Background:Vancomycin is commonly used for nosocomial bacterial pathogens causing late-onset septicemia in preterm infants. We prospectively collected pharmacokinetic data aiming to describe PK and determine covariates contributing to the variability in neonatal vancomycin pharmacokinetics. Further, we aimed to use the model to compare AUC24h,SS/MIC of several intermittent and continuous dosing regimens. Methods: Newborns receiving vancomycin for suspected or confirmed late-onset sepsis were included. Peak and trough concentrations for intermittent vancomycin dosing and steady-state concentrations for continuous vancomycin dosing were measured. NONMEM 7.3 was used for population pharmacokinetic analysis. Monte Carlo simulations were performed to compare dosing schemes. Results: Data from 54 infants were used for model development and from 34 infants for the model evaluation of a median (range) 29 (23.4-41.9) weeks and 28 (23.4-41.7) weeks corrected gestational age (GA), respectively. The final model was a 1-compartment model. Weight and postmenstrual age were included a priori; and after that no additional covariate significantly improved the model fit. Final model parameter estimates (mean (standard error)): CL 5.7 (0.3) L/h/70kg, V 39.3 (3.7) L/70kg. Visual predictive check of the evaluation dataset confirmed the model can predict external data. Simulations using MIC of 1 mg/Lshowed that for neonates with GA ≤25 weeks and postnatal age ≤2 weeks AUC24h,SS/MIC was lower with the intermittent regimen (median 482 versus 663). Conclusions:A population PK model for continuous and intermittent vancomycin administration in infants was developed. Continuous administration might be favourable for treating infections caused by resistant microorganisms in very young and immature infants.

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