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J Antimicrob Chemother. 2018 Jul 1;73(7):1908-1916. doi: 10.1093/jac/dky128.

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

Author information

1
Department of Infection, Inflammation and Rheumatology, Great Ormond Street Institute of Child Health, University College London, London, UK.
2
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
3
Department of Microbiology, University of Tartu, Tartu, Estonia.
4
Institute for Infection and Immunity, St George's, University of London, Cranmer Terrace, London, UK.
5
INSERM SC10-US019, Villejuif, France.
6
Neonatal Intensive Care Unit, Department for Women and Child Health, University of Padua, Padua, Italy.
7
Tartu University Hospital, Tartu, Estonia.

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.

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