Population pharmacokinetics and dosing simulations of meropenem in septic critically ill patients with complicated intraabdominal infection or pneumonia

Objectives: Meropenem pharmacokinetics (PK) may be altered in septic critically ill patients with complicated intra-abdominal infections (cIAI) and pneumonia. We aimed to evaluate the covariates affecting meropenem PK and the performance of different dosing regimens to optimize the PK/pharmacodynamic target. Methods: Population PK analysis was performed using non-linear mixed-effects modeling. The final model was validated and used to simulate meropenem exposure to assess the probability of attaining the 100 %& fnof;T->MIC target. Results: Forty-six and 14 patients were respectively enrolled for PK analysis and external validation. A one-compartment linear model adequately described the data of 226 concentrations. The typical clearance (CL) and volume of distribution (Vd) were 9.69 L/h and 27.4 L, respectively. Septic shock from cIAI (cIASS) and actual body weight were significant covariates for meropenem Vd in addition to the influential covariates of creatinine clearance (CLCR-CG) and augmented renal clearance for CL. External validation showed the robustness and accuracy of this model. Simulation results proposed continuous infusion (CI) dosing regimens of meropenem against pathogens with MICs >= 2 mg/L in patients with cIASS and CLCR-CG >= 60 mL/min. Conclusions: For the patients with cIASS and CLCR-CG >= 60 mL/min, CI meropenem is proposed for treatment of less sensitive pathogens with MICs >= 2 mg/L. (c) 2024 American Pharmacists Association. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.