to severe renal impairment Route, reduce dose, and Reasonable oral absorption (oral preparation) enterococcal strains usually respond to

Transcription

1 Drug class Aminopenicillin Aminopenicillin Aminopenicillin/βlactam inhibitor combination Drug Ampicillin Amoxicillin Amoxicillin/ clavulanate TABLE J.1 Aminopenicillins LWBK1580-App-J_p indd 1852 PO: 500/125 mg q8 h or 875/125 mg q12 h for severe infections or respiratory tract infections IV: 500 mg 1 g tds (higher doses: 2 g 4 hourly in endocarditis PO: 1 g q8 h IV: 2.0 g IV q4 h PO: 500 mg q6 h Usual dose in adults Bactericide Some gramnegative activity Allopurinol (increased frequency of rash) Warfarin (increased INR) Primary mode of elimination: Renal Reasonable oral absorption (oral preparation) Reduce dose in moderate to severe renal impairment Primary mode of elimination: Renal Reduce dose in moderate to severe renal impairment 875/125 mg formulation should not be used in patients with CrCl <30 ml/min Aerobic gram-positive micro-organisms Streptococcus pneumoniae (including isolates with penicillin MICs 2 μg/ml) Aerobic gram-negative micro-organisms Haemophilus influenzae (including β-lactamase producing isolates) Moraxella catarrhalis (including β-lactamase producing isolates) The following in vitro data are available, but their clinical significance is unknown. Aerobic gram-positive micro-organisms Staphylococcus aureus (including β-lactamase producing isolates) NOTE: Staphylococci that are resistant to methicillin/oxacillin must be considered resistant to amoxicillin/clavulanic acid S. pyogenes Primary mode of elimination: Renal Reduce dose in moderate to severe renal impairment Streptococcus pneumoniae Haemophilus influenzae (except COPD patients) β-hemolytic Streptococci Streptococcus pyogenes do not produce β-lactamase Enterococcus faecalis Streptococcus pneumoniae; Staphylococcus aureus (penicillinase and nonpenicillinase producing); Haemophilus influenzae, and group A β-hemolytic Streptococci Bacterial meningitis caused by Escherichia coli, group B Streptococci, and other gram-negative bacteria (Listeria monocytogenes, Neisseria meningitidis) Endocarditis caused by susceptible grampositive organisms including Streptococcus sp., penicillin G susceptible Staphylococci, and Enterococci. Endocarditis due to enterococcal strains usually respond to intravenous therapy Gram-negative sepsis caused by E. coli, Proteus mirabilis, and Salmonella sp. Gastrointestinal infections caused by Salmonella typhosa (typhoid fever), other Salmonella sp., and Shigella sp. Urinary tract infections caused by E. coli and Proteus mirabilis Spectrum of activity, indications, and active against most strains of Appendix J Antibiotics 1852

2 TABLE J.1 Aminopenicillins (Continued) Drug Drug class Usual dose in adults Spectrum of activity, indications, and active against most strains of Ampicillin/ sulbactam Aminopenicillin/βlactam inhibitor combination IV: g q6 h Remember: Na + content = 4.2 meq/g Total dose of sulbactam should not exceed 4 g/d Bactericide Broad-spectrum antibiotic and a β-lactamase inhibitor For mild or moderate infection, 1.5 g IV q6 h Pseudoresistance with E. coli/klebsiella (in vitro) Gram-negative bacteria Haemophilus influenzae (β-lactamase and non β-lactamase producing); Moraxella (Branhamella) catarrhalis (β-lactamase and non β-lactamase producing); Escherichia coli (β-lactamase and non βlactamase producing); Klebsiella spp. (all known strains are β-lactamase producing); Proteus mirabilis (β-lactamase and non β-lactamase producing); Proteus vulgaris; Providencia rettgeri; Providencia stuartii; Morganella morganii; Neisseria gonorrhoeae (β-lactamase and non βlactamase producing). Anaerobes Clostridium sp.; Peptococcus sp.; Peptostreptococcus sp.; Bacteroides sp., including B. fragilis INR, international normalized ratio; COPD, chronic obstructive pulmonary disease; MIC, minimum inhibitory concentration; CrCl, creatinine clearance. Primary mode of elimination: Renal and hepatic Ampicillin and sulbactam for injection may be administered by either the IV or the IM routes In patients with impairment of renal function, the elimination kinetics of ampicillin and sulbactam are similarly affected 1853 LWBK1580-App-J_p indd 1853

3 TABLE J.2 Antipseudomonal Penicillins Spectrum of activity, indications, and active against most strains of Piperacillin Antipseudomonal penicillin Piperacillin/ tazobactam Antipseudomonal penicillin IV: 34 g q48 h Drug interaction with aminoglycosides in renal failure IV: 4.5 g q8 h Pneumonia nosocomial, use 4.5 g (IV) q6 h Drug interaction with aminoglycosides and vecuronium Prophylaxis: Piperacillin is indicated for prophylactic use in surgery including intra-abdominal (gastrointestinal and biliary) procedures, vaginal hysterectomy, abdominal hysterectomy, and cesarean section. Piperacillin should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. Indications and use Intra-abdominal infections including hepatobiliary and surgical infections caused by E. coli, Pseudomonas aeruginosa, Enterococci, Clostridium spp., anaerobic cocci, or Bacteroides spp., including B. fragilis. Urinary tract infections caused by E. coli, Klebsiella spp., P. aeruginosa, Proteus spp. including P. mirabilis, or Enterococci Gynecologic infections including endometritis, pelvic inflammatory disease, pelvic cellulitis caused by Bacteroides spp. including B. fragilis, anaerobic cocci, Neisseria gonorrhoeae, or Enterococci (E. faecalis) Septicemia including bacteremia caused by E. coli, Klebsiella spp., Enterobacter spp., Serratia spp., P. mirabilis, S. pneumoniae, Enterococci, P. aeruginosa, Bacteroides spp., or anaerobic cocci. Lower respiratory tract infections caused by E. coli, Klebsiella spp., Enterobacter spp., P. aeruginosa, Serratia spp., H. influenzae, Bacteroides spp., or anaerobic cocci. Skin and skin structure infections caused by E. coli, Klebsiella spp., Serratia spp., Acinetobacter spp., Enterobacter spp., P. aeruginosa, Morganella morganii, Providencia rettgeri, Proteus vulgaris, P. mirabilis, Bacteroides spp. including B. fragilis, anaerobic cocci, or Enterococci Bone and joint infections caused by P. aeruginosa, Enterococci, Bacteroides spp., or anaerobic cocci Indicated for nosocomial pneumonia (moderate to severe) caused by piperacillin-resistant, β-lactamase producing strains of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa (nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside) Community-acquired pneumonia (moderate severity only) caused by piperacillin-resistant, β-lactamase producing strains of H. influenzae Appendicitis (complicated by rupture or abscess) and peritonitis caused by piperacillin-resistant, β-lactamase producing strains of Escherichia coli or the following members of the Bacteroides fragilis group: B. fragilis, B. ovatus, B. thetaiotaomicron, or B. vulgatus Uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses, and ischemic/diabetic foot infections caused by piperacillin-resistant, β-lactamase producing strains of S. aureus Infections caused by piperacillin-susceptible organisms for which piperacillin has been shown to be effective are also amenable to piperacillin tazobactam content. Postpartum endometritis or pelvic inflammatory disease caused by piperacillin-resistant, β-lactamase producing strains of E. coli Route, reduce dose, and Primary mode of elimination: Renal Reduce dose in moderate to severe renal impairment Mode of elimination: 20% in bile, 80% unchanged in urine Reduce dose in moderate to severe renal impairment 1854 LWBK1580-App-J_p indd 1854

