Evaluatie van een nieuwe Nederlandse vancomycine- doseerrichtlijn en populatiefarmacokinetiek van vancomycine bij preterme en a terme neonaten

Evaluation of a new Dutch guideline for vancomycin dosing and population pharmacokinetics of vancomycin for preterm and term neonates OBJECTIVE In May 2015 the Dutch pediatric formulary (Kinderformula- rium) introduced a new guideline for dosing of vancomycin in neonates. The primary aim of this study was to validate this guideline by assessing the percentage of therapeutic initial trough serum concentrations in a cohort of (pre)term neonates. The secondary aim of this study was to describe the population pharmacokinetics (PPK) of vancomycin in (pre)term neonates. METHODS In this prospective study, (pre)term neonates were included when admitted to the Neonatology department of the Academic Medical Center. Amsterdam from May 2015 to June 2017. Vancomycin dosing was performed according to the new guideline. Serum concentrations were measured prior to the administration of the fifth dose. Trough levels in the range of 10 to 15 mg/L were considered therapeutic. PPK parameters were estimated by nonlinear mixed-effects modeling. RESULTS Forty patients were included for the primary aim and 42 patients for the secondary aim of this study. The main category of patients were premature neonates with a postnatal age of 1 to 4 weeks (n - 27, 68%). In this group 15 patients (56%) had a subtherapeutic vancomycin serum level, while therapeutic and supratherapeutic levels were found in 7 (26%) and 5119%) of the patients, respectively. The PPK were best described by an allometric, one-compartment model. Inter-patient variability in clearance could be explained by variation in renal function and postmenstrual age. CONCLUSION The new dosing guideline does not produce therapeutic vancomycin concentrations in the majority of premature neonates from 1 to 4 weeks old. Further research is needed to optimize dosing of vancomycin in neonates.