EVALUATION OF ANTIMICROBIAL REGIMENS FOR TREATMENT OF EXPERIMENTAL PENICILLIN-RESISTANT AND CEPHALOSPORIN-RESISTANT PNEUMOCOCCAL MENINGITIS

The most appropriate therapy for meningitis caused by Streptococcus pn eumoniae strains resistant to the extended-spectrum cephalosporins is unknown. We evaluated ceftriaxone, vancomycin, and rifampin alone and in different combinations and meropenem, cefpirome, and clinafloxacin alone in the rabbit meningitis model. Meningitis was induced in rabbit s by intracisternal inoculation of one of two pneumococcal strains iso lated from infants with meningitis (ceftriaxone MICs, 4 and 1 mug/ml, respectively). Two doses, 5 h apart, of each antibiotic were given int ravenously (except that ceftriaxone was given as one dose). Cerebrospi nal fluid bacterial concentrations were measured at 0, 5, 10, and 24 h after therapy was started. Clinafloxacin was the most active single a gent against both strains. Against the more resistant strain, ceftriax one or meropenem alone was ineffective. The combination of vancomycin and ceftriaxone was synergistic, suggesting that this combination migh t be effective for initial empiric therapy of pneumococcal meningitis until results of susceptibility studies are available.