Population Pharmacokinetic‐Based Meropenem Dosing in Critically and Non‐Critically Ill Patients with Mixed Gram‐Negative Bacterial Infections

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.