Vancomycin in Pediatric Patients with Cystic Fibrosis: Dose Optimization Using Population Pharmacokinetic Approach.

Abstract

An increase in Staphylococcus aureus infections has been reported in pediatric patients with cystic fibrosis (CF) over the last few years. This pathogen is commonly treated with vancomycin, an antibiotic for which therapeutic drug monitoring (TDM) is recommended. Updated guidelines were recently published regarding new targets of exposure for the TDM of vancomycin through a Bayesian approach, using population pharmacokinetic (popPK) models. This study aims to assess the predictive performance of vancomycin popPK models in pediatric patients with CF and to recommend optimal initial dosing regimens based on simulations. Patient data were collected from two centers in Canada, and a literature review was conducted to identify all published vancomycin popPK models for pediatric CF patients. External evaluation and simulations were performed according to patient and occasion of treatment. A total of 53 vancomycin concentrations were collected from six pediatric CF patients. Only two popPK models of vancomycin for pediatric CF patients were identified through the literature review. The external evaluation results for both centers combined revealed a population bias of 28.1% and an imprecision of 33.7%. A re-estimation of parameters was performed to improve predictive performance. The optimal initial dosing regimen was 15 mg/kg/dose administered every 6 hours according to the per occasion remodel. The predictive performance and identified optimal initial dosing regimens associated with the model were different depending on the data used, showing external evaluation's importance before implementing a model in clinical practice.