Comparison of Short Versus Prolonged Infusion of Standard Dose of Meropenem Against Carbapenemase-Producing Klebsiella pneumoniae Isolates in Different Patient Groups: A Pharmacokinetic-Pharmacodynamic Approach: Pharmacokinetics, Pharmacodynamics and Drug Transport and Metabolism

Dose optimization is required to increase carbapenem's efficacy against carbapenemase-producing isolates. Four clinical Klebsiella pneumoniae isolates were used: one susceptible to meropenem with minimum inhibitory concentration (MIC) 0.031 mg/L and 3 verona integron-borne metallo bete-lactamase-1-producing isolates with MICs 8, 16, and 128 mg/L. The human pharmacokinetics of short (0.5-h) and prolonged (3-h) infusion regimens of 1 g meropenem every 8 h were simulated in an in vitro pharmacokinetic-pharmacodynamic model. Time-kill curves were constructed for each isolate and dosing regimen, and the %T > MIC associated with maximal bactericidal activity was estimated. The percentage of pharmacodynamic target attainment for isolates with different MICs was calculated for 350 ICU, surgical, and internal medicine patients. The isolates with MIC less than or equal to 8 mg/L were killed with both dosing regimens. The %T > MIC corresponding to maximal bactericidal activity was 40%. The percentages of target attainment were >90%, 61%-83%, 23%-33%, and 90%, 98%-99%, 55%-79%, and