Grepafloxacin against penicillin-resistant pneumococci in the rabbit meningitis model

Grepafloxacin, a new fluoroquinolone, produced bactericidal activity compar able to that of vancomycin and ceftriaxone in the treatment in rabbits of m eningitis caused by a pneumococcal strain highly resistant to penicillin (M IC 4 mg/L) (Delta log(10) cfu/mL.h for grepafloxacin, -0.32 +/- 0.15; dose, 15 mg/kg iv; Delta log(10) cfu/mL.h for vancomycin, -0.39 +/- 0.18; dose, 2 x 20 mg/kg iv; Delta log(10) cfu/mL.h for ceftriaxone, -0.32 +/- 0.12; do se, 125 mg/kg iv). Higher doses of grepafloxacin (30 mg/kg and 2 x 50 mg/kg ) did not improve the killing rates. The combination of grepafloxacin with vancomycin was not significantly superior to monotherapies (P > 0.05). In v itro, grepafloxacin was bactericidal at concentrations above the MIC. Using concentrations around the MIC, addition of vancomycin to grepafloxacin sho wed synergic activity.