmonary focus. It remains unclear why these fungi preferentially cause CNS disease. 5.3. Disseminated Infection This is the most uncommon manifestation of infection seen with dematiaceous fungi. Most patients are immunocompromised, though occasional patients without known immunodeficiency or risk factors have developed disseminated disease as well (33). In contrast to most invasive mould infections, blood cultures are often positive. The most commonly isolated fungus, S. prolificans, may also be associated with septic shock. Peripheral eosinophilia, seen in 11% of these cases, was generally associated with Bipolaris or Curvularia. 6. DIAGNOSIS In contrast to other common mycoses that cause human disease, there are no serologic or antigen tests available to detect these fungi in blood or tissue. The diagnosis of phaeohyphomycosis currently rests on pathologic examination of clinical specimens and careful gross and microscopic examination of cultures (Fig. 11.1). Hospital labora- tories can generally identify the most common genera associated with human disease Clinical Suspicion Obtain clinical material (tissue, blood, aspirate, etc.) Microscopic examination Culture Macroscopic - observe for darkly pigmented colonies Microscopic - identify by morphology (hyphae, yeasts, conidia) Direct observation Histopathology Observe for fungal elements Observe for irregular hyphae with dark cell walls and beaded yeast-like forms; positive staining by Fontana- Masson method Fig. 11.1. Diagnostic approach to phaeohyphomycosis. 220 Sanjay G. Revankar Fig. 11.2. Commonly seen fungi causing phaeohyphomycosis. Left: Curvularia lunata. Right: Cladophialophora bantiana. [Figure in color on CD-ROM]. Fig. 11.3. Fontana-Masson stain of Bipolaris infection in the lung, demonstrating irregular hyphae and beaded yeast-like forms. [Figure in color on CD-ROM]. 11. Phaeohyphomycosis—Infection Due to Dark Moulds 221 (Fig. 11.2) (see also Fig. 2.13, Chapter 2), though referral to a reference laboratory is often needed to identify unusual species. As many of these are rarely seen in practice, a high degree of clinical suspicion is required when interpreting culture results. In tissue, these fungi will stain strongly with the Fontana-Masson stain, which is specific for melanin (Fig. 11.3) (3). This can be helpful in distinguishing these fungi from other species, particularly Aspergillus. In addition, hyphae typically appear more fragmented in tissue than seen with Aspergillus, with irregular septate hyphae and beaded, yeast-like forms (3). 7. TREATMENT Therapy is not standardized for any of these clinical syndromes, and randomized trials are unlikely given the sporadic nature of cases. Itraconazole and voriconazole demonstrate the most consistent in vitro activity against this group of fungi, though far more clinical experience has accumulated with itraconazole (34). Amphotericin B may be used for severe infections in unstable patients; high doses of lipid formulations may have a role in the treatment of refractory cases or in patients intolerant of standard amphotericin B. However, some species of dematiaceous fungi are resistant to this agent. Once the infection is under control, longer term therapy with a broad-spectrum oral azole is often reasonable until a complete response is achieved, which may require several weeks to months. Other agents have limited roles in treating these fungi. Ketoconazole is not well tolerated, and fluconazole has poor activity against these fungi in general. Terbinafine and flucytosine have occasionally been used for subcutaneous infections in patients refractory to other therapy. Echinocandins do not appear to be very useful as single agents. Combination therapy is a

