PRINTER-FRIENDLY VERSION AT PHARMACYPRACTICENEWS.COM Antimicrobial Efficacy JARED L. CRANDON, PHARMD, BCPS Associate Director JOSEPH L. KUTI, PHARMD Associate Director DAVID P. NICOLAU, PHARMD, FCCP, FIDSA Director Center for Anti-Infective e Research and Development Hartford Hospital Hartford, Connecticut This review is intended d to be a reference to describe the potential ti in vivo activity of various antimicrobial agents when the identity of the infecting organism is known. Because the early initiation of appropriate therapy has been noted to improve clinical outcomes for serious infections, empiric therapy frequently demands broad-spectrum antimicrobial agent(s) until the specific infecting bacterium has been identified. Given the continuing concerns of increasing antimicrobial resistance among gram-positive and gram-negative bacteria and the lack of new antibiotics coming to market, knowledge of microbiologic activity and clinical treatment guidelines increases the likelihood of providing appropriate antimicrobial therapy to patients and minimizes the use of unnecessary agents. Importantly, antimicrobial susceptibilities can be highly variable based on institution-specific and geographic factors (including various institutional sites eg, outpatient vs inpatient, intensive care unit vs ward). Therefore, an awareness of local susceptibility data is essential to ensure the highest probability of successful clinical outcomes. While the use of various dosing techniques, especially for β-lactams, may potentiate in vivo activity, the information contained herein pertains only to standard dosing regimens. This review reflects the opinions of the authors and is intended to be a general guide to antimicrobial applications with the appreciation that host factors (eg, site of infection, clinical picture, comorbid conditions) could greatly impact antimicrobial selection. PHARMACY PRACTICE NEWS AUGUST 2011 1
Table 1. Penicillins & Related Antimicrobials Nonantipseudomonal Amoxicillin Ampicillin Penicillin G Penicillin V Ticarcillin Piperacillin Antipseudomonal Ticarcillin-Clavulanate Aztreonam Piperacillin-Tazobactam Imipenem-Cilastatin Meropenem Doripenem Antistaphylococcal Cloxacillin/Dicloxacillin Nafcillin/Oxacillin Amoxicillin-Clavulanate Others Ampicillin-Sulbactam Ertapenem Chlamydia Moraxella catarrhalis 2 2 2 2 2 2 1 1 2 Neisseria gonorrhoeae a 3 3 2 2 2 2 2 2 2 2 Neisseria meningitidis 1 2 2 2 2 2 2 2 2 2 Chlamydia pneumoniae (TWAR) Chlamydia psittaci Chlamydia trachomatis Aerobes Other Bacilli (nonenterobacteriaceae) Enterobacteriaceae Coccobacilli Bordetella pertussis 3 3 3 3 Brucella spp. b Campylobacter jejuni 3 2 2 2 3 Francisella tularensis Helicobacter pylori c 1 Hemophilus ducreyi 2 2 2 Hemophilus influenzae d 3 3 3 3 3 2 2 2 2 2 2 1 1 2 Legionella pneumophila Citrobacter spp. e 2 2 2 2 2 2 1 1 1 1 Enterobacter spp. e,f 1 1 1 2 2 2 1 1 1 1 Escherichia coli f,g 3 3 2 3 2 2 2 2 2 2 2 2 2 2 Klebsiella pneumoniae f,g 2 2 2 2 2 2 2 2 2 2 2 Morganella morganii 2 2 2 2 2 2 2 2 2 2 Proteus mirabilis 1 1 2 2 2 2 2 2 2 2 2 2 2 2 Proteus vulgaris 2 2 2 2 2 2 2 2 2 Providencia stuartii 2 2 2 2 2 2 2 2 