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

Authors :
Morales Junior R
Mizuno T
Paice KM
Pavia KE
Hambrick HR
Tang P
Jones R
Gibson A
Stoneman E
Curry C
Kaplan J
Tang Girdwood S
Source :
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2024 Oct 01; Vol. 79 (10), pp. 2668-2677.
Publication Year :
2024

Abstract

Background: Meropenem, a β-lactam antibiotic commonly prescribed for severe infections, poses dosing challenges in critically ill patients due to highly variable pharmacokinetics.<br />Objectives: We sought to develop a population pharmacokinetic model of meropenem for critically ill paediatric and young adult patients.<br />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).<br />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.<br />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.<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Details

Language :
English
ISSN :
1460-2091
Volume :
79
Issue :
10
Database :
MEDLINE
Journal :
The Journal of antimicrobial chemotherapy
Publication Type :
Academic Journal
Accession number :
39092928
Full Text :
https://doi.org/10.1093/jac/dkae274