potentially useful therapeutic strategy for refractory infections, particularly brain abscess and disseminated disease, though it has not been well studied. Suggested therapies for specific infections are summarized in Table 11.1. 7.1. Allergic Disease Steroids are the mainstay of treatment for allergic disease caused by these fungi, especially in asthma, though other modalities may have a role in specific clinical situations. For example, therapy for AFS consists of systemic corticosteroids and surgery to remove the mucin, which is often tenacious. Antifungal therapy, usually in the form of itraconazole, may play a role in reducing the requirement for corticosteroids, but this is not routinely recommended (35). Other azoles have only rarely been used in the treatment of this disease. Allergic bronchopulmonary mycosis (ABPM) can be treated with systemic corticos- teroids as in ABPA; prednisone at a dose of 0.5 mg/kg per day for 2 weeks, followed by a slow taper over 2 to 3 months or longer (19). Itraconazole has been used as a steroid sparing agent in APBA, but its efficacy is not clear, and routine use of itraconazole is not generally recommended (19). 222 Sanjay G. Revankar 7.2. Focal Infection 7.2.1. Superficial Infection Itraconazole and terbinafine are the most commonly used systemic agents for onychomycosis, and may be combined with topical therapy for refractory cases (36). There is no published experience with voriconazole. 7.2.2. Keratitis For keratitis, topical 5% natamycin is used almost exclusively, with only a few severe cases requiring adjunctive therapy, usually with an azole (23,37). Itraconazole has the best in vitro activity. The majority of isolates are resistant to flucytosine. Surgery, including penetrating keratoplasty, is often needed. Enucleation is occasionally required due to poor clinical response. Many patients do not recover complete visual acuity despite aggressive therapy. 7.2.3. Subcutaneous Infection Subcutaneous lesions will often respond to surgical excision alone (38). Oral systemic therapy with a broad-spectrum azole antifungal agent in conjunction with surgery is frequently employed and has been used successfully, particularly in immuno- compromised patients (39,40). 7.2.4. Pneumonia Therapy consists of systemic antifungal agents, usually amphotericin B or itraconazole initially, followed by itraconazole for a more prolonged period (14). Mortality rates are high in immunocompromised patients. Experience with voriconazole is currently only anecdotal (41). 7.2.5. Brain Abscess Therapy published in the literature has varied greatly depending on the case report, and there is no standard treatment. A retrospective analysis of 101 reported cases suggested that the combination of amphotericin B (high-dose lipid formulation), flucy- tosine, and itraconazole may be associated with improved survival, though it was not frequently used (32). Voriconazole may also prove useful. High doses of azoles have been suggested as an option, though there are no studies confirming this approach. Complete excision of brain abscesses may lead to better outcomes than aspiration or partial excision. Overall mortality is greater than 70%. 7.3. Disseminated Infection A recent literature review suggested the mortality rate is greater than 70%, despite aggressive antifungal therapy (33). There were no antifungal regimens associated with improved survival in disseminated infection. High-dose lipid amphotericin B may be reasonable for initial therapy, given its fungicidal activity for many fungi. Addition of a broad-spectrum azole or echinocandin could be considered in individuals failing therapy. Infection with S. prolificans has been associated with a nearly 100% mortality in the absence of recovery from neutropenia, as it is generally resistant to all available antifungal agents. Recent reports have suggested that the combination of itraconazole or voriconazole with terbinafine may be synergistic against this species, though the clinical relevance of this finding is unclear (42,43). 