Early Bayesian Dose Adjustment of Vancomycin in Children: a Randomized Controlled Trial

Methicillin-resistant staphylococcal infections are still a global burden. Area under the curve (AUC) of the serum concentrations versus time to minimum inhibitory concentration (MIC) ratio is the PK parameter that best predicts vancomycin efficacy. Vancomycin pharmacological target is narrow and difficult to achieve because of a wide interindividual variability, especially in children. The aim of this study was to assess if an early Bayesian dose adjustment of vancomycin would increase the rate of target attainment, at the 24th hour of treatment (H24). 

In this prospective randomized controlled trial, the routine care were compared with an early vancomycin plasma concentration monitoring (3h after treatment initiation) followed by an early Bayesian dose adjustment. The Bayesian estimation was made using a published population PK model that included age, body weight and serum creatinine as covariates. The primary study endpoint, analyzed with a Fisher’s exact test, was the proportion of patients achieving the pharmacological target of vancomycin AUC0-24/MIC ≥ 400 and ≤ 800 h at H24. 

Among the 99 patients aged 3 months to 17 years randomized in ICU, gastroenterology and immunohematology departments, 82 had analyzable data. All of them received continuous infusion of vancomycin. The proportion of patients who achieved the target at H24 was 85% in the Bayesian group versus 57% in the control group (p=0.007). In the Bayesian group, vancomycin dose was increased in 79% of patients, decreased in 8% and was not modified in 5 patients. There was no difference between the groups regarding iatrogenic events.
 
This study is the first to prospectively assess the contribution of early Bayesian dose adjustment of vancomycin. It increased the proportion of children achieving vancomycin pharmacological target at the 24th hour of treatment.

05 / EARLY BAYESIAN DOSE ADJUSTMENT OF VANCOMYCIN IN CHILDREN: A RANDOMIZED CONTROLLED TRIAL