4 TABLE J.2 Antipseudomonal Penicillins (Continued ) Spectrum of activity, indications, and active against most strains of Ticarcillin disodium Ticarcillin/ clavulanate Antipseudomonal penicillin Ticarcillin disodium (Antipseudomonal penicillin) + β-lactamase inhibitor clavulanate potassium (the potassium salt of clavulanic acid), for intravenous administration IV: 3 g q6 h Drug interaction with aminoglycosides in renal failure IV: 3.1 g q4 6 h (3.1 g vial containing 3-g ticarcillin and 100-mg clavulanic acid) Moderate infections 200 mg/kg/d in divided doses every 6 h Severe infections 300 mg/kg/d in divided doses every 4 h For patients weighing <60 kg, the recommended dosage is mg/kg/d, based on ticarcillin content, given in divided doses every 4 6 hours. Drug interaction with aminoglycosides in renal failure Ticarcillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative aerobic and anaerobic bacteria. Ticarcillin is, however, susceptible to degradation by β-lactamases, and therefore, the spectrum of activity does not normally include organisms that produce these enzymes. Ticarcillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative aerobic and anaerobic bacteria. Ticarcillin is, however, susceptible to degradation by β-lactamases, and therefore, the spectrum of activity does not normally include organisms that produce these enzymes. Gram-positive aerobes Staphylococcus aureus; Staphylococcus epidermidis Gram-negative aerobes Citrobacter sp.; Enterobacter sp., including E. cloacae; Escherichia coli; Haemophilus influenzae; Klebsiella sp. including K. pneumoniae; Pseudomonas sp. including P. aeruginosa; Serratia marcescens Anaerobic bacteria Bacteroides fragilis group; Prevotella (formerly Bacteroides) melaninogenicus Gram-positive aerobes Staphylococcus saprophyticus; Streptococcus agalactiae (group B); Streptococcus bovis; Streptococcus pneumoniae (penicillin-susceptible strains only); Streptococcus pyogenes; Viridans group streptococci Gram-negative aerobes Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter haemolyticus; Acinetobacter lwoffi; Moraxella catarrhalis; Morganella morganii; Neisseria gonorrhoeae; Pasteurella multocida; Proteus mirabilis; Proteus penneri; Proteus vulgaris; Providencia rettgeri; Providencia stuartii; Stenotrophomonas maltophilia Anaerobic bacteria Clostridium sp. including C. perfringens, C. difficile, C. sporogenes, C. ramosum, and C. bifermentans; Eubacterium sp.; Fusobacterium sp. including F. nucleatum and F. necrophorum; Peptostreptococcus sp.; Veillonella sp. Route, reduce dose, and Primary mode of elimination: Renal Reduce dose in moderate to severe renal impairment Primary mode of elimination: Renal Reduce dose in moderate to severe renal impairment 1855 LWBK1580-App-J_p indd 1855