Salmonella spp. 3 2 3 2 2 2 2 2 2 2 2 2 1 Salmonella typhi 3 3 3 3 2 2 2 2 Serratia spp. 2 2 2 2 2 2 2 2 1 Shigella spp. 2 2 3 3 3 2 3 2 2 2 3 2 Acinetobacter spp. h 2 2 2 2 2 2 2 Burkholderia (Pseudomonas) cepacia h 3 3 3 3 1 2 Pseudomonas aeruginosa h 3 1 2 2 1 1 1 1 Stenotrophomonas (Xanthomonas) maltophilia 3 3 2 3 Pasteurella multocida 2 2 1 1 2 2 2 2 2 2 2 1 2 Vibrio cholerae 3 3 Key to Table 1 2 3 First-line agent based on clinical efficacy, susceptibility patterns, and consideration of antimicrobial stewardship and the cost of care. Indicates an alternative drug based on clinical efficacy and susceptibility patterns. Indicates a drug with a low level of activity against this organism, and/or limited clinical efficacy. Either there is insufficient clinical data or this drug should not be used for this organism. 2
Table 1. Penicillins & Related Antimicrobials (continued) Nonantipseudomonal Amoxicillin Ampicillin Penicillin G Penicillin V Ticarcillin Piperacillin Antipseudomonal Ticarcillin-Clavulanate Aztreonam Piperacillin-Tazobactam Imipenem-Cilastatin Meropenem Doripenem Antistaphylococcal Cloxacillin/Dicloxacillin Nafcillin/Oxacillin Amoxicillin-Clavulanate Others Ampicillin-Sulbactam Ertapenem Aerobes Anaerobes Bacilli Methicillin-susceptible Staphylococcus epidermidis 2 2 2 2 2 2 2 2 2 2 Methicillin-resistant Staphylococcus epidermidis Streptococcus Group A (S. pyogenes) 1 1 1 1 2 2 2 2 2 2 2 3 3 2 2 2 Streptococcus Group B (S. agalactiae) 1 1 1 1 2 2 2 2 2 2 2 3 3 2 2 2 Streptococcus Group D (eg, S. bovis) 1 1 1 1 2 2 2 2 2 2 2 3 3 2 2 Streptococcus pneumoniae i 1 1 1 1 2 2 2 2 2 2 2 3 3 2 2 2 Penicillin-resistant Streptococcus pneumoniae j,k 2 k 2 2 2 2 k 2 Viridans streptococci 3 3 3 3 2 2 2 2 2 2 2 2 3 3 2 Actinomycetes Actinomyces israelii 1 1 1 2 2 2 Nocardia spp. 3 3 3 3 Bacillus anthracis l 2 2 2 Corynebacterium diphtheriae m 2 Corynebacterium jeikeium 2 Gardnerella vaginalis n 2 Listeria monocytogenes o 1 1 2 2 2 2 2 3 3 3 2 2 Bacteroides fragilis 3 3 2 1 1 1 1 2 1 1 Fusobacterium spp. 2 2 2 2 3 2 3 2 2 2 2 2 2 2 Prevotella melaninogenica 3 3 3 3 3 2 2 2 2 2 2 2 2 Clostridium difficile p Clostridium perfringens 2 2 1 1 2 2 2 2 2 2 2 2 2 2 Clostridium tetani 2 2 2 2 2 2 2 2 2 2 2 2 2 Peptostreptococcus spp. 2 2 1 1 2 2 2 2 2 2 2 2 2 2 Mycoplasma pneumoniae Ureaplasma urealyticum Borrelia burgdorferi (Lyme disease) q 1 Borrelia recurrenis 2 Leptospira spp. 2 1 1 2 Treponema pallidum 1 Myco plasma Spiral Organisms Enterococcus Enterococcus faecalis 1 1 1 2 2 2 3 3 3 2 2 Vancomycin-resistant Enterococcus faecalis Enterococcus faecium 3 3 3 3 3 3 3 3 3 3 3 Vancomycin-resistant Enterococcus faecium Methicillin-susceptible Staphylococcus aureus 2 2 2 2 2 1 1 2 2 2 Methicillin-resistant Staphylococcus aureus Glycopeptide-intermediate susceptible Staphylococcus aureus 3
