CSF concentration of cefotaxime in adult patients with pneumococcal meningitis: a multicentre retrospective study.


Journal

The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617

Informations de publication

Date de publication:
12 08 2021
Historique:
received: 17 04 2021
accepted: 10 05 2021
pubmed: 14 6 2021
medline: 29 10 2021
entrez: 13 6 2021
Statut: ppublish

Résumé

Pneumococcal meningitis is a devastating disease that requires adequate meningeal antibiotic penetration to limit the mortality. Despite a large usage in this indication, data about CSF concentration of cefotaxime during pneumococcal meningitis in adults are scarce. Therefore, we aimed to describe the CSF concentration obtained after high-dose cefotaxime administration in adult patients treated for Streptococcus pneumoniae meningitis. In this multicentre, observational, retrospective study, cases of adult patients with S. pneumoniae meningitis hospitalized between January 2013 and October 2019 for whom cefotaxime concentration was measured in CSF were reviewed. Cefotaxime concentration was analysed in 44 CSF samples collected among 31 patients. Median (IQR) age was 61 years (52-69). Dexamethasone was administered in 27 subjects. Median (IQR) cefotaxime daily dosage was 15 g (12-19), corresponding to 200 mg/kg (150-280). CSF samples were collected approximately 5 days after cefotaxime initiation. Median (IQR, range) cefotaxime CSF concentration was 10.3 mg/L (4.8-19.3, 1.2-43.4). Median (range) MIC for Streptococcus pneumoniae was 0.25 mg/L (0.008-1) (n = 22). The median (IQR, range) CSF/MIC ratio was 38 (12-146, 4-1844). Twenty-five CSF concentrations (81%) were above 10 times the MIC. Cefotaxime was discontinued in two patients for toxicity. In-hospital mortality rate was 29%. Adult patients with pneumococcal meningitis treated with a high dose of cefotaxime (200 mg/kg/day) had elevated CSF concentrations with satisfying pharmacokinetics/pharmacodynamics parameters and tolerability profile. This study brings reassuring pharmacological data regarding the use of high-dose cefotaxime monotherapy for treating pneumococcal meningitis with susceptible strains to cefotaxime.

Sections du résumé

BACKGROUND AND OBJECTIVES
Pneumococcal meningitis is a devastating disease that requires adequate meningeal antibiotic penetration to limit the mortality. Despite a large usage in this indication, data about CSF concentration of cefotaxime during pneumococcal meningitis in adults are scarce. Therefore, we aimed to describe the CSF concentration obtained after high-dose cefotaxime administration in adult patients treated for Streptococcus pneumoniae meningitis.
PATIENTS AND METHODS
In this multicentre, observational, retrospective study, cases of adult patients with S. pneumoniae meningitis hospitalized between January 2013 and October 2019 for whom cefotaxime concentration was measured in CSF were reviewed.
RESULTS
Cefotaxime concentration was analysed in 44 CSF samples collected among 31 patients. Median (IQR) age was 61 years (52-69). Dexamethasone was administered in 27 subjects. Median (IQR) cefotaxime daily dosage was 15 g (12-19), corresponding to 200 mg/kg (150-280). CSF samples were collected approximately 5 days after cefotaxime initiation. Median (IQR, range) cefotaxime CSF concentration was 10.3 mg/L (4.8-19.3, 1.2-43.4). Median (range) MIC for Streptococcus pneumoniae was 0.25 mg/L (0.008-1) (n = 22). The median (IQR, range) CSF/MIC ratio was 38 (12-146, 4-1844). Twenty-five CSF concentrations (81%) were above 10 times the MIC. Cefotaxime was discontinued in two patients for toxicity. In-hospital mortality rate was 29%.
CONCLUSIONS
Adult patients with pneumococcal meningitis treated with a high dose of cefotaxime (200 mg/kg/day) had elevated CSF concentrations with satisfying pharmacokinetics/pharmacodynamics parameters and tolerability profile. This study brings reassuring pharmacological data regarding the use of high-dose cefotaxime monotherapy for treating pneumococcal meningitis with susceptible strains to cefotaxime.

Identifiants

pubmed: 34120184
pii: 6297842
doi: 10.1093/jac/dkab191
doi:

Substances chimiques

Anti-Bacterial Agents 0
Cefotaxime N2GI8B1GK7

Types de publication

Journal Article Multicenter Study Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2352-2355

Investigateurs

Paul Le Turnier (P)
Matthieu Gregoire (M)
Anne-Gaëlle Leroy (AG)
Najoua El-Helali (N)
Benoît Pilmis (B)
Matthieu Revest (M)
Florian Lemaitre (F)
Romain Guilhaumou (R)
Lionel Velly (L)
Jean-Philippe Talarmin (JP)
Jean-Luc Schmit (JL)
Youssef Bennis (Y)
Alexandre Charmillon (A)
Julien Scala-Bertola (J)
Joy Mootien (J)
Solen Kernéis (S)
Firouze Bani-Sadr (F)
Yohan Nguyen (Y)
Zoubir Djerada (Z)
Xavier Duval (X)

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Paul Le Turnier (P)

Department of Infectious Diseases, Nantes University Hospital, Nantes, France.
INSERM CIC 1413, Nantes University Hospital, Nantes, France.

Najoua El Helali (N)

Plateforme de Dosages des Anti-infectieux, Groupe Hospitalier Paris Saint-Joseph, Paris, France.

Romain Guilhaumou (R)

Aix Marseille Univ, Department of Clinical Pharmacology and Pharmacovigilance CIC-CPCET, University Hospital Timone, Marseille, France.
Institut de neurosciences des systèmes, Inserm UMR 1106, Marseille, France.

Benoit Pilmis (B)

Equipe Mobile de Microbiologie Clinique, Groupe Hospitalier Paris Saint-Joseph, Paris, France.
Institut Micalis UMR 1319, Université Paris-Saclay, INRAe, AgroParisTech, Châtenay Malabry, France.

Matthieu Revest (M)

Infectious Diseases and Intensive Care Unit, Rennes University Hospital, Rennes, France.
University of Rennes, Centre d'Investigation Clinique 1414, INSERM, Bacterial Regulatory RNAS and Medicine, Unité Mixte de Recherche 1230, Rennes, France.

Lionel J Velly (LJ)

Aix Marseille Univ, Department of Anaesthesiology and Critical Care Medicine, University Hospital Timone, Marseille, France.
CNRS, INT, Inst Neurosci Timone, UMR7289, Marseille, France.

Anne-Gaëlle Leroy (AG)

Department of Microbiology, Nantes University Hospital, Nantes, France.

Xavier Duval (X)

Paris University, IAME, INSERM, Paris, France.
Inserm Clinical Investigation Centre 1425, Paris, France.
Inserm, F-CRIN, Innovative Clinical Research Network in Vaccinology (I-REIVAC), Paris, France.

Florian Lemaitre (F)

Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), Rennes, France.
UMR_S 1085, F- INSERM, Centre d'Investigation Clinique, CIC 1414, Rennes, France.

Matthieu Gregoire (M)

Clinical Pharmacology Laboratory Department Nantes University Hospital, Nantes, France.
UMR INSERM 1235, The enteric nervous system in gut and brain disorders, University of Nantes, Nantes, France.

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