11. Phaeohyphomycosis—Infection Due to Dark Moulds 223 REFERENCES 1. McGinnis MR. Chromoblastomycosis and phaeohyphomycosis: new concepts, diagnosis, and mycology. J Am Acad Dermatol 1983;8:1–16. 2. Ajello L, Georg LK, Steigbigel RT, Wang CJ. A case of phaeohyphomycosis caused by a new species of Phialophora. Mycologia 1974;66:490–498. 3. Rinaldi MG. Phaeohyphomycosis. Dermatol Clin 1996;14:147–153. 4. Matsumoto T, Ajello L, Matsuda T, Szaniszlo PJ, Walsh TJ. Developments in hyalohy- phomycosis and phaeohyphomycosis. J Med Vet Mycol 1994;32(Suppl 1):329–349. 5. 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Allergic fungal rhinosinusitis: pathophysiology, epidemiology, and diagnosis. Otolaryngol Clin North Am 2000;33:399–409. 19. Greenberger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 2002;110:685–692. 20. Hamilton BG, Humphreys CW, Conner WC, Hospenthal DR. Allergic bronchopulmonary disease secondary to Bipolaris spicifera: Case report. J Bronchol 2006;13:77–79. 21. Perez C, Colella MT, Olaizola C, de Capriles CH, Magaldi S, Mata-Essayag S. Tinea nigra: report of twelve cases in Venezuela. Mycopathologia 2005;160:235–238. 22. Gupta AK, Ryder JE, Baran R, Summerbell RC. Non-dermatophyte onychomycosis. Dermatol Clin 2003;21:257–268. 23. Gopinathan U, Garg P, Fernandes M, Sharma S, Athmanathan S, Rao GN. The epidemi- ological features and laboratory results of fungal keratitis: a 10-year review at a referral eye care center in South India. Cornea 2002;21:555–559. 24. Srinivasan M. Fungal keratitis. Curr Opin Ophthalmol 2004;15:321–327. 224 Sanjay G. Revankar 25. Wilhelmus KR, Jones DB. Curvularia keratitis. Trans Am Ophthalmol Soc 2001;99:111–130. 26. Sutton DA, Rinaldi MG, Kielhofner M. First US report of subcutaneous phaeohyphomy- cosis caused by Veronaea botryosa in a heart transplant recipient and review of the literature. J Clin Microbiol 2004;42:2843–2846. 27. Chuan MT, Wu MC. Subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei: successful treatment with itraconazole. Int J Dermatol 1995;34:563–566. 28. Odell JA, Alvarez S, Cvitkovich DG, Cortese DA, McComb BL. Multiple lung abscesses due to Ochroconis gallopavum, a dematiaceous fungus, in a nonimmunocompromised wood pulp worker. Chest 2000;118:1503–1505. 29. Yeghen T, Fenelon L, Campbell CK, et al. Chaetomium pneumonia in patient with acute myeloid leukaemia. J Clin Pathol 1996;49:184–186. 30. Mazur JE, Judson MA. A case report of a Dactylaria fungal infection in a lung transplant patient. Chest 2001;119:651–653. 31. Manian FA, Brischetto MJ. 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Summerbell RC, Krajden S, Levine R, Fuksa M. Subcutaneous phaeohyphomycosis caused by Lasiodiplodia theobromae and successfully treated surgically. Med Mycol 2004;42: 543–547. 39. Kimura M, Goto A, Furuta T, Satou T, Hashimoto S, Nishimura K. Multifocal subcutaneous phaeohyphomycosis caused by Phialophora verrucosa. Arch Pathol Lab Med 2003;127: 91–93. 40. Clancy CJ, Wingard JR, Hong NM. Subcutaneous phaeohyphomycosis in transplant recip- ients: review of the literature and demonstration of in vitro synergy between antifungal agents. Med Mycol 2000;38:169–175. 41. Diemert D, Kunimoto D, Sand C, Rennie R. Sputum isolation of Wangiella dermatitidis in patients with cystic fibrosis. Scand J Infect Dis 2001;33:777–779. 42. Meletiadis J, Mouton JW, Meis JF, Verweij PE. Combination chemotherapy for the treatment of invasive infections by Scedosporium prolificans. Clin Microbiol Infect 2000;6:336–337. 43. Howden BP, Slavin MA, Schwarer AP, Mijch AM. Successful control of disseminated Scedosporium prolificans infection with a combination of voriconazole and terbinafine. Eur J Clin Microbiol Infect Dis 2003;22:111–113. SUGGESTED READINGS Clancy CJ, Wingard JR, Hong NM. Subcutaneous phaeohyphomycosis in transplant recipients: review of the literature and demonstration of in vitro synergy between antifungal agents. Med Mycol 2000;38:169–175. 