Comparison of five beta-lactam antibiotics against common nosocomial pathogens using the time above MIC at different creatinine clearances.
OBJECTIVE
To compare the time above the minimum inhibitory concentration (T>MIC) for five parenteral beta-lactam antibiotics against common nosocomial bacterial pathogens at different creatinine clearances (Clcr).


METHODS
Serum concentration-time profiles were simulated for cefepime, ceftazidime, piperacillin, piperacillin-tazobactam, and imipenem at Clcr ranging from 120-30 ml/minute. The MIC data for 90% of organisms (MIC90) were collected for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Pseudomonas aeruginosa, and oxacillin-susceptible Staphylococcus aureus, and a weighted geometric mean MIC90 was calculated. The T>MIC was calculated as percentage of the dosing interval in which free concentrations exceeded the weighted geometric mean MIC90. A T>MIC of 70% or greater was considered desirable for all organisms except S. aureus (> or = 50%).


RESULTS
Cefepime 2 g every 12 hours (Clcr > or = 70 ml/min) and every 24 hours (Clcr < or = 60 ml/min) achieved desirable T>MIC for all Enterobacteriaceae and S. aureus at every Clcr. Imipenem 0.5 g achieved desirable T>MIC for E. coli, K. pneumoniae, C. freundii, and S. aureus at every Clcr. However, imipenem T>MIC was less than 70% for the following regimens and organisms: S. marcescens 0.5 g every 6 hours (Clcr > or = 90 ml/min), E. aerogenes 0.5 g every 6 hours (Clcr > or = 80 ml/min), E. cloacae 0.5 g every 6 hours (Clcr > or = 100 ml/min), S. marcescens 0.5 g every 8 hours (Clcr 60-70 ml/min), E. cloacae 0.5 g every 8 hours (Clcr 60-70 ml/min), and E. aerogenes 0.5 g every 8 hours (Clcr 50-70 ml/min). Ceftazidime 2 g every 8 hours (Clcr 60-100 ml/min) and every 12 hours (Clcr 40-50 ml/min) achieved desirable T>MIC for E. coli, K. pneumoniae, S. marcescens, and S. aureus only. At every dose and Clcr, piperacillintazobactam achieved desirable T>MIC for S. aureus but not for any Enterobacteriaceae at Clcr > 50 ml/minute. Piperacillin did not achieve desirable T>MIC for any organism, and none of the beta-lactams attained a T>MIC of 70% or above for P. aeruginosa at any Clcr.


CONCLUSIONS
At every Clcr, cefepime achieved a desirable T>MIC for more nosocomial pathogens than any other beta-lactam evaluated. Based on pharmacodynamic data, cefepime is an appropriate empiric choice for treatment of nosocomial infections. However, when P. aeruginosa is a potential pathogen, empiric combination therapy should be considered.
Kays
M B
MB
Department of Pharmacy Practice, School of Pharmacy and Pharmacal Sciences, Purdue University, Indianapolis, Indiana 46202-2879, USA.
D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D000077723:Cefepime; D002442:Ceftazidime / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D006801:Humans; D015378:Imipenem / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D010878:Piperacillin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000078142:Tazobactam; D013997:Time Factors
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D015378:Imipenem; D000077723:Cefepime; D010397:Penicillanic Acid; D002442:Ceftazidime; D003404:Creatinine; D000078142:Tazobactam; D010878:Piperacillin