5 TABLE J.3 Carbapenems Not a substrate/inhibitor of cytochrome P450 enzymes Ertapenem Carbapenem IV/IM: 1 g q24 h Probenecid (decrease clearance of ertapenem) Imipenem/ cilastatin Carbapenem IV: 1,000 mg q6 h (4 g) only in severe life-threatening infections (mainly in some Pseudomonas species) no more than 50 mg/kg/24 h IV: 250 mg q6 h in mild infections IV: 500 mg q8 h (1.5 g) or q6 h (2.0 g) in moderate infections Total dose of sodium 37.5 mg (1.6 meq) by 500-mg imipenem The bactericidal activity of imipenem results from the inhibition of cell wall synthesis Spectrum of activity, indications, and active against most strains of Aerobic and facultative gram-positive micro-organisms Staphylococcus aureus (methicillin-susceptible isolates only); Streptococcus agalactiae; Streptococcus pneumoniae ( penicillin susceptible isolates only); Streptococcus pyogenes Note: Methicillin-resistant Staphylococci and Enterococcus spp. are resistant to ertapenem. Aerobic and facultative gram-positive micro-organisms Escherichia coli; Haemophilus influenzae (β-lactamase negative isolates only); Klebsiella pneumoniae; Moraxella catarrhalis; Proteus mirabilis Anaerobic micro-organisms Bacteroides fragilis; Bacteroides distasonis; Bacteroides ovatus; Bacteroides thetaiotaomicron; Bacteroides uniformis; Clostridium clostridiiforme; Eubacterium lentum; Peptostreptococcus sp.; Porphyromonas asaccharolytica; Prevotella bivia Conditions: Bacterial septicemia. Lower respiratory tract infections. Urinary tract infections (complicated and uncomplicated). Nosocomial pneumonia, peritonitis, sepsis. Gynecologic infections. Bone and joint infections. Skin and skin structure infections. Endocarditis. Polymicrobic infections. Gram-positive aerobes Enterococcus faecalis (formerly S. faecalis) (NOTE: Imipenem is inactive in vitro against Enterococcus faecium [formerly S. faecium]); Staphylococcus aureus including penicillinaseproducing strains; Staphylococcus epidermidis including penicillinase-producing strains; Streptococcus agalactiae (group B streptococci); Streptococcus pneumoniae; Streptococcus pyogenes Gram-negative aerobes Acinetobacter spp.; Citrobacter spp.; Enterobacter spp.; Escherichia coli; Gardnerella vaginalis; Haemophilus influenzae; Haemophilus parainfluenzae Klebsiella spp.; Morganella morganii; Proteus vulgaris; Providencia rettgeri; Pseudomonas aeruginosa (NOTE: Imipenem is inactive in vitro against Xanthomonas [Pseudomonas] maltophilia and some strains of P. cepacia); Serratia spp., including S. marcescens Gram-positive anaerobes Bifidobacterium spp.; Clostridium spp.; Eubacterium spp.; Peptococcus spp.; Peptostreptococcus spp.; Propionibacterium spp. Gram-negative anaerobes Bacteroides spp., including B. fragilis; Fusobacterium spp. Gram-positive aerobes Bacillus spp.; Listeria monocytogenes; Nocardia spp.; Staphylococcus saprophyticus; group C streptococci; group G streptococci; Viridans group streptococci Primary mode of elimination: Renal Reduce dose in moderate to severe renal impairment. Central nervous system adverse experiences such as confusional states, myoclonic activity, and seizures have been reported during treatment with imipenem. Reduce dose in moderate to severe renal impairment. For patients on hemodialysis, imipenem is recommended only when the benefit outweighs the potential risk of seizures LWBK1580-App-J_p indd 1856

6 TABLE J.3 Carbapenems (Continued) Spectrum of activity, indications, and active against most strains of Meropenem Carbapenem IV: 500 mg q8 h Pneumonia, urinary tract infection, gynecologic infections, skin and skin structure infections IV: 1 g q8 h Nosocomial pneumonia, peritonitis, neutropenic patients, sepsis IV: 2 g q8 h Meningitis and cystic fibrosis Gram-negative aerobes Aeromonas hydrophila; Alcaligenes spp.; Capnocytophaga spp.; Haemophilus ducreyi; Neisseria gonorrhoeae including penicillinase-producing strains Pasteurella spp.; Providencia stuartii. Gram-negative anaerobes Prevotella bivia; Prevotella disiens; Prevotella melaninogenica; Veillonella spp. In vitro tests show imipenem to act synergistically with aminoglycoside antibiotics against some isolates of Pseudomonas aeruginosa. Meropenem is a broad-spectrum carbapenem antibiotic. It is active against gram-positive and gram-negative bacteria. Meropenem has significant stability to hydrolysis by β-lactamases of most categories, both penicillinases and cephalosporinases produced by gram-positive and gramnegative bacteria. Meropenem should not be used to treat methicillin-resistant Staphylococcus aureus (MRSA). In vitro tests show meropenem to act synergistically with aminoglycoside antibiotics against some isolates of Pseudomonas aeruginosa. Reduce dose in moderate to severe renal impairment LWBK1580-App-J_p indd 1857

7 TABLE J.4 Monobactams Drug Drug class Usual dose in adults Spectrum of activity, indications, and active against most strains of Aztreonam Monobactam It was originally isolated from Chromobacterium violaceum. IV: 1 2 g q8 h IV: 2 g q6 h Synthetic bactericidal antibiotic Synthetic bactericidal antibiotic Meningeal dose Aerobic gram-negative micro-organisms: Citrobacter spp., including C. freundii; Enterobacter spp., including E. cloacae; Escherichia coli; Haemophilus influenzae (including ampicillin-resistant and other penicillinase-producing strains); Klebsiella, Proteus, and Serratia species. Reduce dose in moderate to severe renal impairment LWBK1580-App-J_p indd 1858

