Efficacy of gatifloxacin alone and in combination with cefepime against penicillin-resistant Streptococcus pneumoniae in a rabbit meningitis model and in vitro

Gatifloxacin penetrated well into cerebrospinal fluid (CSF) (49 +/- 11%), m easured by comparison of AUC(CSF)/AUC(serum), and showed good bactericidal activity (leading to a decrease of 0.75 +/- 0.17 log(10) cfu/mL/h) in the t reatment of experimental meningitis in rabbits caused by a penicillin-resis tant pneumococcal strain (MIC 4 mg/L), It was significantly more effective than the standard regimen, ceftriaxone with vancomycin, which led to a decr ease of 0.53 +/- 0.17 log(10) cfu/mL/h, The addition of cefepime to gatiflo xacin slightly improved the killing rates (giving a decrease of 0.84 +/- 0. 14 log(10) cfu/mL/h), In vitro, synergy was demonstrated between cefepime a nd gatifloxacin by the chequerboard method (fractional inhibitory concentra tion index = 0.5) and by viable counts over 8 h.