Introduction: Vancomycin dosing tailored for newborns is challenging due to the significant influence of maturation and organ function on pharmacokinetics. Population pharmacokinetic (popPK) models can be used to improve target attainment in neonates. Objectives: The primary objective was to derive and evaluate a popPK model of intravenous vancomycin for neonates. Second, the predictive performance of this popPK model was compared with published popPK models. Methods: This is a retrospective cohort study of neonates admitted to the neonatal intensive care unit receiving intravenous vancomycin. A popPK model was derived with 70% of the dataset using a nonlinear mixed effects modeling method. The predictive performance of the current popPK model was validated and compared with 22 published popPK models using the remaining 30% of the dataset. Monte Carlo simulations (MCS) were performed to derive optimal dosing regimens to treat neonatal sepsis caused by coagulase‐negative staphylococci (CoNS). Results: Among 655 vancomycin courses from 448 neonates, 78% of vancomycin trough concentrations were outside target range (10–15 mg/L) for central nervous system infections and 43% were outside target range (5–12 mg/L) for other infections using the institution's vancomycin dosing. A one‐compartment model best described the observed data with a mean clearance of 0.11 ± 0.03 L/kg/h and volume of distribution (V) of 1.02 ± 0.08 L/kg. Body weight (WT), postmenstrual age (PMA), and serum creatinine (SCr) were significant covariates associated with clearance ( p < 0.001) and body WT was a significant covariate associated with V ( p = 0.009). Our study's popPK model has similar or better accuracy and precision than other published models. MCS‐derived vancomycin doses from the validated model achieved >90% target attainment for a steady state through target range of 10–15 mg/L in the majority of PMA and SCr categories (78%) to treat CoNS sepsis. Conclusion: A vancomycin dosing guideline derived from a validated popPK model in neonates with CoNS sepsis is recommended to improve target attainment.

Vancomycin is a common antibiotic used to treat hemodialysis (HD) or hemodiafiltration (HDF)-related infections in pediatric patients, but optimal dosing remains unknown. This is the first observational study to characterize the pharmacokinetics and evaluate dosing of vancomycin in this population. Eligible patients received IV vancomycin 10 mg/kg per dose postdialysis followed by a series of serum vancomycin concentrations collected before, immediately after, 1 hour after, and 4 hours after dialysis. The pharmacokinetic parameters were estimated using 1- and 2-compartment models and a nonlinear least-squares algorithm. Among 42 vancomycin courses in 16 patients, 1 compartment model had the best fit for observed data. The net drug removal was 43 ± 13% (39% for HD and 50% for HDF) from an average 3-hour HD/HDF session. The mean elimination constant was 0.28 h−1 (standard deviation [SD], 0.11 h−1) during the intradialytic period compared with 0.0049 h−1 (SD, 0.004 h−1) when off dialysis. The mean volume of distribution was 0.65 (SD, 0.19) L/kg. Duration of dialysis session and mode of dialysis (HD vs. HDF) were significant predictors of vancomycin pharmacokinetic parameters. Half-life was shorter for HDF compared with HD (2.1 vs. 3.5 hours). Based on the simulations, an initial vancomycin dose of 10 mg/kg per dose and redosing postdialysis was optimal to achieve a vancomycin concentration range of 5 to 12 mg/L at 4 hours postdialysis and 24-hour area under the curve over minimum inhibitory concentration of ≥400 hours. Therapeutic drug monitoring is necessary to account for residual variability in vancomycin elimination in pediatric patients receiving HD/HDF.

Background/Objectives: Vancomycin dosing in neonates is challenging due to high pharmacokinetic variability and immature renal function. This study evaluated current therapeutic drug monitoring (TDM) practices, the association between vancomycin concentration and clinical outcomes, and the predictive performance of a locally developed population pharmacokinetic (popPK) model compared to the published models. Methods: This was a retrospective cohort study of neonates admitted to a tertiary neonatal intensive care unit (NICU). We assessed the persistent positive culture, infection recurrence, mortality and acute kidney injury (AKI) stratified by initial vancomycin trough concentrations (15 mg/L). The locally developed popPK model was externally validated and compared with 32 other published neonatal vancomycin popPK models (with a total of 33 models evaluated). Results: A total of 366 neonates were included (mean postmenstrual age of 28.9 ± 3.81 weeks; 191 received at least 5 days of vancomycin). Only 28% of neonates achieved initial vancomycin trough concentrations within the 10–15 mg/L using standard vancomycin dosing. Higher vancomycin trough concentrations (>15 mg/L) were not associated with improved efficacy but were significantly associated with a higher incidence of AKI. The locally derived popPK model demonstrated superior predictive accuracy, meeting all predefined performance criteria, whereas none of the 32 other published models met all the criteria. Conclusions: Current vancomycin dosing strategies often result in suboptimal exposure and increased nephrotoxicity without added efficacy. Model-informed precision dosing using the locally developed popPK model may offer a safer, more effective approach for neonatal vancomycin therapy.