Protective effect of trovafloxacin, ciprofloxacin and ampicillin against Streptococcus pneumoniae in a murine sepsis model

Abstract

Trovafloxacin is a new fluoroquinolone that has potent microbiological activity against the pneumococcus, including penicillin-resistant strains. To evaluate the protective effect of trovafloxacin, ciprofloxacin and ampicillin against penicillin-susceptible, -intermediate and -resistant strains of Streptococcus pneumoniae, an intraperitoneal, immunocompetent mouse model of sepsis was used. The minimum lethal dose (MLD) for each isolate was determined in duplicate. A single sc dose of each antibiotic was administered over a wide range of doses 1 h after the ip inoculation of the test isolate at the MLD. The assessment of the protective dose for 50% of the population (PD50) for each antimicrobial/bacteria combination was performed in triplicate and the PD50 value was calculated at the end of 5 days. Results showed that trovafloxacin provided PD50 values that were significantly lower than those of ciprofloxacin for all isolates. For the penicillin-susceptible and -intermediate isolates, the PD50 values of ampicillin were significantly lower than those for either of the fluoroquinolones studied; however, trovafloxacin was statistically superior to both ciprofloxacin and ampicillin against the penicillin-resistant strain. Therefore, regardless of penicillin susceptibility, trovafloxacin has potent activity against Streptococcus pneumoniae and may be a viable alternative for the treatment of penicillin-resistant isolates.