This study was planned to compare the efficacy of ceftriaxone + vancomycin with ceftriaxone + rifampicin in a rabbit model of penicillin and cephalosporin-resistant Streptococcus pneumoniae meningitis. Meningitis was induced by intracisternal inoculation of S. pneumoniae. After 18 h of incubation, Group I was given saline solution (control group), whilst Groups 2 and 3 were given ceftriaxone + vancomycin and ceftriaxone + rifampicin, respectively. Cerebrospinal fluid bacterial concentrations were, measured at 0, 2, 12, 14 and 24 h after therapy was initiated.. In the control group, bacterial growth was present at all time points, whereas no growth was observed in either the ceftriaxone + vancomycin group or the ceftriaxone + rifampicin group after 2 h of therapy. Ceftriaxone + rifampicin was found to be as effective as ceftriaxone + vancomycin in the treatment of penicillin-resistant S. pneumoniae meningitis in experimental rabbit model. (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.