Table 2. Aminoglycosides, Macrolides, Quinolones, & Other Antibiotics Aminoglycosides Macrolides Quinolones r Other Antibiotics UTI Agents u Amikacin Gentamicin Streptomycin Tobramycin Azithromycin Clarithromycin Dirithromycin Erythromycin Ciprofloxacin Gemifloxacin Levofloxacin Moxifloxacin Chloramphenicol Clindamycin Colistin/Polymixin B Daptomycin s Fidoxamicin Linezolid Metronidazole Quinupristin-Dalfopristin Rifampin Telavancin Telithromycin Tetracyclines (eg, Doxycycline) t Tigecycline Trimethoprim-Sulfamethoxazole Vancomycin Fosfomycin Nitrofurantoin Norfloxacin Aerobes Aerobes Other Bacilli (Nonenterobacteriaceae) Enterobacteriaceae Coccobacilli 3 3 2 1 Moraxella catarrhalis 3 3 3 1 1 2 2 2 2 2 2 3 3 2 2 3 2 1 Neisseria gonorrhoeae a 2 3 2 2 2 2 3 3 Neisseria meningitidis 2 3 2 2 2 2 2 3 Chlamydia pneumoniae (TWAR) 2 2 2 2 2 2 2 2 2 2 2 Chlamydia Chlamydia psittaci 1 1 2 1 2 3 2 Chlamydia trachomatis 1 2 2 3 2 2 3 2 1 3 3 Bordetella pertussis 1 1 1 2 3 3 2 2 2 3 Brucella spp. b 2 3 3 3 3 2 1 1 2 Campylobacter jejuni 2 2 2 2 2 2 3 3 2 2 Francisella tularensis 1 1 3 2 2 Helicobacter pylori c 1 1 1 Hemophilus ducreyi 2 2 2 2 3 3 2 Hemophilus influenzae d 3 3 3 1 1 3 3 2 2 2 2 2 2 2 2 2 1 2 Legionella pneumophila 1 1 2 1 1 2 1 1 3 2 2 2 2 2 Citrobacter spp. e 2 1 1 2 2 2 3 2 2 3 3 3 Enterobacter spp. e 2 1 1 2 2 2 2 2 3 3 2 Escherichia coli f 2 1 1 2 2 2 3 2 3 3 2 3 2 2 2 Klebsiella pneumoniae f 2 1 1 2 3 2 2 3 2 2 2 3 3 2 Morganella morganii 2 1 1 2 2 2 2 2 3 3 Proteus mirabilis 2 1 1 2 2 2 3 3 2 3 2 2 Proteus vulgaris 2 1 1 2 2 2 3 3 2 3 3 2 Providencia stuartii 2 2 2 2 2 3 2 3 2 Salmonella spp. 2 2 2 2 2 2 2 2 2 2 Salmonella typhi 1 2 2 2 Serratia spp. 2 1 2 2 2 3 3 3 2 2 3 3 3 Shigella spp. 3 3 3 2 2 2 3 3 2 2 2 Acinetobacter spp. g 3 1 1 2 2 3 2 2 Burkholderia (Pseudomonas) 2 cepacia g Pseudomonas aeruginosa g 1 1 1 2 2 2 1 Stenotrophomonas (Xanthomonas) 3 3 2 2 1 maltophilia Pasteurella multocida 2 3 3 3 2 3 3 3 2 2 Vibrio cholerae 2 3 2 3 3 1 3 Enterococcus faecalis 2 3 3 2 2 3 2 2 3 2 2 2 2 2 3 Vancomycin-resistant Enterococcus Enterococcus faecalis 3 3 3 1 1 3 1 2 Enterococcus faecium 3 3 3 3 3 2 2 1 2 2 2 3 2 2 Vancomycin-resistant Enterococcus faecium 3 3 2 1 1 1 3 1 Staphylococcus aureus 2 2 2 2 3 2 3 2 2 2 3 3 2 2 2 2 2 2 2 2 2 2 3 Community-associated methicillin-resistant 2 2 2 2 2 1 2 1 1 Staphy lococcus aureus v Hospital-associated methicillinresistant Staphylococcus aureus w 3 3 3 3 3 3 1 1 2 2 2 3 2 3 1 Glycopeptide-intermediate susceptible Staphylococcus aureus 3 1 1 1 3 1 1 3 4
Table 2. Aminoglycosides, Macrolides, Quinolones, & Other Antibiotics (continued) Macrolides Quinolones r Other Antibiotics UTI Agents u Amikacin Gentamicin Streptomycin Tobramycin Azithromycin Clarithromycin Dirithromycin Erythromycin Ciprofloxacin Gemifloxacin Levofloxacin Moxifloxacin Chloramphenicol Clindamycin Colistin/Polymixin B Daptomycin s Fidoxamicin Linezolid Metronidazole Quinupristin-Dalfopristin Rifampin Telavancin Telithromycin Tetracyclines (eg, Doxycycline) t Tigecycline Trimethoprim-Sulfamethoxazole Vancomycin Fosfomycin Nitrofurantoin Norfloxacin Aerobes Anaerobes Bacilli Staphylococcus epidermidis 2 2 3 3 3 2 3 3 3 3 2 2 2 2 2 2 3 2 3 3 Methicillin-resistant Staphylococcus epidermidis 3 3 3 3 3 2 3 2 2 2 2 2 3 2 3 1 Streptococcus Group A (S. pyogenes) 2 2 2 2 3 2 2 3 2 2 2 2 2 2 2 3 2 3 2 2 Streptococcus Group B (S. agalactiae) 2 2 2 2 2 3 2 2 2 2 2 2 2 2 3 2 Streptococcus Group D (eg, S. bovis) 2 2 