Model-informed precision dosing of vancomycin in children 3 months to 18 years of age using Australia-wide data

Vancomycin is used to treat serious gram-positive infections in children; however, effective dosing information for those aged 3 months to 18 years is limited. We aimed to determine an optimized dosing strategy for this age group. A population pharmacokinetic model was developed using data from The Royal Children's Hospital (RCH), Melbourne. Children aged 3 months to 18 years who received vancomycin were included. The model was externally validated with data from the Children's Hospital at Westmead (CHW), Sydney Children's Hospital (SCH), and Perth Children's Hospital (PCH). Simulations were performed to evaluate the standard dosing regimen and propose an optimized strategy, targeting an AUC_24-48 of 400-650 mg·h/L. An empirical loading dose was evaluated against the same therapeutic range for AUC_0-24 and AUC_24-48. The RCH data set included 3,687 vancomycin concentrations from 627 children. A two-compartment model with renal maturation best described the data. External validation (PCH 175, SCH 58, and CHW 170 concentrations) showed adequate predictive performance. The optimized dosing strategy achieved a target attainment of 73% versus 44% with the standard 15 mg/kg of body weight administered every 6 h. Improvement was most notable in patients <4 years, where the probability of target attainment (PTA) increased from 10.5%-48% to 66.1%-80% with the optimized regimen. A 25 mg/kg loading dose significantly increased the initial 24-h PTA to 57%, compared to 23% without a loading dose. We developed an optimized vancomycin dosing strategy that achieved the therapeutic target in 73% of children. This regimen requires prospective clinical validation.