In vitro susceptibilities to and bactericidal activities of garenoxacin (BMS-284756) and other antimicrobial agents against human mycoplasmas and ureaplasmas

Abstract

The in vitro susceptibilities to garenoxacin (BMS-284756), an investigational des-fluoroquinolone, and eight other agents were determined for 63 Mycoplasma pneumoniae, 45 Mycoplasma hominis, 15 Mycoplasma fermentans, and 68 Ureaplasma sp. isolates. Garenoxacin was the most active quinolone, inhibiting all isolates at <or=1 microg/ml. The garenoxacin MIC at which 90% of isolates are inhibited (MIC(90)s; <or=0.008 microg/ml) was at least 4-fold less than those of moxifloxacin and clindamycin, 8-fold less than that of sparfloxacin, and 64-fold less than those of levofloxacin and ciprofloxacin for M. pneumoniae. For M. hominis, the garenoxacin MIC(90) (<or=0.008 microg/ml) was 4-fold less than those of clindamycin and moxifloxacin, 8-fold less than that of sparfloxacin, and 64-fold less than those of levofloxacin and ciprofloxacin. All 15 M. fermentans isolates were inhibited by garenoxacin at concentrations <or=0.008 microg/ml, making it the most active drug tested against this organism. For Ureaplasma spp., the garenoxacin MIC(90) (0.25 microg/ml) was equivalent to those of moxifloxacin and doxycycline, 4-fold less than those of levofloxacin and sparfloxacin, 8-fold less than that of azithromycin, and 32-fold less than that of ciprofloxacin. Garenoxacin and the other fluoroquinolones tested were demonstrated to have bactericidal activities against M. pneumoniae and M. hominis by measurement of minimal bactericidal activities and by time-kill studies. Further study of garenoxacin is required, as it has great potential for use in the treatment of infections due to mycoplasmas and ureaplasmas.

FIG. 1.

(a) Time-kill graph for an isolate of M. pneumoniae (MIC, 0.032 μg/ml) against which the activities of garenoxacin at concentrations one to eight times the MIC were tested. Bactericidal effects were demonstrated at eight times the MIC after 24 h of incubation; at two, four, and eight times the MIC after 48 h of incubation; and at all concentrations after 96 h of incubation. Regrowth of ≤2 log₁₀ CFU was observed in the presence of some of the lower concentrations of antimicrobials after 120 and 144 h of incubation. (b) Time-kill graph for an isolate of M. hominis (MIC, 0.008 μg/ml) against which the activities of garenoxacin at concentrations one to eight times the MIC were tested. Bactericidal effects were demonstrated at four and eight times the MIC after 24 h of incubation; and bactericidal effects were demonstrated at two, four, and eight times the MIC after 48 h of incubation. Regrowth of 1 log₁₀ CFU was observed after 48 h of incubation at the concentration equal to the MIC.