In vivo efficacy of a new fluoroquinolone, sparfloxacin, against penicillin-susceptible and -resistant and multiresistant strains of Streptococcus pneumoniae in a mouse model of pneumonia

Abstract

The increasing emergence of penicillin-resistant and multiresistant strains of Streptococcus pneumoniae may pose a problem in coming years. We therefore compared sparfloxacin, a new fluoroquinolone with improved potency against streptococci, with amoxicillin, the "gold standard" in this setting, and another fluoroquinolone, ciprofloxacin, in a mouse pneumonia model. Their efficacies against penicillin-susceptible (serotype 3), macrolide-resistant (serotype 1), penicillin-resistant (serotype 23), and multiresistant (serotype 6) S. pneumoniae strains were evaluated. Immunocompetent Swiss mice (serotypes 1 and 3) and leukopenic mice (serotypes 6 and 23) were infected by peroral tracheal delivery of 10(4) to 10(6) CFU. Subcutaneous injections of antibiotics were initiated at 6, 18, 48, or 72 h after infection (six injections at 12-h intervals). In the immunocompetent mice, 100% survival was obtained with sparfloxacin (50 mg/kg) and amoxicillin (5 mg/kg) against both penicillin-susceptible and macrolide-resistant strains; ciprofloxacin gave significantly lower survival rates. Two to four injections of sparfloxacin completely cleared bacteria from lungs and blood; the most rapid eradication was achieved with amoxicillin. Sparfloxacin also fully protected leukopenic mice against penicillin-resistant strains. The dose of amoxicillin (50 mg/kg) required to protect mice and eradicate penicillin-resistant and multiresistant strains was 10 times higher than that effective against penicillin-susceptible strains. The microbiological and pharmacokinetic properties of sparfloxacin (e.g., the time during which concentrations exceed the MIC of the test pathogen) accounted for its efficacy against susceptible and resistant strains of S. pneumoniae in this model.