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

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Germovsek, EvaUppsala universitet,Institutionen för farmaceutisk biovetenskap,UCL, Great Ormond St Inst Child Hlth, Dept Infect Inflammat & Rheumatol, London, England (author)

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

Article/chapterEnglish2018

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2018-04-19
Oxford University Press (OUP),2018
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LIBRIS-ID:oai:DiVA.org:uu-361548
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-361548URI
https://doi.org/10.1093/jac/dky128DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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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.

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MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Pediatrik hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Pediatrics hsv//eng

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Lutsar, IrjaUniv Tartu, Dept Microbiol, Tartu, Estonia (author)
Kipper, KarinUniv Tartu, Dept Microbiol, Tartu, Estonia; St Georges Univ London, Inst Infect & Immun, Cranmer Terrace, London, England (author)
Karlsson, Mats OUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)matskarl (author)
Planche, TimSt Georges Univ London, Inst Infect & Immun, Cranmer Terrace, London, England (author)
Chazallon, CorineINSERM SC10 US019, Villejuif, France (author)
Meyer, LaurenceINSERM SC10 US019, Villejuif, France (author)
Trafojer, Ursula M. T.Univ Padua, Dept Women & Child Hlth, Neonatal Intens Care Unit, Padua, Italy (author)
Metsvaht, TuuliTartu Univ Hosp, Tartu, Estonia (author)
Fournier, IsabelleINSERM SC10 US019, Villejuif, France (author)
Sharland, MikeSt Georges Univ London, Inst Infect & Immun, Cranmer Terrace, London, England (author)
Heath, PaulSt Georges Univ London, Inst Infect & Immun, Cranmer Terrace, London, England (author)
Standing, Joseph F.St Georges Univ London, Inst Infect & Immun, Cranmer Terrace, London, England; UCL, Great Ormond St Inst Child Hlth, Dept Infect Inflammat & Rheumatol, London, England (author)
Uppsala universitetInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

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In:Journal of Antimicrobial Chemotherapy: Oxford University Press (OUP)73:7, s. 1908-19160305-74531460-2091

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