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.
Grohs
Patrick
P
Service de Microbiologie, Hôpital Européen Georges Pompidou, 75908 Paris Cedex 15, France.
Houssaye
Serge
S
Aubert
Agnès
A
Gutmann
Laurent
L
Varon
Emmanuelle
E
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