Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies.
Title | Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Germovsek, E., Lutsar I., Kipper K., Karlsson M. O., Planche T., Chazallon C., Meyer L., Trafojer U. M. T., Metsvaht T., Fournier I., Sharland M., Heath P., & Standing J. F. |
Corporate Authors | NeoMero Consortium |
Journal | J Antimicrob Chemother |
Volume | 73 |
Issue | 7 |
Pagination | 1908-1916 |
Date Published | 2018 07 01 |
ISSN | 1460-2091 |
Keywords | Anti-Bacterial Agents, Europe, Female, Gram-Negative Bacterial Infections, Humans, Infant, Infant, Newborn, Infusions, Intravenous, Male, Meningitis, Bacterial, Meropenem, Monte Carlo Method, Neonatal Sepsis, Sepsis |
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. |
DOI | 10.1093/jac/dky128 |
Alternate Journal | J Antimicrob Chemother |
PubMed ID | 29684147 |
PubMed Central ID | PMC6005047 |
Grant List | G1002305 / MRC_ / Medical Research Council / United Kingdom / DH_ / Department of Health / United Kingdom |