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 concentra tion (T>MIC) for five parenteral beta-lactam antibiotics against common nos ocomial bacterial pathogens at different creatinine clearances (Cl-cr). Interventions. Serum concentration-time profiles were simulated for cefepim e, ceftazidime, piperacillin, piperacillin-tazobactam, and imipenem at Cl-c r ranging from 120-30 ml/minute. The MIC data for 90% of organisms (MIC90) were collected for Escherichia coli, Klebsiella pneumoniae, Serratia marces cens, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, P seudomonas aeruginosa, and oxacillin-susceptible Staphylococcus aureus, and a weighted geometric mean MIC90 was calculated. The T>MIC was calculated a s percentage of the dosing interval in which free concentrations exceeded t he 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 t han 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. aureu s at every Cl-cr. Imipenem 0.5 g achieved desirable T>MIC for E. coli, K. p neumoniae, C. freundii, and S. aureus at every Cl-cr. However, imipenem T>M IC was less than 70% for the following regimens and organisms: S. marcescen s 0.5 g every hours (Cl-cr greater than or equal to 90 ml/min), E. aerogene s 0.5 g every 6 hours (Cl-cr greater than or equal to 80 ml/min), E.. cloac ae 0.5 g every 6 hours (Cl-cr greater than or equal to 100 ml/min), S. marc escens 0.5 g every 8 hours (Cl-cr 60-70 ml/min), E. cloacae 0.5 g every 8 h ours (Cl-cr 60-70 ml/min), and E, aerogenes 0.5 g every 8 hours (Cl-cr 50-7 0 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. pneumo niae, S. marcescens, and S. aureus only At every dose and Cl-cr piperacilli n-tazobactam achieved desirable T>MIC for S, aureus but not for any Enterob acteriaceae 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 7 0% or above for P. aeruginosa at any Cl-cr. Conclusion. At every Cl-cr, cefepime achieved a desirable T>MIC for more no socomial pathogens than any other beta-lactam evaluated. Based on pharmacod ynamic data, cefepime is an appropriate empiric choice for treatment of nos ocomial infections. However, when I! aeruginosa is a potential pathogen, em piric combination therapy should be considered.