In vitro activities of garenoxacin (BMS-284756) against Streptococcus pneumoniae, viridans group streptococci, and Enterococcus faecalis compared to those of six other quinolones
In vitro activities of garenoxacin (BMS-284756) against Streptococcus pneumoniae, viridans group streptococci, and Enterococcus faecalis compared to those of six other quinolones
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DOI：
10.1128/aac.47.11.3542-3547.2003
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发表时间：
2003-11-01
影响因子：
4.9
通讯作者：
Varon, E
中科院分区：
文献类型：
--
作者：
Grohs, P;Houssaye, S;Varon, E
测定了新喹诺酮类抗生素诺氟沙星与其它喹诺酮类抗生素对不同菌株的抗菌活性。肺炎链球菌、草绿色链球菌（VGS）和粪肠球菌。菌株为喹诺酮类药物敏感临床分离株和喹诺酮类药物耐药菌株，其耐药机制明确，来源于临床分离株或S。pneumoniae R6.临床上对喹诺酮类药物敏感的S. pneumoniae、VGS和E.粪肠球菌显示曲诺沙星MIC在0.03 μ g/ml至0.25 μ g/ml的范围内。当ParC喹诺酮耐药决定区（QRDR）中存在一个突变时，加瑞沙星MIC增加2至8倍，当GyrA QRDR中存在一个突变时，增加4倍（S.当ParC和GyrA QRDR中存在两个或三个突变时，其增加8至64倍，当GyrA和ParC QRDR中存在两个突变时，其增加2，048倍（肺炎链球菌）。主动外排增加对S.肺炎和VGS。对于S.在肺炎链球菌中，诺氟沙星的表现与诺氟沙星和司帕沙星相似，受单个gyrA突变的影响大于受单个parC突变的影响。尽管阿曲诺沙星对不同野生型或突变型沙门氏菌菌株的活性通常是阿曲沙星的2 - 4倍。pneumoniae、VGS和E.粪球菌，它的活性比吉非替尼低2 - 4倍。在每种菌株各自MIC的四倍下，在6小时观察到的对S. pneumoniae感染24 h后，S. oralis和E.粪肠杆菌，不受突变的存在下，无论是在ParC或在ParC和GyrA QRDRs。
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 mug/ml to 0.25 mug/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.