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CSF concentration of cefotaxime in adult patients with pneumococcal meningitis: a multicentre retrospective study
Paul Le Turnier1,2, Najoua El Helali3, Romain Guilhaumou4,5
1Department of Infectious Diseases, Nantes University Hospital, Nantes, France.
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.
Insights
High-dose cefotaxime (200 mg/kg/day) achieved excellent cerebrospinal fluid (CSF) concentrations in adults with pneumococcal meningitis, demonstrating favorable pharmacodynamics and tolerability for treating this serious infection.
Area of Science:
- Infectious Diseases
- Pharmacology
- Clinical Microbiology
Background:
- Pneumococcal meningitis is a severe infection requiring effective antibiotic penetration into the cerebrospinal fluid (CSF).
- Limited data exist on cefotaxime CSF concentrations during adult Streptococcus pneumoniae meningitis.
- Understanding cefotaxime pharmacokinetics in the CSF is crucial for optimizing treatment outcomes.
Purpose of the Study:
- To determine CSF concentrations of cefotaxime in adult patients treated for pneumococcal meningitis.
- To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) parameters of high-dose cefotaxime in this patient population.
- To assess the tolerability and safety profile of high-dose cefotaxime monotherapy.
Main Methods:
- A multicentre, observational, retrospective study of adult patients with S. pneumoniae meningitis.
- Review of 44 CSF samples from 31 patients treated with high-dose cefotaxime (median 15g/day or 200 mg/kg/day).
- Analysis of cefotaxime concentrations, minimum inhibitory concentrations (MICs) of S. pneumoniae, and CSF/MIC ratios.
Main Results:
- Median cefotaxime CSF concentration was 10.3 mg/L, with 81% of samples exceeding 10 times the MIC.
- The median CSF/MIC ratio was 38, indicating robust antimicrobial activity.
- High-dose cefotaxime was generally well-tolerated, with discontinuation due to toxicity in only two patients.
Conclusions:
- High-dose cefotaxime (200 mg/kg/day) yields elevated CSF concentrations in adult pneumococcal meningitis.
- The observed PK/PD parameters and tolerability are reassuring for the use of high-dose cefotaxime monotherapy.
- This study provides valuable pharmacological data supporting cefotaxime efficacy against susceptible S. pneumoniae strains.
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