Vancomycin continuous infusion in neonates: dosing optimisation and therapeutic drug monitoring

Objective Because pharmacokinetic data are limited, continuous infusions of vancomycin in neonates are administered using different dosing regimens. The aim of this work was to evaluate the results of vancomycin therapeutic drug monitoring (TDM) under three different dosing regimens and to optimise vancomycin therapy. Methods Vancomycin TDM concentrations were noted and compared prospectively in three hospitals. Population pharmacokinetic analysis was performed to optimise dosing using NONMEM software. Patient-tailored optimised dosing regimens were evaluated in a prospective study. Results Two hundred and seven serum vancomycin concentrations from 116 neonates were analysed. Only 48 neonates (41%) had serum vancomycin concentrations within the therapeutic range of 15-25 mg/l using a current dosing regimen. Concentrations ranged from 5.1 to 61.5 mg/l. Loading doses were required to decrease the risk of sub-therapeutic levels during early treatment. An optimised dosing regimen, taking into account birth weight, current weight, postnatal age and serum creatinine, was developed based on a one-compartment pharmacokinetic model. A prospective validation study in 58 neonates demonstrated a higher percentage of neonates (70.7%, n=41) reaching the therapeutic range and early dosage adaptation (6-12 h post-dose) using an optimised dosing regimen. Conclusions A patient-tailored optimised dosing regimen should be used routinely to individualise vancomycin continuous infusion therapy in neonates.