External validation of the population pharmacokinetic model of meropenem in patients undergoing neonatal extracorporeal membrane oxygenation and continuous renal replacement therapy

Rational meropenem dosing during neonatal extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy is hindered by a lack of validated pharmacokinetic models for this complex clinical scenario. This study externally validated a previously developed meropenem population pharmacokinetic model using 100 plasma concentrations from 28 neonates undergoing ECMO and continuous renal replacement therapy, with modeling performed in NONMEM and evaluated through prediction error and NPDE diagnostics. Population-based predictions alone showed minimal bias but limited precision, though incorporating just one prior measured concentration through Bayesian forecasting markedly improved predictive accuracy. The findings indicate this meropenem model is not suitable for a priori dosing in neonatal ECMO patients but performs well for Bayesian, therapeutic-drug-monitoring-guided dosing once at least one concentration is available.