Comparison of five beta-lactam antibiotics against common nosocomial pathogens using the time above MIC at different creatinine clearances.

STUDY
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).
INTERVENTIONS: 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%).
MEASUREMENTS AND MAIN 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.
CONCLUSION: 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.