Objectives: In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. Methods: A ‘meta-model’ with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0–24 of 400 mgh/L at steady-state in at least 80% of neonates. Results: A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if ,35 weeks PMA and 15 mg/kg q8h if 35 weeks PMA) achieved the AUC0–24 target earlier than a standard ‘Blue Book’ dosage regimen in .89% of the treated patients. Conclusions: The results of a population meta-analysis of vancomycin data have been used to develop a new dosing regimen for neonatal use and to assist in the design of the model-based, multinational European trial, NeoVanc.

doi.org/10.1093/jac/dkz158, hdl.handle.net/1765/121233
Journal of Antimicrobial Chemotherapy
Department of Pediatric Surgery

Jacqz-Aigrain, E., Leroux, S, Thomson, A.H., Allegaert, K., Capparelli, E., Biran, V., … Zhao, W. (2019). Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants. Journal of Antimicrobial Chemotherapy, 74(8), 2128–2138. doi:10.1093/jac/dkz158