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

The bactericidal activities of monotherapy with trovafloxacin (-0.37 +/- 0.15 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 treatment of experimental meningitis in rabbits due to a clinical penicillin-resistant pneumococcal strain (MIC, 4 mg/liter) were similar. The combination of ceftriaxone with trovafloxacin considerably improved the killing rates (-0.67 +/- 0.16 Delta log(10) CFU/ml. h) and was slightly superior to ceftriaxone 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 method (fractional inhibitory concentration index, 0.5) and by time-killing assays over 8 h.

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 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 Deltalog(10) cfu/mL/h) was superior to that of ceftriaxone (-0.34 +/- 0.23 Deltalog(10) cfu/mL/h, P < 0.05) and vancomycin (-0.39 +/- 0.19 Deltalog(10) 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.

Trovafloxacin in combination with vancomycin against penicillin-resistant pneumococci in the rabbit meningitis model

Trovafloxacin, a new fluoroquinolone, produced bactericidal activity (-0.33 +/- 0.13 delta log10 CFU/ml.h; intravenously [i.v.] administered dose, 15 mg/kg) comparable to that of vancomycin (-0.39 +/- 0.18 delta log10 CFU/ml.h; i.v. admininistered dose, 20 mg/kg) in the treatment of experimental meningitis in rabbits due to a pneumococcal strain highly resistant to penicillin (MIC of penicillin G, 4 micrograms/ml). The combination of both drugs significantly increased (P < 0.05) the killing rate (-0.60 +/- 0.23 delta log10 CFU/ml.h) compared to that produced by either monotherapy. These results were also confirmed in vitro.