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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; ... NeoMero Consortium; + view all (2018) Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies. Journal of Antimicrobial Chemotherapy , Article dky128. 10.1093/jac/dky128. Green open access

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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.

Type: Article
Title: Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jac/dky128
Publisher version: https://doi.org/10.1093/jac/dky128
Language: English
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: Cerebrospinal fluid proteins infant newborn plasma pharmacokinetics meropenem
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/10048314
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