11. Phaeohyphomycosis—Infection Due to Dark Moulds 225 Jacobson ES. Pathogenic roles for fungal melanins. Clin Microbiol Rev 2000;13:708–717. Kuhn FA, Javer AR. Allergic fungal rhinosinusitis: perioperative management, prevention of recurrence, and role of steroids and antifungal agents. Otolaryngol Clin North Am 2000;33:419–433. Revankar SG, Patterson JE, Sutton DA, Pullen R, Rinaldi MG. Disseminated phaeohyphomy- cosis: review of an emerging mycosis. Clin Infect Dis 2002;34:467–476. Revankar SG, Sutton DA, Rinaldi MG. Primary central nervous system phaeohyphomycosis: a review of 101 cases. Clin Infect Dis 2004;38:206–216. Sharkey PK, Graybill JR, Rinaldi MG, et al. Itraconazole treatment of phaeohyphomycosis. J Am Acad Dermatol 1990;23:577–586. Srinivasan M. Fungal keratitis. Curr Opin Ophthalmol 2004;15:321–327. 12 Zygomycosis (Mucormycosis) Charalampos Antachopoulos, MD, Juan C. Gea-Banacloche, MD, and Thomas J. Walsh, MD 1. INTRODUCTION The class Zygomycetes includes a variety of filamentous fungi that may cause life- threatening human disease and, over the past decade, have emerged as an increasingly important cause of morbidity and mortality among immunocompromised patients (1,2). The first case of zygomycosis in humans was reported in 1885 by Platauf as Mycosis Mucorina. In many of the cases reported thereafter the infection was identified as “mucormycosis” or Mucor infection based solely on histological findings of wide, rarely septate hyphae, without culture confirmation. The use of the term “mucormy- cosis” was further promoted by the original classification of most of the pathogenic zygomycetes species as members of the genus Mucor. Many of these species were later reassigned into different genera or families (3). Consequently the term “zygomycosis” should be preferred, instead of “mucormycosis,” for infections caused by any of the zygomycetes species. Some authors still employ the term “mucormycosis,” however, for infections caused by members of the order Mucorales (3,4). Those who prefer the use of “mucormycosis” stress that the opportunistic disease due to those fungi in the order Mucorales differs substantially from disease caused by the other pathogenic zygomycetes order, Entomophthorales. 2. ETIOLOGIC AGENTS The medically important Zygomycetes encompass two orders of filamentous fungi with distinct morphologic, epidemiologic, and pathogenic characteristics, the Mucorales and the Entomophthorales (3,5–8) (Table 12.1). The majority of cases of zygomycosis in humans are caused by members of the order Mucorales. Organisms of the genus Rhizopus are by far the most common clinical isolates, with R. oryzae being the most frequently recovered species. Members of the genus Mucor are second to Rhizopus in order of frequency, while Cunninghamella, Apophysomyces, Absidia, Saksenaea, Rhizomucor and other genera each represent a significantly smaller percentage of clinical isolates (1,3,4). From: Infectious Disease: Diagnosis and Treatment of Human Mycoses Edited by: D. R. Hospenthal and M. G. Rinaldi © Humana Press Inc., Totowa, NJ 227 228 Charalampos Antachopoulos, Juan C. Gea-Banacloche, and Thomas J. Walsh Table 12.1 Taxonomic classification of the Zygomycetes Class Order Family Genus Species causing human disease Zygomycetes Mucorales Mucoraceae Absidia A. corymbifera Apophysomyces A. elegans Mucor M. circinelloides, M. ramosissimus, M. racemosus, M. hiemalis, M. rouxianus Rhizomucor R. pusillus Rhizopus R. oryzae (R. arrhizus), R. microsporus var. rhizopodiformis Cunninghamellaceae Cunninghamella C. bertholletiae Mortierellaceae Mortierella (animal pathogens) Saksenaceae Saksenaea S. vasiformis Syncephalastraceae Syncephalastrum S. racemosum Thamnidaceae Cokeromyces C. recurvatus Entomophthoralesa Ancylistaceae Conidiobolus* C. coronatus, C. incongruus Basidiobolaceae Basidiobolus* B. ranarum aIt has