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Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies.

Germovsek, E; Lutsar, I; Kipper, K; Karlsson, MO; Planche, T; Chazallon, C; Meyer, L; Trafojer, UMT; Metsvaht, T; Fournier, I; et al. Germovsek, E; Lutsar, I; Kipper, K; Karlsson, MO; Planche, T; Chazallon, C; Meyer, L; Trafojer, UMT; Metsvaht, T; Fournier, I; Sharland, M; Heath, P; Standing, JF; NeoMero Consortium (2018) Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies. J Antimicrob Chemother, 73 (7). pp. 1908-1916. ISSN 1460-2091 https://doi.org/10.1093/jac/dky128
SGUL Authors: Heath, Paul Trafford Sharland, Michael Roy

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Abstract

Background: Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking. Objectives: To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS). Methods: Data were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed. Results: A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome. Conclusions: Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered.

Item Type: Article
Additional Information: © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Microbiology, 1115 Pharmacology And Pharmaceutical Sciences, 0605 Microbiology, 1108 Medical 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
July 2018Published
19 April 2018Published Online
12 March 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
242146Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
G1002305Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 29684147
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109753
Publisher's version: https://doi.org/10.1093/jac/dky128

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