Comparative in vitro pharmacodynamics of imipenem and meropenem against ATCC strains of Escherichia coli, Staphylococcus aureus and Bacteroides fragilis

We evaluated the pharmacodynamics of imipenem and meropenem, utilizing time-kill studies over a concentration/MIC (C/MIC) range of 0.0625-1024 for E. coli ATCC 35218 (EC) and S. aureus ATCC 29213 (SA) and from 0.125-512 for B. fragilis ATCC 25285 (BF). Area under the time-kill curves were converted to percent response (%R). AUCs were calculated from drug concentrations corrected for degradation and %R vs. C/MIC and AUC/MIC were fit to a sigmoidal Emax model. Emax was similar for both agents for all organisms. Meropenem was 4x more potent than imipenem against EC based on the MIC and required 7 and 13.5-fold lower AUCs to achieve E50 and E90, (50% and 90% of the maximal response, respectively) respectively, whereas imipenem was 8x more potent than meropenem against SA based on the MIC and required 8 and 13-fold lower AUCs to achieve E50 and E90, respectively. The C/MIC and AUC/MIC to achieve E50 and E90 with imipenem were 2- and fourfold higher, respectively than meropenem against EC. There was less than a twofold difference in C/MICs and AUC/MIC between imipenem and meropenem for both E50 and E90 against SA. Against BF, concentrations and AUCs at E50 were similar for both agents; however, imipenem required 4 to 6-fold higher concentrations and AUC to achieve E90. Although there are differences in the potency of these agents as assessed by the MIC or AUC vs. response, when normalized by the MIC and corrected for drug degradation, these agents displayed similar pharmacodynamic parameter-response relationships.