Population pharmacokinetic study of meropenem in patients with severe infections and Monte Carlo simulation of the efficacy under different dosing regimens.

BACKGROUND

Meropenem is a first-line carbapenem for severe Gram-negative infections, but its pharmacokinetics varies markedly in patients with severe infections. Individualized dosing guided by population pharmacokinetic (PPK) modeling is essential to optimize efficacy and limit resistance.

METHODS

We performed a retrospective PPK study in patients with severe infections using nonlinear mixed-effects modeling. Monte Carlo simulations were conducted to determine probability of target attainment (PTA) and cumulative fraction of response (CFR) across regimens.

RESULTS

A one-compartment model best described the data, with creatinine clearance (CLCR) as a significant covariate on drug clearance. Good model fit and predictive performance were confirmed. PTA/CFR decreased with higher CLCR or higher minimum inhibitory concentration (MIC).

CONCLUSION

Renal function and pathogen MIC strongly drive meropenem exposure. Frequent dosing is superior to increasing single dose to optimize PTA/CFR in patients with rapid clearance or resistant infections. Our model supports CLCR-based individualized dosing for severe infections.