EFFICACY OF TROVAFLOXACIN AGAINST PENICILLIN-SUSCEPTIBLE AND MULTIRESISTANT STRAINS OF STREPTOCOCCUS-PNEUMONIAE IN A MOUSE PNEUMONIA MODEL

The increasing emergence of penicillin-resistant and multidrug-resista nt strains of Streptococcus pneumoniae will create a serious therapeut ic problem in coming years. Trovafloxacin is a novel naphthyridone qui nolone with promising activity against S. pneumoniae, including penici llin-resistant strains (MIC for 90% of the isolates tested, 0.25 mu g/ ml). We compared its in vivo efficacy with that of other fluoroquinolo nes (ciprofloxacin, temafloxacin, and sparfloxacin) and a reference be ta-lactam (amoxicillin) in a model of acute experimental pneumonia. Im munocompetent Swiss mice were infected by peroral tracheal delivery of a virulent, penicillin-susceptible strain (MIC, 0.03 mu g/ml); leukop enic Swiss mice were infected with three poorly virulent, penicillin-r esistant strains (MICs, 4 to 8 mu g/ml) and a ciprofloxacin-resistant strain (MIC, 32 mu g/ml). Treatments were started 6 h (immunocompetent mice) or 3 h (leukopenic mice) after infection. Doses ranging from 12 .5 to 300 mg/kg were given at 12- or 8-h intervals for 3 days. Trovafl oxacin (25 mg/kg) was the most effective agent in vivo against penicil lin-susceptible and -resistant strains. Corresponding survival rates w ere 2- to 4-fold higher than with 50-mg/kg sparfloxacin or temafloxaci n and 8- to 16-fold higher than with 100-mg/kg ciprofloxacin. The rati os of the area under the concentration-time curve to the MIC in serum and lung tissue were more favorable with trovafloxacin than with the o ther quinolones. Efficacy in vivo correlated with pharmacokinetic para meters. Trovafloxacin shows potential for the treatment of infections due to penicillin-susceptible and -resistant S. pneumoniae but appears to be ineffective against a ciprofloxacin-resistant strain.