In vitro activities of garenoxacin (BMS-284756) against Streptococcus pneumoniae, viridans group streptococci, and Enterococcus faecalis compared to those of six other quinolones.
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 microg/ml to 0.25 micro g/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.
Service de Microbiologie, Hôpital Européen Georges Pompidou, 75908 Paris Cedex 15, France.
Patrick
P
Grohs
Serge
S
Houssaye
Agnès
A
Aubert
Laurent
L
Gutmann
Emmanuelle
E
Varon
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial; D013293:Enterococcus faecalis / Q000187:drug effects*; D024841:Fluoroquinolones / Q000494:pharmacology*; D005798:Genes, Bacterial / Q000235:genetics; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000494:pharmacology*; D019533:Streptococcus oralis / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D034363:Viridans Streptococci / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D015363:Quinolones; C419689:garenoxacin