Comparative activity of garenoxacin (BMS 284756), a novel desfluoroquinolone, tested against 8,331 isolates from community-acquired respiratory tract infections: North American results from the SENTRY Antimicrobial Surveillance Program (1999–2001)

Abstract

Emerging resistances to orally administered antimicrobials have escalated among bacteria causing community-acquired respiratory infections (CARTI). The spectrum and potency of garenoxacin, (formerly BMS 284756) was assessed against a collection of CARTI isolates from North American medical centers during a longitudinal surveillance study, the SENTRY Antimicrobial Surveillance Program (1999-2001). A total of 8,331 strains of Hemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae were tested by reference methods and compared to numerous other marketed antimicrobials. Nearly all (95.1%) M. catarrhalis were penicillin-resistant, 27.9% of H. influenzae were ampicillin-resistant and 35.0% of S. pneumoniae had MICs at ≥ 0.12 μg/ml for penicillin. Garenoxacin was very active against the three monitored species with MIC 90 values of ≤0.06 μg/ml. Garenoxacin and other quinolones were equally active against the Gram-negative pathogens (except moxifloxacin which was at least twofold less potent versus M. catarrhalis). However, against pneumococci the rank order of potency (MIC 50 in μg/ml) was: gemifloxacin (0.015) > garenoxacin (0.06) > trovafloxacin = moxifloxacin (0.12) > gatifloxacin (0.25) > levofloxacin = ciprofloxacin (1). A trend toward greater resistance worldwide was observed for ciprofloxacin (MIC, ≥ 4 μg/ml), increasing from 1.5% in 1999 to 6.8% in 2001. The highest quinolone resistance rate was observed in North America. Garenoxacin, a new desfluoro(6)quinolone, was documented to be very active in vitro (MIC, ≤2 μg/ml) against > 99.9% of all CARTI isolates in the SENTRY Program. Evolving resistances to other antimicrobial classes or among currently used quinolones appear to position this investigational desfluoro(6)quinolone as a potential treatment option for future clinical use in ambulatory patients.