Streptococcus pneumoniae i 2 2 2 2 3 2 2 2 3 2 3 2 2 2 2 2 2 2 2 2 Penicillin-resistant Streptococcus pneumoniae j,k 3 3 3 3 3 1 1 1 2 3 2 2 3 2 1 2 1 Viridans streptococci 3 3 3 3 3 3 2 2 3 2 2 2 2 2 3 2 2 2 Actinomycetes Actinomyces israelii 3 3 3 3 3 3 2 Nocardia spp. 3 3 2 1 Bacillus anthracis l 3 2 1 3 3 1 3 Corynebacterium diphtheriae m 2 3 3 Corynebacterium jeikeium 2 3 2 2 1 Gardnerella vaginalis n 3 1 1 Listeria monocytogenes o 3 3 3 3 3 3 3 3 2 3 1 Bacteroides fragilis 3 3 3 3 1 2 3 3 2 Fusobacterium spp. 2 1 2 3 2 Mycoplasma Spiral Organisms Aminoglycosides Prevotella melaninogenica 2 2 3 2 2 2 1 3 2 Clostridium difficile p 3 1 2 1 3 2 3 2 1 Clostridium perfringens 2 3 3 3 3 3 3 2 2 2 2 2 3 Clostridium tetani 2 2 3 3 2 2 2 3 2 3 Peptostreptococcus spp. 3 3 3 3 3 2 2 2 2 3 2 2 3 Mycoplasma pneumoniae 1 1 1 1 1 2 2 2 2 2 2 Ureaplasma urealyticum 2 2 3 3 3 3 Borrelia burgdorferi q 2 2 3 1 Borrelia recurrentis (Lyme disease) 2 Leptospira spp. 2 Treponema pallidum 3 3 2 5
Table 3. Cephalosporins Generations 1st 2nd 3rd 4th Anti- MRSA Aerobes Aerobes Anaerobes Cefadroxil Cefazolin Cephalexin Cefaclor Coccobacilli Enterobacteriaceae Bacilli Moraxella catarrhalis 3 3 3 2 2 3 2 2 2 2 2 3 2 2 2 2 2 Neisseria gonorrhoeae a 3 3 3 3 3 3 2 2 3 2 2 1 2 Neisseria meningitidis 3 3 3 2 3 2 2 2 Chlamydia pneumoniae (TWAR) Chlamydia Chlamydia psittaci Chlamydia trachomatis Bordetella pertussis Brucella spp. b 3 2 2 3 2 2 2 2 2 Campylobacter jejuni Francisella tularensis Helicobacter pylori c Hemophilus ducreyi 2 2 2 3 2 2 1 Hemophilus influenzae d 2 2 2 2 2 1 1 1 1 2 2 1 1 2 2 Legionella pneumophila Citrobacter spp. e 3 3 2 2 2 2 1 2 Enterobacter spp. e,f 3 3 2 2 2 2 1 2 Escherichia coli f,g 1 1 1 2 2 2 2 2 2 1 2 2 2 1 1 2 2 Klebsiella spp.,g 2 2 2 3 2 2 2 2 2 1 2 2 2 1 1 2 2 Morganella morganii 3 3 3 1 2 2 1 1 1 2 Proteus mirabilis 2 2 2 2 2 2 2 2 2 1 2 2 2 1 1 1 2 Proteus vulgaris 3 3 3 1 3 2 2 1 1 1 2 Providencia stuartii 3 3 3 2 3 2 3 2 2 1 2 Salmonella spp. 3 3 3 1 2 1 1 2 Salmonella typhi 1 1 Serratia spp. 2 3 3 2 3 2 3 2 2 1 2 Shigella spp. 3 3 2 2 2 2 2 Acinetobacter spp. h 3 2 3 3 3 Burkholderia (Pseudomonas) cepacia h 3 3 Pseudomonas aeruginosa h 1 1 Stenotrophomonas (Xanthomonas) maltophilia 3 Pasteurella multocida 2 2 2 2 2 2 2 2 Vibrio cholerae Enterococcus faecalis Enterococcus Vancomycin-resistant Enterococcus faecalis Enterococcus faecium Vancomycin-resistant Enterococcus faecium Methicillin-susceptible Staphylococcus aureus 1 1 1 3 3 3 3 2 2 2 2 2 3 2 2 2 2 Methicillin-resistant Staphylococcus aureus 2 Glycopeptide-intermediate susceptible Staphylococcus aureus 1 Methicillin-susceptible Staphylococcus epidermidis 2 2 2 3 3 3 2 2 3 3 3 3 3 2 Methicillin-resistant Staphylococcus epidermidis 2 Streptococcus Group A (S. pyogenes) 2 2 2 2 3 3 2 2 2 2 2 2 2 3 2 2 2 2 Streptococcus Group B (S. agalactiae) 2 2 2 2 3 3 2 2 3 2 2 3 3 2 2 2 2 Streptococcus Group D (eg, S. bovis) 2 2 2 Streptococcus pneumoniae i 2 2 2 2 3 3 2 2 2 2 2 2 3 3 2 1 2 2 Penicillin-resistant Streptococcus pneumoniae j,k 2 x 2 x 2 2 Viridans streptococci 2 2 2 2 3 3 2 2 2 2 2 2 2 Actinomycetes Actinomyces israelii 3 3 2 Nocardia spp. 3 