Synergy between trovafloxacin and ceftriaxone against penicillin-resistantpneumococci in the rabbit meningitis model and in vitro

The bactericidal activities of monotherapy with trovafloxacin (-0.37 +/- 1. 15 Delta log(10) CFU/ml.h), vancomycin (-0.32 +/- 0.12 Delta log(10) CFU/ml .h), and ceftriaxone (-0.36 +/- 0.19 Delta log(10) CFU/ml.h) for the treatm ent of experimental meningitis in rabbits due to a clinical penicillin-resi stant pneumococcal strain (MIC, 4 mg/liter) were similar. The combination o f ceftriaxone with trovafloxacin considerably improved the killing rates (- 0.67 +/- 0.16 Delta log(10) CFU/ml.h) and was slightly superior to ceftriax one with vancomycin (killing rate, -0.53 +/- 0.22 Delta log(10) CFU/ml.h), the regimen most commonly used in clinical practice. In vitro, synergy was demonstrated between ceftriaxone and trovafloxacin by the checkerboard meth od (fractional inhibitory concentration index, 0.5) and by time-killing ass ays over 8 h.