8 TABLE J.5 Cephalosporins (Parenteral) Cefazolin First-generation cephalosporin Cefuroxime Second-generation IV/ oral cephalosporin IV: 1 g q8 h Remember: Na + content = 46 mg per g cefazolin IV: 1.5 g q8 h PO: 500 mg q12 h Remember: Na + content = 2.4 meq/g In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis Drug interactions: None Cefuroxime has in vitro activity against a wide range of grampositive and gramnegative organisms, and it is highly stable in the presence of β-lactamases of certain gram-negative bacteria. The bactericidal action of cefuroxime results from inhibition of cell wall synthesis. Cefotaxime Third-generation cephalosporin IV: 2 g q6 h Administer by IV injection or infusion or by deep IM injection. Spectrum of activity, indications, and active against most strains of Staphylococcus aureus (including penicillinase-producing strains); Staphylococcus epidermidis; Methicillin-resistant staphylococci are uniformly resistant to cefazolin. Group A β-hemolytic Streptococci and other strains of streptococci (many strains of enterococci are resistant) Streptococcus pneumoniae; Escherichia coli; Proteus mirabilis; Klebsiella sp.; Enterobacter aerogenes; Haemophilus influenzae Aerobes, gram-positive Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus pneumoniae; Streptococcus pyogenes (and other streptococci) NOTE: Most strains of enterococci (e.g., Enterococcus faecalis [formerly Streptococcus faecalis]), are resistant to cefuroxime. Methicillin-resistant staphylococci and Listeria monocytogenes are resistant to cefuroxime. Aerobes, gram-negative Citrobacter spp.; Enterobacter spp.; Escherichia coli; Haemophilus influenzae (including ampicillin-resistant strains); Haemophilus parainfluenzae; Klebsiella spp. (including Klebsiella pneumoniae); Moraxella (Branhamella) catarrhalis (including ampicillin- and cephalothin-resistant strains); Morganella morganii (formerly Proteus morganii); Neisseria gonorrhoeae (including penicillinase- and non penicillinase-producing strains); Neisseria meningitidis; Proteus mirabilis; Providencia rettgeri (formerly Proteus rettgeri); Salmonella spp.; Shigella spp. Lower respiratory tract infections, including pneumonia, caused by Streptococcus pneumoniae (formerly Diplococcus pneumoniae), Streptococcus pyogenes a (group A streptococci) and other streptococci (excluding enterococci, e.g., Enterococcus faecalis), Staphylococcus aureus (penicillinase and nonpenicillinase producing), Escherichia coli, Klebsiella sp., Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae, Proteus mirabilis, Serratia marcescens, a Enterobacter sp., indolepositive Proteus and Pseudomonas sp. (including P. aeruginosa). Genitourinary infections Urinary tract infections caused by Enterococcus sp., Staphylococcus epidermidis, Staphylococcus aureus a (penicillinase and nonpenicillinase producing), Citrobacter sp., Enterobacter sp., Escherichia coli, Klebsiella sp., Proteus mirabilis, Proteus vulgaris, a Providencia stuartii, Morganella morganii, a Providencia rettgeri, a Serratia marcescens, and Pseudomonas sp. (including P. aeruginosa). Also, uncomplicated gonorrhea (cervical/urethral and rectal) caused by Neisseria gonorrhoeae, including penicillinase-producing strains. Gynecologic infections, including pelvic inflammatory disease, endometritis, and pelvic cellulitis caused by Staphylococcus epidermidis, Streptococcus sp., Enterococcus sp., Enterobacter species, a Klebsiella sp., a Escherichia coli, Proteus mirabilis, Bacteroides sp. (including Bacteroides fragilis a ), Clostridium sp., and anaerobic cocci (including Peptostreptococcus sp. and Peptococcus sp.) and Fusobacterium sp. (including F. nucleatum a ) Reduce dose in moderate to severe renal impairment. Reduce dose in moderate to severe renal impairment. Do not use for meningitis prophylaxis. Reduce dose in moderate to severe renal impairment. (Continued ) 1859 LWBK1580-App-J_p indd 1859

9 TABLE J.5 Cephalosporins (Parenteral) (Continued) Ceftazidime Third-generation cephalosporin IV: 2 g q8 h Ceftazidime is bactericidal in action, exerting its effect by inhibition of enzymes responsible for cell wall synthesis. Spectrum of activity, indications, and active against most strains of Bacteremia/septicemia caused by Escherichia coli, Klebsiella sp., Serratia marcescens, Staphylococcus aureus, and Streptococcus sp. (including S. pneumoniae) Skin and skin structure infections caused by Staphylococcus aureus (penicillinase and nonpenicillinase producing), Staphylococcus epidermidis, Streptococcus pyogenes (group A streptococci) and other streptococci, Enterococcus sp., Acinetobacter species, a Escherichia coli, Citrobacter species (including C. freundii a ), Enterobacter sp., Klebsiella sp., Proteus mirabilis, Proteus vulgaris, a Morganella morganii, Providencia rettgeri, a Pseudomonas sp., Serratia marcescens, Bacteroides sp., and anaerobic cocci (including Peptostreptococcus a sp. and Peptococcus sp.) Intra-abdominal infections including peritonitis caused by Streptococcus sp., a Escherichia coli, Klebsiella sp., Bacteroides sp., and anaerobic cocci (including Peptostreptococcus a sp. and Peptococcus a sp.) Proteus mirabilis, a and Clostridium species a Bone and/or joint infections caused by Staphylococcus aureus (penicillinase- and non penicillinase-producing strains), Streptococcus sp. (including S. pyogenes a ), Pseudomonas sp. (including P. aeruginosa a ), and Proteus mirabilis a Central nervous system infections (e.g., meningitis and ventriculitis), caused by Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae, a and Escherichia coli a Lower respiratory tract infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp.; Haemophilus influenzae, including ampicillin-resistant strains; Klebsiella spp.; Enterobacter spp.; Proteus mirabilis; Escherichia coli; Serratia spp.; Citrobacter spp.; Streptococcus pneumoniae; and Staphylococcus aureus (methicillin-susceptible strains). Skin and skin structure infections caused by Pseudomonas aeruginosa; Klebsiella spp.; Escherichia coli; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Enterobacter spp.; Serratia spp.; Staphylococcus aureus (methicillin-susceptible strains); and Streptococcus pyogenes (group A β-hemolytic streptococci). Urinary tract infections, both complicated and uncomplicated, caused by Pseudomonas aeruginosa; Enterobacter spp.; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Klebsiella spp.; and Escherichia coli Bacterial septicemia caused by Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, Escherichia coli, Serratia spp., Streptococcus pneumoniae, and Staphylococcus aureus (methicillin-susceptible strains) Bone and joint infections caused by Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., and Staphylococcus aureus (methicillin-susceptible strains) Reduce dose in moderate to severe renal impairment LWBK1580-App-J_p indd 1860

10 TABLE J.5 Cephalosporins (Parenteral) (Continued) Spectrum of activity, indications, and active against most strains of Cefepime Fourth-generation cephalosporin IV: 1 2 g q12 h For proven serious systemic P. aeruginosa infections, febrile neutropenia, or cystic fibrosis: 2 g (IV) q8 h (max dose) Meningeal dose: 2 g (IV) q8 h (max dose) Local intolerances to IV or IM administration of cefepime were not statistically different from those of ceftazidime administration Gynecologic infections, including endometritis, pelvic cellulitis, and other infections of the female genital tract caused by Escherichia coli Intra-abdominal infections, including peritonitis caused by Escherichia coli, Klebsiella spp., and Staphylococcus aureus (methicillin-susceptible strains) and polymicrobial infections caused by aerobic and anaerobic organisms and Bacteroides spp. (many strains of Bacteroides fragilis are resistant) Central nervous system infections, including meningitis, caused by Haemophilus influenzae and Neisseria meningitidis. Ceftazidime has also been used successfully in a limited number of cases of meningitis due to Pseudomonas aeruginosa and Streptococcus pneumoniae. In vitro, activity against gram-positive organisms including Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and penicillin-susceptible Staphylococcus aureus The broad range of gram-negative organisms sensitive to include family Enterobacteriaceae, Klebsiella pneumoniae, Haemophilus influenza, Neisseria meningitidis, Neisseria gonorrhoeae, and Pseudomonas aeruginosa a Usual dose, assumes normal renal/hepatic function. Reduce dose in moderate to severe renal impairment 1861 LWBK1580-App-J_p indd 1861

