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Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants.

Jacqz-Aigrain, E; Leroux, S; Thomson, AH; Allegaert, K; Capparelli, EV; Biran, V; Simon, N; Meibohm, B; Lo, Y-L; Marques, R; et al. Jacqz-Aigrain, E; Leroux, S; Thomson, AH; Allegaert, K; Capparelli, EV; Biran, V; Simon, N; Meibohm, B; Lo, Y-L; Marques, R; Peris, J-E; Lutsar, I; Saito, J; Nakamura, H; van den Anker, JN; Sharland, M; Zhao, W (2019) Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants. J Antimicrob Chemother, 74 (8). pp. 2128-2138. ISSN 1460-2091 https://doi.org/10.1093/jac/dkz158
SGUL Authors: Sharland, Michael Roy

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Abstract

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 mg·h/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.

Item Type: Article
Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Antimicrobial Chemotherapy following peer review. The version of record Evelyne Jacqz-Aigrain, Stéphanie Leroux, Alison H Thomson, Karel Allegaert, Edmund V Capparelli, Valérie Biran, Nicolas Simon, Bernd Meibohm, Yoke-Lin Lo, Remedios Marques, José-Esteban Peris, Irja Lutsar, Jumpei Saito, Hidefumi Nakamura, Johannes N van den Anker, Mike Sharland, Wei Zhao, 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, Volume 74, Issue 8, August 2019, Pages 2128–2138 is available online at: https://doi.org/10.1093/jac/dkz158
Keywords: 1115 Pharmacology And Pharmaceutical Sciences, 0605 Microbiology, 1108 Medical Microbiology, Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Antimicrob Chemother
ISSN: 1460-2091
Language: eng
Dates:
DateEvent
August 2019Published
2 May 2019Published Online
16 March 2019Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
602041Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
2017ZX09304029-002China National Science and Technology Major ProjectsUNSPECIFIED
PubMed ID: 31049551
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110928
Publisher's version: https://doi.org/10.1093/jac/dkz158

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