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首页> 外文期刊>Antimicrobial agents and chemotherapy. >In vitro development of resistance to five quinolones and amoxicillin-clavulanate in Streptococcus pneumoniae.
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In vitro development of resistance to five quinolones and amoxicillin-clavulanate in Streptococcus pneumoniae.

机译：在肺炎链球菌中对五个喹诺酮类药物和阿莫西林-克拉维酸盐的耐药性的体外发育。

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摘要

The ability of 50 sequential subcultures in subinhibitory concentrations of ciprofloxacin, levofloxacin, grepafloxacin, sparfloxacin, trovafloxacin, and amoxicillin-clavulanate to select for resistance was studied for six penicillin-susceptible and four penicillin-intermediate pneumococci. Subculturing in ciprofloxacin, grepafloxacin, levofloxacin, and sparfloxacin led to selection of mutants requiring increased MICs for all 10 strains, with MICs rising from (i) 0.5 to 4.0 to (ii) 4.0 to 32.0 microgram/ml after 7 to 12 passages for ciprofloxacin, from (i) 0.06 to 0.25 to (ii) 0.5 to 8.0 microgram/ml after 5 to 23 passages for grepafloxacin, from (i) 0.5 to 1.0 to (ii) 4.0 to 64 microgram/ml after 14 to 49 passages for levofloxacin, and from (i) 0.125 to 0.25 to (ii) 1.0 to 16.0 microgram/ml after 8 to 26 passages for sparfloxacin. Subculturing in trovafloxacin led to increased MICs for eight strains, with MICs rising from (i) 0.06 to 0.125 to (ii) 0.5 to 8.0 microgram/ml after 6 to 28 passages. Subculturing in amoxicillin-clavulanate led to raised MICs for only one strain, with the MIC rising from 0.015 to 0. 125 microgram/ml after 24 passages. Double mutations in both ParC and GyrA led to high-level quinolone resistance when ParC mutations were at S79. Trovafloxacin MICs were 1 to 2 microgram/ml in double mutants with ParC mutations at positions other than S79 (e.g., D83). Mutations in ParE (at D435, R447, and E474) and GyrB (at S405, D406, and D435) were found in four and six mutants, respectively. In the presence of reserpine, 29 mutants had lower ciprofloxacin MICs (2 to 16 times lower), 8 mutants had lower levofloxacin MICs (2 times), and one mutant had a lower trovafloxacin MIC (2 times), suggesting the involvement of an efflux mechanism. In contrast to the case for quinolones, subculturing in the presence of amoxicillin-clavulanate did not select for resistance to this drug.
机译：研究了50种连续亚培养的亚抑菌浓度环丙沙星，左氧氟沙星，格列氟沙星，司巴沙星，曲伐沙星和阿莫西林-克拉维酸对6种易感青霉素和4种中度青霉素肺炎球菌耐药的选择能力。在环丙沙星，格雷帕沙星，左氧氟沙星和司帕沙星中进行亚培养导致选择了所有10个菌株均需要增加MIC的突变体，环丙沙星经过7到12次传代后MIC从（i）0.5至4.0升至（ii）4.0至32.0微克/毫升，氟哌沙星5到23代后从（i）0.06到0.25至（ii）0.5到8.0微克/毫升，左氧氟沙星在14到49代后从（i）0.5到1.0至（ii）4.0到64微克/毫升，以及司帕沙星经过8到26代后从（i）0.125到0.25到（ii）1.0到16.0微克/毫升。在曲伐沙星中传代培养导致8个菌株的MIC升高，经过6至28代后，MIC从（i）0.06升至0.125到（ii）0.5至8.0微克/ ml。在阿莫西林-克拉维酸中的亚培养仅导致一种菌株的MIC升高，在24次传代后MIC从0.015提高到0.125微克/毫升。当ParC突变位于S79时，ParC和GyrA中的双重突变均导致高水平的喹诺酮耐药性。在除S79（例如D83）以外其他位置具有ParC突变的双突变体中，曲伐沙星MICs为1-2微克/毫升。在四个和六个突变体中分别发现了ParE（在D435，R447和E474处）和GyrB（在S405，D406和D435处）突变。在存在利血平的情况下，环丙沙星MIC较低的29个突变体（低2至16倍），左氧氟沙星MIC较低的8个突变体（2倍），曲伐沙星MIC较低的一个突变体（2倍），提示外排涉及机制。与喹诺酮类药物相反，在阿莫西林-克拉维酸存在下传代培养没有选择出对该药的耐药性。

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