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

Abstract
Cefepime, a broad-spectrum, fourth-generation cephalosporin, showed excellent CSF penetration with levels ranging between 10 and 16 mg/L after two intravenous injections (100 mg/kg). The bactericidal activity of cefepime (–0.60 ± 0.28 Δlog10 cfu/mL/h) was superior to that of ceftriaxone (–0.34 ± 0.23 Δlog10 cfu/mL/h, P < 0.05) and vancomycin (–0.39 ± 0.19 Δlog10 cfu/mL/h, P < 0.05) in the treatment of rabbits with meningitis caused by an isolate highly resistant to penicillin (MIC of penicillin G: 4 mg/L). The addition of vancomycin to both cephalosporins did not significantly increase the killing rate compared with monotherapies (P > 0.05). Similar results were obtained in time–killing experiments in vitro.

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