Identifying optimal dosing strategies for meropenem in the paediatric intensive care unit through modelling and simulation.

ABSTRACT:

Background

Meropenem, a β-lactam antibiotic commonly prescribed for severe infections, poses dosing challenges in critically ill patients due to highly variable pharmacokinetics.

Objectives

We sought to develop a population pharmacokinetic model of meropenem for critically ill paediatric and young adult patients.

Patients and methods

Paediatric intensive care unit patients receiving meropenem 20-40 mg/kg every 8 h as a 30 min infusion were prospectively followed for clinical data collection and scavenged opportunistic plasma sampling. Nonlinear mixed effects modelling was conducted using Monolix®. Monte Carlo simulations were performed to provide dosing recommendations against susceptible pathogens (MIC ≤ 2 mg/L).

Results

Data from 48 patients, aged 1 month to 30 years, with 296 samples, were described using a two-compartment model with first-order elimination. Allometric body weight scaling accounted for body size differences. Creatinine clearance and percentage of fluid balance were identified as covariates on clearance and central volume of distribution, respectively. A maturation function for renal clearance was included. Monte Carlo simulations suggested that for a target of 40% fT > MIC, the most effective dosing regimen is 20 mg/kg every 8 h with a 3 h infusion. If higher PD targets are considered, only continuous infusion regimens ensure target attainment against susceptible pathogens, ranging from 60 mg/kg/day to 120 mg/kg/day.

Conclusions

We successfully developed a population pharmacokinetic model of meropenem using real-world data from critically ill paediatric and young adult patients with an opportunistic sampling strategy and provided dosing recommendations based on the patients' renal function and fluid status.

SUBMITTER: Morales Junior R 

PROVIDER: S-EPMC11442002 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature