Should we reconsider cefazolin for treating staphylococcal meningitis? A retrospective analysis of cefazolin and cloxacillin CSF levels in patients treated for staphylococcal meningitis.

Abstract Objectives The main objective of the study was to assess the meningeal penetration of cefazolin and cloxacillin in patients treated for methicillin-susceptible staphylococcal meningitis. Methods We retrospectively identified patients treated for Staphylococcus meningitis with measurements of cefazolin or cloxacillin concentrations in cerebrospinal fluid (CSF) using a liquid-chromatography coupled with mass-spectrometry validated assay at the Nantes University Hospital between January 2009 and October 2019. Staphylococcus meningitis was defined by a compatible clinical presentation and a microbiological confirmation (positive CSF culture or positive specific polymerase chain reaction). Medical charts were retrospectively reviewed to collect microbiological, clinical data and to assess therapeutic success. Results Among the 17 included patients, 8 (47%) were treated with cefazolin and 9 (53%) with cloxacillin. Median daily dosages of cefazolin and cloxacillin were 8 (range 6-12) and 12 (range 10-13) grams respectively. Cefazolin and cloxacillin were mainly administered via continuous infusion. Eleven patients (65%) were males, median (IQR) age was 54 years (50;70), 14 (82%) had post-operative meningitis and 3 (18%) hematogenous meningitis. Median (IQR) antibiotic CSF concentrations were 2.8 (2.1;5.2) and 0.66 (0.5;0.9) mg/L for cefazolin and cloxacillin groups respectively. Cloxacillin was discontinued in 2 patients for therapeutic failure. Conclusions Patients with staphylococcal meningitis treated with high-dose continuous intravenous infusion of cefazolin achieved therapeutic concentrations in CSF. Cefazolin appears to be a therapeutic candidate which should be properly evaluated in this indication.