11 TABLE J.6 Glycopeptides Spectrum of activity, indications, and active against most strains of Vancomycin Glycopeptide The initial dose should be no <15 mg/kg, even in patients with mild to moderate renal insufficiency IV: 1 g q12 h The bactericidal action of vancomycin results primarily from inhibition of cell wall biosynthesis. In addition, vancomycin alters bacterial cell membrane permeability and RNA synthesis. Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histaminelike flushing and anaphylactoid reactions. Indicated for the treatment of serious or severe infections caused by susceptible strains of methicillinresistant (β-lactam resistant) staphylococci. It is indicated for penicillin-allergic patients; for patients who cannot receive or who have failed to respond to other drugs, including the penicillins or cephalosporins; and for infections caused by vancomycinsusceptible organisms that are resistant to other antimicrobial drugs. Also indicated for initial therapy when methicillin-resistant staphylococci are suspected, but after susceptibility data are available, therapy should be adjusted accordingly. Effective in the treatment of Staphylococcal endocarditis. Its effectiveness has been documented in other infections due to staphylococci, including septicemia, bone infections, lower respiratory tract infections, and skin and skin structure infections. Effective alone or in combination with an aminoglycoside for endocarditis caused by S. viridans or S. bovis. For endocarditis caused by enterococci (e.g., E. faecalis), vancomycin hydrochloride has been reported to be effective only in combination with an aminoglycoside. Effective for the treatment of diphtheroid endocarditis Has been used successfully in combination with rifampin, an aminoglycoside, or both, in early-onset prosthetic valve endocarditis caused by S. epidermidis or diphtheroids The parenteral form of vancomycin may be administered orally for the treatment of antibioticassociated pseudomembranous colitis produced by C. difficile and for staphylococcal enterocolitis Dosage adjustment must be made in patients with impaired renal function. Vancomycin dosage schedules should be adjusted in elderly patients Dosage table for vancomycin (Adapted from Moellering et al.) b Creatine Clearance/Dose ml/min mg/24 h 100 1, , , , LWBK1580-App-J_p indd 1862

12 TABLE J.7 Chloramphenicol, Clindamycin, Erythromycin Group, Ketolides Chloramphenicol Chloramphenicol sodium succinate Chloramphenicol sodium succinate is intended for intravenous use only. It has been demonstrated to be ineffective when given intramuscularly g IV q6 h (max of 4 g/d) Administration of 50 mg/kg/d in divided doses will produce blood levels of the magnitude to which the majority of susceptible micro-organisms will respond. The most serious adverse effect of chloramphenicol is bone marrow depression. Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia) are known to occur after the administration of chloramphenicol. Clindamycin Clindamycin phosphate IV or IM: mg q8 h PO: g q6 h Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clindamycin, and may range in severity from mild to life threatening. Spectrum of activity, indications, and active against most strains of Chloramphenicol must be used only in those serious infections for which less potentially dangerous drugs are ineffective or contraindicated: 1. Acute infections caused by Salmonella typhi 2. Serious infections caused by susceptible strains: Salmonella sp. H. influenzae, especially meningeal infections Rickettsia Lymphogranuloma-psittacosis group Various gram-negative bacteria causing bacteremia, meningitis, or other serious gram-negative infections Other susceptible organisms that have been demonstrated to be resistant to all other appropriate antimicrobial agents 3. Cystic fibrosis regimens Aerobic gram-positive cocci, including: Staphylococcus aureus (penicillinase and non penicillinase-producing strains); Staphylococcus epidermidis (penicillinase- and non penicillinase-producing strains); Streptococci (except Enterococcus faecalis); Pneumococci Anaerobic gram-negative bacilli, including Bacteroides sp. (including Bacteroides fragilis group and Bacteroides melaninogenicus group) and Fusobacterium species Anaerobic gram-positive non spore-forming bacilli, including Propionibacterium, Eubacterium, and Actinomyces sp. Anaerobic and microaerophilic gram-positive cocci, including Peptococcus sp., Peptostreptococcus sp., Microaerophilic streptococci, and Clostridia Total urinary excretion of chloramphenicol in these studies ranged from a low of 68% to a high of 99% over a 3-day period. From 8% to 12% of the antibiotic excreted is in the form of free chloramphenicol The elimination half-life of clindamycin is increased slightly in patients with markedly reduced renal or hepatic function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. (Continued ) 1863 LWBK1580-App-J_p indd 1863

