Evaluation of cefepime alone and in combination with vancomycin against penicillin-resistant pneumococci in the rabbit meningitis model and in vitro

Cefepime, a broad-spectrum, fourth-generation cephalosporin, showed excelle nt CSF penetration with levels ranging between 10 and 16 mg/L after two int ravenous injections (100 mg/kg). The bactericidal activity of cefepime (-0. 60 +/- 0.28 Delta log(10) cfu/mL/h) was superior to that of ceftriaxone (-0 .34 +/- 0.23 Delta log(10) cfu/mL/h, P < 0.05) and vancomycin (-0.39 +/- 0. 19 Delta log(10) cfu/mL/h, P < 0.05) in the treatment of rabbits with menin gitis caused by an isolate highly resistant to penicillin (MIC of penicilli n G: 4 mg/L). The addition of vancomycin to both cephalosporins did not sig nificantly increase the killing rate compared with monotherapies (P > 0.05) . Similar results were obtained in time-killing experiments in vitro.