3 3 Bacillus anthracis l Corynebacterium diphtheriae m Corynebacterium jeikeium Gardnerella vaginalis n Listeria monocytogenes o Bacteroides fragilis 2 2 3 3 Fusobacterium spp. 2 2 2 3 2 2 Prevotella melaninogenica 2 2 2 3 2 2 Clostridium difficile p Clostridium perfringens 3 3 2 2 3 3 2 3 2 2 2 Clostridium tetani 3 3 3 3 3 Peptostreptococcus spp. 2 2 2 3 2 2 2 2 2 3 2 2 2 Myco plasma Mycoplasma pneumoniae Ureaplasma urealyticum Borrelia burgdorferi (Lyme disease) q 1 2 2 Spiral Borrelia recurrentis Organisms Leptospira spp. Treponema pallidum 2 2 Cefotetan Cefoxitin Cefprozil Cefuroxime Cefdinir Cefditoren Cefotaxime Cefpodoxime Ceftazidime Ceftibuten Ceftizoxime Ceftriaxone Cefepime Ceftaroline Other Bacilli (Nonenterobacteriaceae) 6
Notes to Chart a Resistance to penicillin, tetra cycline, and ciproflox acin may be as high as 21.5%, 29.2%, and 47.7%, respectively, according to a 2006 report; 50% of patients have Chlamydia trachomatis. b Use a combination: for example, doxycycline with gentamicin or rifampin or doxycycline with trimethoprim-sulfamethoxazole and chloramphenicol. c Combination therapy with high eradication rates includes omeprazole + clarithromycin + amoxicillin; or bismuth sub salicylate + metro nidazole + tetracycline. However, metro nidazole resistance has risen significantly. d Up to 30% of Haemophilus influenzae strains are capable of producing β-lactamases. e Citrobacter spp. and Enterobacter spp. may differ in susceptibility patterns. Consult individual test results for appropriate choice. f Carbapenemase-producing Enterobacteriaceae are increasing, and are endemic in certain geographic regions. Viable treatment options are limited and should be based on susceptibilities. Generally, colistin/polymixin B and tigecycline offer in vitro susceptibility, although clinical data are limited. Combination therapy is encouraged. g A significant number of strains are capable of producing extended-spectrum β-lactamases (ESBL). Consider this possibility according to antibiogram, patient s history, and local resistance patterns. In suspected or proven cases, use carbapenems or proper non β-lactam antibiotics based on susceptibility studies. h Combination therapy is suggested. i In 2005, the penicillin resistance rate in the United States was reported to be approximately 34%; 10% to 15% of isolates displayed high-level penicillin resistance (MIC [minimum inhibitory concentration] >1 mcg/ml). The Centers for Disease Control and Prevention Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group recommends MIC 4 mcg/ml for high-level resistance. The clinical significance of penicillin resistance in nonbacteremic patients is still uncertain when parenteral treatments are used. j PRSP (penicillin-resistant Streptococcus pneumoniae) being defined as nonsusceptible to penicillin (PCN [penicillin] MIC 2 mcg/ml). k Amoxicillin doses of 80 mg/kg/d may be effective against nonmeningeal RSP infections. l For updates, see www.fda.gov/oc/opacom/ hottopics/bioterrorism.html. m Membranous pharyngitis treated with antitoxin and IV erythromycin (antimicrobials used to decrease toxin production and bacterial