Comparison of five β-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 (Cl-cr). Interventions. Serum concentration-time profiles were simulated for cefepime, ceftazidime, piperacillin, piperacillin-tazobactam, and imipenem at Cl-cr 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 (greater than or equal to 50%)). Measurements and Main Results. Cefepime 2 g every 12 hours (Cl-cr greater than or equal to 70 ml/min) and every 24 hours (Cl-cr less than or equal to 60 ml/min) achieved desirable T>MIC for all Enterobacteriaceae and S. aureus at every Cl-cr. Imipenem 0.5 g achieved desirable T>MIC for E. coli, K. pneumoniae, C. freundii, and S. aureus at every Cl-cr. However, imipenem T>MIC was less than 70% for the following regimens and organisms: S. marcescens 0.5 g every hours (Cl-cr greater than or equal to 90 ml/min), E. aerogenes 0.5 g every 6 hours (Cl-cr greater than or equal to 80 ml/min), E.. cloacae 0.5 g every 6 hours (Cl-cr greater than or equal to 100 ml/min), S. marcescens 0.5 g every 8 hours (Cl-cr 60-70 ml/min), E. cloacae 0.5 g every 8 hours (Cl-cr 60-70 ml/min), and E, aerogenes 0.5 g every 8 hours (Cl-cr 50-70 ml/min). Ceftazidime 2 g every 8 hours (Cl-cr 60-100 ml/min) and every 12 hours (Cl-cr 40-50 ml/min) achieved desirable T>MIC for E. coli, K. pneumoniae, S. marcescens, and S. aureus only At every dose and Cl-cr piperacillin-tazobactam achieved desirable T>MIC for S, aureus but not for any Enterobacteriaceae at Cl-cr > 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 Cl-cr. Conclusion. At every Cl-cr, 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 I! aeruginosa is a potential pathogen, empiric combination therapy should be considered.