Evaluation of an optimized intermittent vancomycin dosing regimen in infants

Abstract

Background: Many standard intermittent dosing regimens for vancomycin in infants fail to achieve the therapeutic target at steady state. This study used population pharmacokinetic (popPK) modelling and simulation to determine an optimized vancomycin dosing regimen, and clinically evaluated this regimen in infants aged 0-90 days.

Methods: An optimized model-based dosing regimen to achieve an AUC24 of 400-650 mg/L·h was developed from a published vancomycin popPK model. The PTA of achieving the AUC24 target as well as a trough concentration of 10-20 mg/L (still commonly used in clinical practice as a surrogate for AUC24) was determined. This dosing regimen was implemented at The Royal Children's Hospital Melbourne, and evaluated over a 12 month period to determine the proportion of infants achieving the target AUC24 and trough concentration at steady state.

Results: Using the validated model, the simulated PTA of achieving the target AUC24 and trough concentration with the optimized dosing regimen was 68% and 56%, respectively. This dosing regimen was clinically evaluated in 24 infants who received 26 vancomycin courses (median postmenstrual age 40 weeks, range 25-53; median weight 3250 g, range 650-5930). In 23/26 (88%) courses, the target AUC24 was achieved, with 2/26 (8%) and 1/26 (4%) having subtherapeutic and supratherapeutic AUC24, respectively. The first trough concentration taken at steady state was between 10 and 20 mg/L in 21/26 (81%) courses. No nephrotoxicity or ototoxicity was observed.

Conclusions: Our optimized vancomycin dosing regimen for infants aged 0-90 days achieved the target AUC24 in 88% and should be considered for routine use.