Vancomycin dosing in neonates: enhancing outcomes using population pharmacokinetics and simulation.

Introduction: Optimizing vancomycin dosing in neonates is a critical yet complex goal. Traditional trough concentration-based dosing strategies correlate poorly with therapeutic efficacy and often fail to account for the significant renal function variability and drug clearance in neonates. The 24-hour area under the concentration-time curve to minimum inhibitory concentration (AUC Objective: To develop optimized vancomycin dosing regimens for neonates that achieve an 80% probability of target attainment (PTA) for an AUC Methods: Real-world data from three international centers (Belgium, New Zealand, USA), including 610 individuals and 2399 vancomycin concentrations, were used to externally evaluate a previously published PopPK model (NONMEM Results: Simulations showed that PMA and SCr were key covariates that significantly improved PTA, particularly in preterm neonates. Preterm neonates achieved PTAs of 80% with daily doses of 30 or 40 mg/kg/day, while term neonates required 15 mg/kg every 8 hours or 20 mg/kg every 12 hours. The simulations demonstrated that these optimized dosing strategies achieved an 80% PTA for AUC Conclusion: Incorporating developmental factors like PMA and SCr into vancomycin dosing strategies achieved robust and clinically relevant outcomes. The optimized regimens achieved an 80% PTA for the AUC