spread). n New classification: bacteria are gram-variable. o Aminoglycosides (gentamicin) may be synergistic with β-lactams. p Gastroenteritis is treated with only oral formulations of vancomycin. Vancomycin is recommended as first-line therapy for patients with severe illness, while metronidazole is recommended for patients with mild to moderate disease. Fidaxomicin was non-inferior to oral vancomycin in treating CDI, but it was superior in preventing recurrences of non-nap1/ BI/027 strains. q Stage of disease determines choice of treatment. Consult specific references. r Resistance rates can vary greatly against P. aeruginosa, Acinetobacter spp., and the Enterobacteriaceae. Use as empiric therapy against these organisms should be based on local susceptibilities. s Despite its potent in vitro activity against Streptococcus pneumoniae, daptomycin is not indicated for the treatment of pneumonia, due to extensive binding to pulmonary surfactant resulting in clinical failure. t The specific tetracycline recommended varies. For methicillin-resistant Staphylococcus aureus, minocycline is most active among class. Consult specific references. u These agents are generally recommended for urinary tract infections (UTIs) only. Use of the 1 to 3 scale refers to activity for treatment of UTI. v Vancomycin is considered first-line when intravenous therapy is required. However, ceftaroline, daptomycin, linezolid, telavancin, and tigecycline may be suitable alternatives in specified patients. Tetracyclines, clindamycin, trimethoprim-sulfamethoxazole, macrolides, and linezolid are viable alternatives when oral therapy can be used. In the face of erythromycin resistance, clindamycin should be considered only if the isolate is D-test negative. w Vancomycin is considered first-line when IV therapy is required. Notably, in recent years vancomycin MICs have gradually increased for S. aureus and have included an increased occurrence of heteroresistance. Clinical reports have associated this loss of in vitro potency with vancomycin clinical failures in a number of patients. Alternative therapies such as ceftaroline, daptomycin, linezolid, telavancin, and tigecycline should be considered in the appropriate clinical setting. Consult specific references. x Effective choice for meningeal infections if the ceftriax one/cefotaxime MIC <0.5 mcg/ml. 7
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Int J Antimicrob Agents. 2005;26(5):380-388. Dr. Crandon reports no relevant conflicts of interest. Dr. Kuti has received research funding from and/or is on the speaker s bureau and/or advisory board for Astellas, BioMerieux USA, Forest, Merck, Ortho-McNeil, and Pfizer. Dr. Nicolau has received research funding from and/or is on the speaker s bureau and/or advisory board for AstraZeneca, Cerexa, Cubist, Forest, Johnson & Johnson, Merck, Ortho-McNeil, Pfizer, Rib-X, Tetraphase, and Vertex. Visit pharmacypracticenews.com Scan for commentary for a commentary on Implementing an Antimicrobial Stewardship Program by Steve Martin, PharmD, BCPS, FCCM, Chair of the Department of Pharmacy Practice at the University of Toledo College of Pharmacy 8