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

• DOI: 10.1128/aac.01102-19
• Publication Date: 2019-10-03T11:25:30Z
• Authors: Romain Berthaud; Sihem Benaboud; Déborah Hirt; Mathieu Genuini; Mehdi Oualha; Martin Castelle; Coralie Briand; Solène Artru; Lorenzo Norsa; Olivia Boyer; Frantz Foissac; Naïm Bouazza; Jean-Marc Tréluyer
• Keywords: Therapeutic Drug Monitoring; Therapeutic index

Methicillin-resistant staphylococcal infections are a global burden. Area under the serum concentration-time curve to minimum inhibitory concentration (AUC/MIC) ratio is pharmacokinetic (PK) parameter that best predicts vancomycin efficacy. Its therapeutic range narrow, difficult achieve because of wide intersubject variability, especially in children, and not routinely targeted since AUC rarely available. We investigated if an early Bayesian dose adjustment would increase rate target attainment, first 24 hours treatment (H24), children.We conducted single-centre randomized controlled trial 4 pediatric departments Necker-Enfants Malades hospital (Paris, France). Patients aged 3 months 17 years for whom intravenous was started were eligible 1:1 ratio: routine care compared with drug monitoring (3h after initiation) followed by using previously published population-based PK model included age, bodyweight creatinine as covariates. The primary outcome proportion patients each group achieving at H24, defined AUC0-24/MIC≥400 AUC0-24 ≤800mg-h/L.Ninety-nine enrolled: 49 50 control group. Modified intention-to-treat analysis 82 patients: 85% achieved H24 versus 57% (p=0.007) no difference regarding iatrogenic events. Early increased children which may improve clinical outcomes methicillin-resistant infections.