Evaluation of a triple-drug combination for treatment of experimental multidrug-resistant pneumococcal meningitis

To evaluate the therapeutic efficacy of ceftriaxone+vancomycin+rifampicin (CVR) in the treatment of pneumococcal meningitis caused by a multidrug-resistant strain, single-drug regimens (ceftriaxone 100 mg/kg, rifampicin 15 mg/kg, or vancomycin 20 mg/kg), double-drug regimens (ceftriaxone+vancomycin [CV] and ceftriaxone+rifampicin [CR]) and a triple-drug combination (CVR) with or without dexamethasone were compared in a rabbit meningitis model. Meningitis was induced by a highly penicillin-resistant (MIC 2 mg/l) and ceftriaxone-resistant (MIC 4 mg/l) pneumococcal strain. Final therapeutic efficacy was evaluated by the bacterial concentration at 24 h, and the bacterial killing rate was also evaluated. All combination regimens were superior to ceftriaxone or vancomycin single-drug regimens with regard to sterilisation of CSF and bacterial killing rate. Rifampicin was as effective as combination regimens. Regardless of dexamethasone, therapeutic efficacy of CVR and CR were superior to that of CV. CVR showed comparable therapeutic efficacy to CR. Data suggested that CVR would not have additional therapeutic benefit over CR during the initial 24 h of treatment.