TROVAFLOXACIN (CP-99,219), A NEW AZABICYCLO-NAPHTHYRIDONE ANTIMICROBIAL - INHIBITORY AND BACTERICIDAL ACTIVITY AGAINST CLINICAL ISOLATES OFPENICILLIN-SUSCEPTIBLE AND PENICILLIN-RESISTANT STREPTOCOCCUS-PNEUMONIAE

With the continued increase in numbers of Streptococcus pneumoniae str ains resistant to multiple antimicrobials, new agents are needed for t herapy. This study was performed to assess the in vitro activity of tr ovafloxacin, a new fluorinated quinolone, against penicillin-susceptib le and -resistant Streptococcus pneumoniae. By means of a broth microd ilution method, the inhibitory activity was determined for several ant imicrobials against 481 strains of S. pneumoniae: 336 penicillin susce ptible, 109 intermediately resistant to penicillin, and 36 fully penic illin resistant. Bactericidal activity was determined through time-kil l kinetic studies. Trovafloxacin was highly active against all test st rains, regardless of increased resistance to penicillin, and exhibited minimum inhibitory concentrations (MIC(90)s) of 0.06 to 0.12 mu g/mL. Trovafloxacin was 8- to 32-fold more active than ciprofloxacin and of loxacin and had 16-fold or higher activity than cefotaxime, ceftriaxon e, cefaclor, amoxicillin/clavulanate, erythromycin, and clarithromycin . Trovafloxacin was also equally active against isolates exhibiting re sistance to multiple antimicrobials. Time-kill kinetic studies showed that both trovafloxacin and ciprofloxacin were bactericidal at four an d eight times MIC values against all S. pneumoniae strains, although t rovafloxacin was appreciably more active in an activity-per-weight com parison. These studies indicate that trovafloxacin may potentially be useful in the treatment of infections, such as sepsis and pneumonia, c aused by multiresistant strains of S. pneumoniae.