Cefepime population pharmacokinetics and dosing regimen optimization in critically ill children with different renal function

Objective: Cefepime is commonly used in pediatric intensive care units, where unpredictable variations in the patients' pharmacokinetic (PK) variables may require drug dose adjustments. The objectives of the present study were to build a population PK model for cefepime in critically ill children and to optimize individual initial dosing regimens. Methods: Children (aged from 1 month to 18 years; body weight >3 kg) receiving cefepime were included. Cefepime total plasma concentrations were measured using high performance liquid chromatography. Data were modelled using nonlinear, mixed-effect modeling software, and Monte Carlo simulations were performed with a 13K target of 100% fT (> MIC). Results: Fifty-nine patients (median (range) age: 13.5 months (1.1 months to 17.6 years)) and 129 cefepime concentration measurements were included. The cefepime concentration data were best fitted by a one-compartment model. The selected covariates were body weight with allometric scaling and estimated glomerular filtration rate on clearance. Mean population values for clearance and volume were 1.21 L/h and 4.8 L, respectively. According to the simulations, a regimen of 100 mg/kg/d q12 h over 30 min or 100 mg/kg/d as a continuous infusion was more likely to achieve the PK target in patients with renal failure and in patients with normal or augmented renal clearance, respectively. Discussion: Appropriate cefepime dosing regimens should take renal function into account. Continuous infusions are required in critically ill children with normal or augmented renal clearance, while intermittent infusions are adequate for children with acute renal failure. Close therapeutic drug monitoring is mandatory, given cefepime's narrow therapeutic window. (C) 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Automated summary

The study aimed to build a population pharmacokinetic (PK) model for cefepime in critically ill children and optimize individual initial dosing regimens. The results showed that body weight and estimated glomerular filtration rate were associated with drug clearance. According to the simulations, continuous intravenous infusion of cefepime was more likely to achieve the PK target in patients with renal failure, while intermittent intravenous infusion was adequate for patients with normal or augmented renal clearance. Close therapeutic drug monitoring is necessary for cefepime treatment.