In Vitro Activities of Garenoxacin (BMS-284756) against Streptococcus pneumoniae , Viridans Group Streptococci, and Enterococcus faecalis Compared to Those of Six Other Quinolones

Abstract

ABSTRACT The activity of garenoxacin, a new quinolone, was determined in comparison with other quinolones against different strains of S. pneumoniae , viridans group streptococci (VGS), and Enterococcus faecalis . Strains were quinolone-susceptible clinical isolates and quinolone-resistant strains with defined mechanisms of resistance obtained from either clinical isolates or derivatives of S. pneumoniae R6. Clinical quinolone-susceptible strains of S. pneumoniae , VGS and E. faecalis showed garenoxacin MICs within a range of 0.03 μg/ml to 0.25 μg/ml. Garenoxacin MICs increased two- to eightfold when one mutation was present in the ParC quinolone resistance-determining region (QRDR), fourfold when one mutation was present in the GyrA QRDR ( S. pneumoniae ), 8- to 64-fold when two or three mutations were associated in ParC and GyrA QRDR, and 2,048-fold when two mutations were present in both the GyrA and ParC QRDRs ( Streptococcus pneumoniae ). Increased active efflux had a moderate effect on garenoxacin MICs for S. pneumoniae and VGS. Against S. pneumoniae , garenoxacin behaved like moxifloxacin and sparfloxacin, being more affected by a single gyrA mutation than by a single parC mutation. Although garenoxacin was generally two- to fourfold more active than moxifloxacin against the different wild-type or mutant strains of S. pneumoniae , VGS, and E. faecalis , it was two- to fourfold less active than gemifloxacin. At four times the respective MIC for each strain, the bactericidal effect of garenoxacin, observed at 6 h for S. pneumoniae and at 24 h for S. oralis and E. faecalis , was not influenced by the presence of mutation either in the ParC or in both the ParC and GyrA QRDRs.