Comparative activity of fluorinated quinolones in acute and subacute Streptococcus pneumoniae pneumonia models: efficacy of temafloxacin.

We have compared the efficacy of temafloxacin against Streptococcus pneumoniae in experimental murine pneumonia models with that of ofloxacin and ciprofloxacin. Erythromycin and amoxycillin were used as reference agents. Two different strains of mice were used: Swiss mice develop acute pneumonia and die within three to four days, while C57B1/6 mice develop subacute pneumonia and die within eight to ten days. In both cases all animals quickly become bacteraemic. Mice were infected with approximately 10(5) cfu of a virulent S. pneumoniae strain, serotype 3 (P4241), by the intra-tracheal per oral route. In Swiss mice, subcutaneous treatments were initiated early (18 h post-infection) and given every 12 h for 72 h. A 79% cumulative survival rate was obtained in temafloxacin-treated mice (50 mg/kg); a figure not significantly different from those for erythromycin and amoxycillin but far higher than those for ofloxacin and ciprofloxacin (7% survivors). Pulmonary clearance of bacteria was consistent with the survival rates. Complete clearance of bacteria in the lungs and blood was achieved using temafloxacin (50 mg/kg), whereas mice remained bacteraemic even with increased dosages of ofloxacin and ciprofloxacin. In the subacute pneumonia C57B1/6-mice model, the superior efficacy of temafloxacin (compared to ofloxacin and ciprofloxacin) was also seen even when treatment was initiated at late stages of the disease (up to 96 h post-infection). The pharmacokinetics of temafloxacin account for its better efficacy against S. pneumoniae pneumonia relative to the other quinolones.