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

OBJECTIVES: To assess the meningeal penetration of cefazolin and cloxacillin in individuals treated for methicillin-susceptible staphylococcal meningitis. METHODS: We retrospectively identified individuals treated for Staphylococcus meningitis with measurements of cefazolin or cloxacillin concentrations in cerebrospinal fluid (CSF) using a validated assay of liquid chromatography coupled with mass spectrometry 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 PCR). Medical charts were retrospectively reviewed to collect microbiological and clinical data, and to assess therapeutic success. RESULTS: Among the 17 included individuals, eight (47%) were treated with cefazolin and nine (53%) with cloxacillin. Median daily dosages of cefazolin and cloxacillin were 8 g (range 6-12 g) and 12 g (range 10-13 g), respectively. Cefazolin and cloxacillin were mainly administered by continuous infusion. Eleven individuals (65%) were men, median (interquartile range (IQR)) age was 54 years (50; 70), 14 (82%) had postoperative meningitis and 3 (18%) had haematogenous meningitis. Median (IQR) antibiotic CSF concentrations were 2.8 mg/L (2.1; 5.2) and 0.66 mg/L (0.5; 0.9) for cefazolin and cloxacillin groups, respectively. Cloxacillin was discontinued in two individuals 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 that should be properly evaluated in this indication.

Characteristics and outcome of multidrug-resistant tuberculosis in a low-incidence area.

OBJECTIVES: To characterize multidrug-resistant tuberculosis (MDR-TB) patients treated in a low endemic area in France and to determine risk factors for resistance. We also analyzed the efficacy and tolerability of tuberculosis (TB) treatment. METHODS: Between 2002-2013, all MDR-TB patients diagnosed in western France (hospitals belonging to the GERICCO group) were retrospectively included, with a follow-up period running until 2016. A case-control study (1:2), matched according to age, sex, and year of diagnosis, was performed to assess socio-demographic and clinical data, treatment strategies, and outcomes for the MDR-TB patients and controls treated for drug-susceptible tuberculosis during the same period. RESULTS: Of 134 TB patients, 44 were MDR-TB and 90 were drug-susceptible TB. Of the 44 MDR-TB patients (35 MDR and nine extensively drug-resistant [XDR]), 33 (75%) were males; the median age was 33 years; and 27 (61%) were born in Eastern Europe. Prior treatment failure was more frequently reported for XDR-TB (8/9) in Georgian patients. In multivariate analysis, risk contacts and prior TB history were associated with MDR-TB. Treatment failure was associated with MDR/XDR-TB and miliary TB. CONCLUSION: In western France, MDR-TB more frequently occurred in recent migrants from high-risk countries with a previous history of at-risk contact with other MDR-TB patients or previous TB treatment failure.