The postantibiotic effect of imipenem: relationship with drug concentration, duration of exposure, and MIC

The postantibiotic effect (PAE) of imipenem against Escherichia coli was measured at a wide variety of drug concentrations and times of exposure. We observed that the area under the concentration-time curve of drug exposure (AUC), the product of time of exposure and concentration of drug, is a much better predictor of the duration of the PAE than either parameter alone. We also measured the PAE of imipenem against strains of gram-positive and gram-negative bacteria for which MICs varied widely. The E50, the AUC required to produce 50% of the maximum PAE, is correlated with the MIC and is independent of species. This may explain why the duration of the PAE differs for bacteria of the same species for which MICs are different.