Optimizing the Meropenem Dosing Regimen in Neonates: A Dual-Centre Cohort Study

Area of Science:

• Pharmacology
• Neonatal Medicine
• Infectious Diseases

Background:

• Meropenem is a critical antibiotic for treating serious infections in neonates.
• Optimizing meropenem dosing is essential for effective treatment and minimizing resistance.
• Neonatal pharmacokinetics differ significantly from older populations, necessitating specific dosing strategies.

Purpose of the Study:

• To characterize meropenem pharmacokinetics in neonates.
• To identify optimal meropenem dosing regimens for achieving therapeutic targets against common pathogens.
• To evaluate the efficacy of traditional versus novel dosing strategies.

Main Methods:

• Retrospective analysis of meropenem plasma concentrations in 114 neonates.
• Development and external validation of a population pharmacokinetic model.
• Monte Carlo simulations to assess target attainment and cumulative fraction of response (CFR) for different regimens.

Main Results:

• Body weight and congenital heart disease were significant covariates influencing meropenem clearance and volume of distribution.
• Traditional simple/prolonged-infusion (TSPI) regimens often required high doses for aggressive targets.
• Optimized two-step administration therapy (OTAT) regimens, particularly 5+15 mg/kg, demonstrated high predicted CFR (≥90%) for common pathogens.

Conclusions:

• Neonatal meropenem pharmacokinetics are significantly influenced by body weight and congenital heart disease.
• The 5+15 mg/kg OTAT regimen offers a model-informed alternative to dose escalation.
• Prospective clinical studies are recommended to validate this optimized dosing strategy.