13 TABLE J.7 Chloramphenicol, Clindamycin, Erythromycin Group, Ketolides (Continued) Spectrum of activity, indications, and active against most strains of Clarithromycin Semi-synthetic macrolide antibiotic Linezolid Oxazolidinone PO or IV: 600 mg q12 h all indications except 400 mg q12 h for uncomplicated skin infections PO: 0.5 g q12 h Drug Interactions: Patients who are receiving single doses of clarithromycin and theophylline or carbamazepine may be associated with an increase of serum theophylline and carbamazepine concentrations. Reversible myelosuppression including anemia, leukopenia, pancytopenia, and thrombocytopenia has been reported in patients. In cases where the outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment levels. Lactic acidosis has been reported with the use of linezolid. Spontaneous reports of serotonin syndrome associated with the coadministration of linezolid and serotonergic agents, including antidepressants Peripheral and optic neuropathy have been reported in patients treated with Linezolid Aerobic gram-positive micro-organisms Staphylococcus aureus; Streptococcus pneumoniae; Streptococcus pyogenes Aerobic gram-negative micro-organisms Haemophilus influenzae; Haemophilus parainfluenzae; Moraxella catarrhalis Other micro-organisms Mycoplasma pneumoniae; Chlamydia pneumoniae Mycobacteria Mycobacterium avium complex consisting of Mycobacterium avium and Mycobacterium intracellulare β-lactamase production should have no effect on clarithromycin activity. Most strains of methicillin-resistant and oxacillinresistant staphylococci are resistant to clarithromycin. Helicobacter Helicobacter pylori Aerobic and facultative gram-positive micro-organisms Enterococcus faecium (vancomycin-resistant strains only); Staphylococcus aureus (including methicillin-resistant strains); Streptococcus agalactiae; Streptococcus pneumoniae (including multidrug-resistant isolates); Streptococcus pyogenes Aerobic and facultative gram-positive micro-organisms Enterococcus faecalis (including vancomycinresistant strains); Enterococcus faecium (vancomycin-susceptible strains); Staphylococcus epidermidis (including methicillin-resistant strains); Staphylococcus haemolyticus; Viridans group streptococci Aerobic and facultative gram-negative micro-organisms Pasteurella multocida Contraindications: Any of the following drugs: cisapride, pimozide, astemizole, terfenadine, and ergotamine or dihydroergotamine. If clarithromycin is coadministered with cisapride, pimozide, astemizole, or terfenadine resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes), this is most likely due to inhibition of metabolism of these drugs. Linezolid is primarily metabolized by oxidation of the morpholine ring, which results in two inactive ring-opened carboxylic acid metabolites: The aminoethoxyacetic acid metabolite (A) and the hydroxyethyl glycine metabolite (B). Nonrenal clearance accounts for approximately 65% of the total clearance of linezolid. Under steady-state conditions, approximately 30% of the dose appears in the urine as linezolid, 40% as metabolite B, and 10% as metabolite A LWBK1580-App-J_p indd 1864

14 TABLE J.8 Tetracyclines and others Spectrum of activity, indications, and active against most strains of Doxycycline Derived from oxytetracycline PO: 0.1 g q12 h IV: 0.1 g q12 h Oxytetracycline Tetracycline PO: g q6 h IV: g q12 h The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. Wide range of gram-positive and gram-negative micro-organisms Aerobic gram-positive micro-organisms Bacillus anthracis; Listeria monocytogenes; Staphylococcus aureus Aerobic gram-negative micro-organisms Bartonella bacilliformis; Brucella sp.; Calymmatobacterium granulomatis; Campylobacter fetus; Francisella tularensis; Haemophilus ducreyi; Haemophilus influenzae; Neisseria gonorrhoeae; Vibrio cholerae; Yersinia pestis. Anaerobic micro-organisms Actinomyces israelii; Fusobacterium fusiforme; Clostridium sp. Other micro-organisms Borrelia recurrentis; Chlamydia psittaci; Chlamydia trachomatis; Mycoplasma pneumoniae; Rickettsiae; Treponema pallidum; Treponema pertenue Primarily bacteriostatic Wide range of gram-positive and gram-negative micro-organisms, similar to other tetracyclines Can be used in patients with renal failure Hemodialysis does not alter serum half-life. Contraindicated in pregnancy, hepatotoxicity in mother, transplacental to fetus. Intravenous dosage over 2.0 g/d may be associated with fatal hepatotoxicity 1865 LWBK1580-App-J_p indd 1865

15 TABLE J.9 Fluoroquinolones Drug Drug class Usual dose in adults Ciprofloxacin Fluoroquinolone IV: 400 mg q8 12 h ( infusion over a period of 60 min) PO: mg q12 h Inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair, and recombination Drug interactions with theophylline, caffeine, warfarin phenytoin, sulfonylurea glyburide, metronidazole, probenecid, piperacillin sodium, and cyclosporine Levofloxacin Fluoroquinolone mg qd PO or IV Inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair, and recombination Drug interactions with theophylline, caffeine, warfarin, phenytoin, sulfonylurea glyburide, metronidazole, probenecid, piperacillin sodium, and cyclosporine Spectrum of activity, indications, and active against most strains of Aerobic gram-positive micro-organisms Enterococcus faecalis (many strains are only moderately susceptible); Staphylococcus aureus (methicillin-susceptible strains only); Staphylococcus epidermidis (methicillin-susceptible strains only); Staphylococcus saprophyticus; Staphylococcus pneumoniae (penicillin-susceptible strains); Staphylococcus pyogenes Aerobic gram-negative micro-organism Citrobacter (diversus, freundii); Enterobacter cloacae; Escherichia coli; Haemophilus (influenzae, parainfluenzae); Klebsiella pneumoniae; Moraxella catarrhalis; Morganella morganii; Proteus (mirabilis, vulgaris), Providencia (rettgeri, stuartii); Pseudomonas aeruginosa; Serratia marcescens. Also ciprofloxacin has been shown to be active against Bacillus anthracis both in vitro and by use of serum levels as a surrogate marker. Acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis Acute bacterial exacerbation of chronic bronchitis due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis. Nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an antipseudomonal β-lactam is recommended. Community-acquired pneumonia due to Staphylococcus aureus, Streptococcus pneumoniae (including multidrug-resistant strains [MDRSP]), a Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae Contraindications: Concomitant administration with tizanidine Patients with impaired renal function: Creatinine clearance (ml/min): >30 (see usual dose) 5 29 ( mg q18 24 h) Clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in patients with impaired renal function (creatinine clearance <50 ml/min), requiring dosage adjustment in such patients to avoid accumulation. Neither hemodialysis nor continuous ambulatory peritoneal dialysis (CAPD) is effective in removal of levofloxacin from the body, indicating that supplemental doses of levofloxacin are not required following hemodialysis or CAPD. Adverse reactions: Opiate screen false positives; photosensitivity; QTc interval prolongation and tendinopathy 1866 LWBK1580-App-J_p indd 1866

