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Antimicrobial Agents and Chemotherapy, November 2003, p. 3542-3547, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3542-3547.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Service de Microbiologie, Hôpital Européen Georges Pompidou,¹ C.N.R. des Pneumocoques, Hôpital Européen Georges Pompidou, 75908 Paris Cedex 15,² L.R.M.A., INSERM E0004 Université Paris VI, 75270 Paris Cedex 06, France³

Received 17 March 2003/ Returned for modification 8 May 2003/ Accepted 21 July 2003

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.

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