EFFICACY OF CS-834 AGAINST EXPERIMENTAL PNEUMONIA CAUSED BY PENICILLIN-SUSCEPTIBLE AND PENICILLIN-RESISTANT STREPTOCOCCUS-PNEUMONIAE IN MICE

The efficacy of CS-834, a novel oral carbapenem, was assessed by using a murine model of pneumonia caused by penicillin-susceptible and peni cillin-resistant Streptococcus pneumoniae and was compared with those of oral cephems, i.e., cefteram pivoxil, cefpodoxime proxetil, cefdini r, and cefditoren pivoxil, Intranasal inoculation of 10(6) CFU of peni cillin-susceptible or penicillin-resistant S. pneumoniae in the expone ntial growth phase induced pneumonia and bacteremia in ddY mice within 48 h, For the treatment of infections caused by the penicillin-suscep tible strain the antibiotics were administered orally at 0.4, 2, and 1 0 mg/kg of body weight twice daily for 2 days beginning at 24 h after bacterial inoculation, and for the treatment of infections caused by a penicillin-resistant strain the antibiotics were administered at 2, 1 0, and 50 mg/kg twice daily for 2 days beginning at 24 h after bacteri al inoculation, Among the antibiotics tested, CS-834 exhibited the mos t potent efficacy against both types of strains, Against infections ca used by penicillin susceptible S. pneumoniae, CS-834 at all doses sign ificantly reduced the numbers of viable cells in both the lungs and bl ood, Cefpodoxime proxetil at all doses and cefteram pivoxil and cefdit oren pivoxil at doses of 2 and 10 mg/kg showed comparable efficacies. Against infections caused by penicillin-resistant S. pneumoniae, CS-83 4 at doses of 10 and 50 mg/kg showed the most potent efficacy among th e antibiotics tested, resulting in the maximum decrease in the numbers of viable cells in the lungs. Comparable efficacies were observed wit h cefteram pivoxil and cefpodoxime proxetil at doses of 50 mg/kg each, The concentration of CS-834 in the lungs and blood was higher than th at of cefdinir and was lower than those of the other antibiotics teste d, suggesting that the potent therapeutic efficacy of CS-834 reflects its strong activity against S. pneumoniae.