CSF concentration of cefotaxime in adult patients with pneumococcal meningitis: a multicentre retrospective study
2021
Le Turnier, Paul | El Helali, Najoua | Guilhaumou, Romain | Pilmis, Benoit | Revest, Matthieu | Velly, Lionel | Leroy, Anne-Gaëlle | Duval, Xavier | Lemaitre, Florian | Grégoire, Matthieu | Bennis, Youssef | Centre d’Investigation Clinique de Nantes (CIC Nantes) ; Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes) | Centre hospitalier Saint-Joseph [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Institut de Neurosciences des Systèmes (INS) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM) | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Centre Hospitalier Universitaire [Rennes] | Centre d'Investigation Clinique [Rennes] (CIC) ; Université de Rennes (UR)-Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]-Institut National de la Santé et de la Recherche Médicale (INSERM) | ARN régulateurs bactériens et médecine (BRM) ; Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique) | Institut de Neurosciences de la Timone (INT) ; Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS) | Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes) | Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425) ; AP-HP - Hôpital Bichat - Claude Bernard [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM) | F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC) | Institut de recherche en santé, environnement et travail (Irset) ; Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique) | École des Hautes Études en Santé Publique [EHESP] (EHESP) | The Enteric Nervous System in gut and brain disorders [U1235] (TENS) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN)-Université de Nantes (UN) | DIFCEFO study group | Mécanismes physiopathologiques et conséquences des calcifications cardiovasculaires - UR UPJV 7517 (MP3CV) ; Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie | Assistance Publique Hopitaux de Paris, French Ministry of Health, Institut national de la santé et de la recherche médicale (Inserm), Société de Pathologie Infectieuse de Langue Française (SPILF) and the Pfizer Pharmaceutical company
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Show more [+] Less [-]English. 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.
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