16 TABLE J.9 Fluoroquinolones (Continued) Drug Drug class Usual dose in adults Spectrum of activity, indications, and active against most strains of Moxifloxacin Fluoroquinolone 400 mg PO or IV qd The bactericidal action of moxifloxacin results from the interference with topoisomerase II and IV Complicated skin and skin structure infections due to methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, or Porteus mirabilis. Uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulites, furuncles, impetigo, pyoderma, and wound infections, due to Staphylococcus aureus or Streptococcus pyogenes Chronic bacterial prostatitis due to Escherichia coli, Enterococcus faecalis, or Staphylococcus epidermidis Complicated urinary tract infections (mild to moderate) due to Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa Acute pyelonephritis (mild to moderate) caused by Escherichia coli Uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus Community-acquired pneumonia (CAP), including CAP caused by multidrug-resistant Streptococcus pneumoniae b Complicated skin and skin structure infections, including diabetic foot infections Complicated intra-abdominal infections, including polymicrobial infections such as abscesses Similar to other fluoroquinolones a MDRSP (multidrug-resistant Streptococcus pneumoniae) are strains resistant to two or more of the following antibiotics: penicillin (minimum inhibitory concentration [MIC] = 2 μg/ml), second-generation cephalosporins (e.g., cefuroxime, macrolides, tetracyclines, and trimethoprim/sulfamethoxazole). b Multidrug-resistant S. pneumoniae includes isolates previously known as PRSP (penicillin-resistant S. pneumoniae), and are strains resistant to two or more of the following antibiotics: Penicillin (MIC 2 mg/ml), second-generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole LWBK1580-App-J_p indd 1867

17 TABLE J.10 Polymyxins Spectrum of activity, indications, and active against most strains of Polymyxin B Phospholipid cell membranealtering antibiotic Polymyxin E Colistin (polymyxin E) is a polymyxin antibiotic produced by certain strains of Bacillus polymyxa var. colistinus. Two forms of colistin available commercially: colistin sulfate and colistimethate sodium (colistin methanesulfonate sodium, colistin sulfomethate sodium) mg/kg (IV) q12 h (1 mg = 10,000 units) Colomycin 1,000,000 units is 80-mg colistimethate Coly-mycin M 150 mg colistin base is 360-mg colistimethate, or 4,500,000 units Colistin is polycationic and has both hydrophilic and lipophilic moieties. These interact with the bacterial cytoplasmic membrane, changing its permeability. This effect is bactericidal. The main toxicities described with intravenous treatment are nephrotoxicity and neurotoxicity. At a dose of 160 mg colistimethate IV q8 h, very little nephrotoxicity is seen. Polymyxins bind to the cell membrane and alter its structure making it more permeable. The resulting water uptake leads to cell death. They are cationic, basic proteins that act like detergents. Interactions: Amphotericin B, amikacin, gentamicin, tobramycin, vancomycin. Adverse effects: Renal failure (tubular necrosis). Neurotoxicity associated with very prolonged or high serum levels; neuromuscular blockade with renal failure and or neuromuscular disorders Colistin is effective against gramnegative bacilli, except Proteus and Burkholderia cepacia, and is used as a polypeptide antibiotic. Multidrug-resistant Acinetobacter baumanii, even in Acinetobacter meningitis with intrathecal polymyxin E Mycobacterium aurum is susceptible to the antibiotic colistin (polymyxin E), which has an MIC of 5 μg/ml and an apparent bactericidal effect at concentrations >50 μg/ml. Bactericidal for gram-negative; little to no effect on gram-positive since cell wall is too thick to permit access to membrane Usage in pregnancy: The safety of this drug in human pregnancy has not been established. Colistin sulfate and colistimethate sodium are eliminated from the body by different routes LWBK1580-App-J_p indd 1868

18 TABLE J.11 Aminoglycosides Spectrum of activity, indications, and active against most strains of Gentamicin Aminoglycoside antibiotic, derived from Micromonospora purpurea, an actinomycete Amikacin Semi-synthetic aminoglycoside antibiotic, derived from kanamycin Tobramycin Aminoglycoside antibiotic, derived from the actinomycete Streptomyces tenebrarius Intravenous use only for gentamicin sulfate in 0.9% sodium chloride. Gentamicin sulfate IV: 3 mg/kg/d q8 h In patients with lifethreatening infections: 5 mg/kg/d q24 h (preferred over q8 h dosing) Amikacin sulfate IV: 15 mg/kg or 1 g q24 h (preferred to q12 h dosing) Tobramycin sulfate: IV: 5 mg/kg q24 h or 240 mg q24 h (preferred over q8 h dosing). The dosage should be reduced to 3 mg/kg/d as soon as clinically indicated. Bactericidal antibiotic that acts by inhibiting normal protein synthesis in susceptible micro-organisms Drug interactions: Amphotericin B, cephalothin, cyclosporine, enflurane, methoxyflurane, polymyxin B, radiographic contrast, vancomycin (increase nephrotoxicity), cisplatinum, etc. (see specifications of the product) Drug interactions: Amphotericin B, cephalothin, cyclosporine, enflurane, methoxyflurane, polymyxin B, radiographic contrast, vancomycin (increase nephrotoxicity), cisplatinum, etc. (see specifications of the product) Tobramycin acts by inhibiting synthesis of protein in bacterial cells. Drug interactions: Amphotericin B, cephalothin, cyclosporine, enflurane, methoxyflurane, polymyxin B, radiographic contrast, vancomycin (increase nephrotoxicity), cisplatinum, etc. (see specifications of the product) Escherichia coli; Proteus sp. (indole-positive and indole-negative); Pseudomonas aeruginosa; species of Klebsiella-Enterobacter- Serratia group; Citrobacter sp.; and Staphylococcus sp. (including penicillin and methicillin-resistant strains) Gentamicin is also active in vitro against species of Salmonella and Shigella. Gram negative Amikacin is active in vitro against Pseudomonas sp., Escherichia coli, Proteus sp. (indolepositive and indole-negative), Providencia sp., Klebsiella-Enterobacter-Serratia sp., Acinetobacter (formerly Mima-Herellea) sp., and Citrobacter freundii When strains of the above organisms are found to be resistant to other aminoglycosides, including gentamicin, tobramycin, and kanamycin, many are susceptible to amikacin in vitro. Gram positive Amikacin is active in vitro against penicillinase and non penicillinase-producing Staphylococcus sp. including methicillinresistant strains. However, aminoglycosides in general have a low order of activity against other gram-positive organisms. Gram-positive aerobes Staphylococcus aureus Gram-negative aerobes Citrobacter sp., Enterobacter sp., Escherichia coli, Klebsiella sp., Morganella morganii, Pseudomonas aeruginosa, Proteus mirabilis, Proteus vulgaris, Providencia sp., Serratia sp. Aminoglycosides have a low order of activity against most gram-positive organisms, including Streptococcus pyogenes, Streptococcus pneumoniae, and Enterococci To adjust the doses for patients with renal impairment Adverse reactions: Nephrotoxicity: Adverse renal effects have been reported. They occur more frequently in patients with a history of renal impairment and in patients treated for longer periods or with larger dosages than recommended. Others such as neurotoxicity (serious adverse effects on both vestibular and auditory branches of the eighth nerve), peripheral neuropathy, or encephalopathy, including numbness, skin tingling, muscle twitching, convulsions, and a myasthenia gravis-like syndrome, have been reported (see specifications of the product). See gentamicin sulfate. See gentamicin sulfate LWBK1580-App-J_p indd 1869

