Population Pharmacokinetic-Based Meropenem Dosing in Critically and Non-Critically Ill Patients with Mixed...

This study aimed to describe the population pharmacokinetic (PK) of meropenem in patients with mixed Gram-negative bacterial infections, and further to develop optimal dosing regimens for both non-critically ill and critically ill patients by combining different pharmacokinetic/pharmacodynamic (PK/PD) targets. Based on retrospectively collected data from patients who underwent therapeutic drug monitoring (TDM) for meropenem, including demographic characteristics, medication records, and laboratory results, a population PK model was developed via nonlinear mixed-effects modeling. Dosing regimens were subsequently evaluated and provided through Monte Carlo simulation. The population PK analysis of meropenem included 86 steady-state concentrations from 39 adult patients. The data were modeled using a one-compartment model. The final model yielded a population typical value for clearance (CL) of 6.10 L/h. Our study showed that estimated glomerular filtration rate (eGFR) significantly affected the PK of meropenem. Monte Carlo simulation results demonstrated that a regimen of 0.5-h infusion every 8 h was sufficient to achieve the conventional target of 40% ƒT > MIC in most scenarios. In contrast, achieving the more aggressive target of 100% ƒT > MIC required a regimen of every 6 h; for MIC ≥ 4 mg/L pathogens, this needed to be coupled with an extended infusion time of 3 h. Furthermore, continuous infusion regimens demonstrated a distinct advantage in critically ill patients. This study successfully established a population PK model of meropenem and provided a reference for dosing adjustment based on clinical severity and renal function.