Meropenem Disposition in Neonatal and Pediatric Extracorporeal Membrane Oxygenation and Continuous Renal Replacement...

Area of Science:

• Pharmacology
• Critical Care Medicine
• Pediatric Infectious Diseases

Background:

• Meropenem is a critical antibiotic for serious infections in neonates and children.
• Extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) are complex life support modalities used in critically ill pediatric patients.
• Understanding drug pharmacokinetics (PK) during these therapies is crucial for effective treatment.

Purpose of the Study:

• To evaluate the impact of ECMO on meropenem PK in pediatric patients.
• To assess the influence of CRRT on meropenem PK.
• To propose optimized meropenem dosing strategies for patients on ECMO and/or CRRT.

Main Methods:

• Population PK analysis using NONMEM V7.3.0 on 152 meropenem plasma concentrations from 45 pediatric patients.
• Inclusion of ECMO and CRRT status as covariates in the PK model.
• Monte Carlo simulations to determine probability of target achievement (PTA) for various dosing regimens and minimum inhibitory concentrations (MICs).

Main Results:

• Body weight was a significant covariate for meropenem volume of distribution (Vd) and clearance (CL).
• CRRT was associated with a two-fold increase in Vd; ECMO did not significantly impact meropenem PK.
• Standard dosing achieved acceptable PTA for 40% fT > MIC (meropenem free time above MIC) at MIC ≤ 4 mg/L.

Conclusions:

• ECMO does not alter meropenem PK in neonates and children.
• CRRT significantly increases meropenem Vd, requiring dose adjustments.
• Current meropenem dosing may be insufficient for achieving 100% fT > MIC, especially with CRRT, necessitating individualized dosing recommendations.