Activity of garenoxacin, an investigational des-F(6)-quinolone, tested against pathogens from community-acquired respiratory tract infections, including those with elevated or resistant-level fluoroquinolone MIC values

Garenoxacin, a novel des-F(6)-quinolone, was tested against 40 423 pathogenic isolates associated with community-acquired respiratory tract infections (CA-RTIs). The strains included Streptococcus pneumoniae (18 887), Haemophilus influenzae (15 555), and Moraxella catarrhalis (5981), each isolated from a significant infection monitored by the SENTRY Antimicrobial Surveillance Program (1999–2005; North America, Latin America, and Europe). All tests were performed by reference broth microdilution methods for garenoxacin and 19 comparison agents. The garenoxacin MIC90 and percentage (%) of strains inhibited at ≤1 μg/mL (proposed susceptible breakpoint) were S. pneumoniae (0.06 μg/mL, >99.9% susceptible), H. influenzae (≤0.03 μg/mL, >99.9%), and M. catarrhalis (≤0.03 μg/mL, 100.0%). The garenoxacin potency versus the pneumococci was 16- to 32-fold greater than levofloxacin or ciprofloxacin and 2-fold superior to moxifloxacin (MIC90, 0.12 μg/mL). Resistances to other classes of antimicrobials did not adversely influence garenoxacin MIC results. Ciprofloxacin- or levofloxacin-resistant (MIC, ≥4 μg/mL) S. pneumoniae had higher garenoxacin MIC90 values (1 μg/mL), but 90.6% to 97.5% of strains remained susceptible. Strains of all 3 monitored pathogens with mutations in the quinolone resistance determining region (QRDR) had higher garenoxacin MIC results, with ≥3 to 4 QRDR mutations required to elevate garenoxacin MIC values to ≥2 μg/mL. In conclusion, garenoxacin possesses a potent activity against pneumococci, H. influenzae, and M. catarrhalis strains worldwide, at a level significantly greater than the available tested agents in the fluoroquinolone class (ciprofloxacin, levofloxacin, and moxifloxacin). Only 13 and 4 isolates (0.07% and 0.03%) of S. pneumoniae and H. influenzae, respectively, had a garenoxacin MIC at ≥2 μg/mL, thus, making this new “respiratory antipneumococcal” quinolone an attractive candidate for the therapy of contemporary CA-RTI (bronchitis, pneumonia, and sinusitis).