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Development and external evaluation of a population pharmacokinetic model for continuous and intermittent administration of vancomycin in neonates and infants using prospectively collected data

Germovsek, E; Osborne, L; Gunaratnam, F; Lounis, SA; Busquets, FB; Standing, JF; Sinha, AK; (2019) Development and external evaluation of a population pharmacokinetic model for continuous and intermittent administration of vancomycin in neonates and infants using prospectively collected data. Journal of Antimicrobial Chemotherapy , 74 (4) pp. 1003-1011. 10.1093/jac/dky525. Green open access

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Abstract

BACKGROUND: Vancomycin is commonly used for nosocomial bacterial pathogens causing late-onset septicaemia in preterm infants. We prospectively collected pharmacokinetic data aiming to describe pharmacokinetics and determine covariates contributing to the variability in neonatal vancomycin pharmacokinetics. Further, we aimed to use the model to compare the ratio of AUC24 at steady-state to the MIC (AUC24,ss/MIC) of several intermittent and continuous dosing regimens. METHODS: Newborns receiving vancomycin for suspected or confirmed late-onset sepsis were included. Peak and trough concentrations for intermittent vancomycin dosing and steady-state concentrations for continuous vancomycin dosing were measured. NONMEM 7.3 was used for population pharmacokinetic analysis. Monte Carlo simulations were performed to compare dosing schemes. RESULTS: Data from 54 infants were used for model development and from 34 infants for the model evaluation {corrected gestational age [median (range)] = 29 (23.7-41.9) weeks and 28 (23.4-41.7) weeks, respectively}. The final model was a one-compartment model. Weight and postmenstrual age were included a priori, and then no additional covariate significantly improved the model fit. Final model parameter estimates [mean (SEM)]: CL = 5.7 (0.3) L/h/70 kg and V = 39.3 (3.7) L/70 kg. Visual predictive check of the evaluation dataset confirmed the model can predict external data. Simulations using MIC of 1 mg/L showed that for neonates with gestational age ≤25 weeks and postnatal age ≤2 weeks AUC24,ss/MIC was lower with the intermittent regimen (median 482 versus 663). CONCLUSIONS: A population pharmacokinetic model for continuous and intermittent vancomycin administration in infants was developed. Continuous administration might be favourable for treating infections caused by resistant microorganisms in very young and immature infants.

Type: Article
Title: Development and external evaluation of a population pharmacokinetic model for continuous and intermittent administration of vancomycin in neonates and infants using prospectively collected data
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jac/dky525
Publisher version: https://doi.org/10.1093/jac/dky525
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Vancomycin, gestational age, infant, newborn
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10072224
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