19 TABLE J.12 Miscellaneous Drug Drug class Usual dose in adults Spectrum of activity, indications, and active against most strains of Metronidazole Nitroimidazole antiparasitic/ antibiotic Trimethoprim (TMP)/ sulfamethoxazole (SMX) or cotrimoxazole Synthetic folate antagonist/ sulfonamide IV: 1 g q/24 h PO: 500 mg q12 h IV or PO: mg/kg q6 h Metronidazole is a synthetic antibacterial compound. Drug interactions: Warfarin and other oral coumarin anticoagulants, phenytoin or phenobarbital, cimetidine, and disulfiram Sulfamethoxazole is bacteriostatic and trimethoprim is bactericidal Drug interactions: Warfarin (monitoring carefully); phenytoin (folate deficiencies when is used concomitantly); thiazides increased incidence of thrombocytopenia with purpura in elderly patients; cyclosporine (nephrotoxicity reversible); digoxin; indomethacin; pyrimethamine; tricyclic antidepressants; amantadine; methotrexate; and oral hypoglycemic agents Anaerobic gram-negative bacilli, including Bacteroides sp., including the Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus); Fusobacterium sp. Anaerobic gram-positive bacilli, including Clostridium sp. and susceptible strains of Eubacterium Anaerobic gram-positive cocci, including Peptococcus sp.; Peptostreptococcus sp. Primary agent in the treatment of Pneumocystis carinii pneumonia (PCP), an opportunistic infection in patients with HIV/AIDS, and as secondary prophylaxis of PCP in patients who have already had at least one episode of PCP. Also is indicated for the treatment of chronic bronchitis, enterocolitis caused by strains of Shigella (flexneri and sonnei), acute otitis media in children, traveler s diarrhea caused by enterotoxigenic Escherichia coli and Shigella sp., and bacterial urinary tract infections Primary mode of elimination: Hepatic SMX-TMP is metabolized in the liver. Urinary concentrations of both active drugs are decreased in patients with impaired renal function. Only small amounts of trimethoprim are excreted in feces via biliary elimination. Trimethoprim and active sulfamethoxazole are moderately removed by hemodialysis LWBK1580-App-J_p indd 1870

20 TABLE J.13 Antifungals Amphotericin B Antifungal Polyene macrolide antibiotic produced by soil bacteria Streptomyces nodosus IV: mg/kg q24 h Amphotericin B is the gold standard for the treatment of serious and invasive systemic mycosis as well as for kala azar. Drug interactions: Avoid concomitant administration of nephrotoxic drugs and bone marrow suppressants. Liposomal amphotericin B Antifungal Polyene macrolide antibiotic True liposomal preparation of amphotericin B in which lipid complex of liposomes is constituted of lecithin and cholesterol IV: 3 6 mg/kg q24 h Is the most effective and affordable drug for treatment of both systemic mycosis and kala azar. Drug interactions: As with conventional amphotericin B, avoid concomitant administration of nephrotoxic drugs and bone marrow suppressants, only and in patients with hypokalemia. Spectrum of activity, indications, and active against most strains of Amphotericin B has useful activity against candidiasis, cryptococcosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, coccidioidomycosis, aspergillosis, extracutaneous sporotrichosis, zygomycosis (mucormycosis), penicilliosis (Penicilliosis marneffei) pseudallescheriasis, hyalohyphomycosis (including infection due to Acremonium, Fusarium, Penicillium, etc.) and phaeohyphomycosis (including infection due to Alternaria, Bipolaris, Cladosporium, Cladophialophora, Curvularia, Exophiala, Exserohilum, Fonsecaea, Phialophora, Wangiella, etc.). Empirical antifungal therapy is useful to granulocytopenic patients with persistent or recurrent fever. a Amphotericin B shows a high order of in vitro activity against many species of fungi viz. Histoplasma capsulatum, Cryptococcus immitis, Candida sp., Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenckii, Mucor sp., Aspergillus fumigatus, Malassezia furfur, Trichosporon beigelii, Saccharomyces cerevisiae, Scedosporium sp., Paecilomyces sp., Penicillium sp., Fusarium sp., Bipolaris sp., Exophiala sp., Cladophialophora sp., Absidia sp., Apophysomyces sp., Cunninghamella sp., Rhizomucor sp., Rhizopus sp., and Saksenaea sp. These fungi are inhibited by concentrations of amphotericin B ranging from 0.03 to 1 μg/ml in vitro. Amphotericin B also has activity against species of Leishmania and is found to be effective in the treatment of Kala-Azar. Primary mode of elimination: Metabolized The most common cause for withdrawal of or failure to continue amphotericin B therapy is its severe renal toxicity in nearly half of all the patients. The second problem, which is a major one, is the nephrotoxicity of amphotericin B. Primary mode of elimination: Metabolized (Continued ) 1871 LWBK1580-App-J_p indd 1871