Update on fluoroquinolone resistance in Helicobacter pylori:: new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility
Update on fluoroquinolone resistance in Helicobacter pylori:: new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility
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DOI：
10.1016/j.ijantimicag.2006.11.007
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发表时间：
2007-04-01
影响因子：
10.8
通讯作者：
Cambau, Emmanuelle
中科院分区：
文献类型：
--
作者：
Cattoir, Vincent;Nectoux, Juliette;Cambau, Emmanuelle
由于克拉霉素和甲硝唑耐药，标准疗法根除幽门螺杆菌的效果正在下降。氟喹诺酮类药物是有价值的替代治疗药物，但其活性需要更新。我们测定了新上市的氟喹诺酮类药物（左氧氟沙星、阿替沙星和加替沙星）的最低抑菌浓度（MIC），并评估了128例H. 2004-2005年分离的幽门螺杆菌菌株。对所有菌株gyrA的喹诺酮类耐药决定区（QRDR）进行测序。加替沙星的MIC（MIC 50 = 0.25 mg/L）比其他氟喹诺酮类药物低2 - 4倍。耐药率（MIC > 1 mg/L）为17.2%（22株）。所有耐药株均在密码子86、87和91处发生gyrA突变，其中包括3个新突变（Asp 86 Asn、Thr 87 Ile和Asn 87 Tyr）。环丙沙星敏感菌株没有这种gyrA突变，但在密码子87处具有多态性，该多态性将18株（17%）具有Thr 87（如参考菌株J 99）的菌株与88株具有Asn 87（如参考菌株26695）的菌株区分开来。Thr 87的菌株对萘啶酸、培氟沙星、环丙沙星和左氧氟沙星的敏感性增加了4倍，对阿托沙星和加替沙星的敏感性相同。H.幽门螺杆菌需要使用/暗示可以自信地依赖于QRDR gyrA测序的“测试和治疗”策略。(c)2006年Elsevier B. V.和国际化疗学会。All rights reserved.
Helicobacterpylori eradication by standard therapy is decreasing due to clarithromycin and metronidazole resistance. Fluoroquinolones are valuable drugs for alternative therapy, but their activity needs to be updated. We determined minimum inhibitory concentrations (MICs) of the newly marketed fluoroquinolones (levofloxacin, moxifloxacin and gatifloxacin) and assessed the prevalence of resistance in 128 H. C pylori strains isolated in 2004-2005. The quinolone resistance-determining region (QRDR) of gyrA was sequenced for all strains. Gatifloxacin MICs (MIC50 = 0.25 mg/L) were two- to four-fold lower than those of the other fluoroquinolones. The prevalence of resistance (ciprofloxacin MIC > 1 mg/L) was 17.2% (22 strains). All resistant strains harboured one gyrA mutation at codons 86, 87 or 9 1, including three new mutations (Asp86Asn, Thr87Ile and Asn87Tyr). Ciprofloxacin-susceptible strains were devoid of such gyrA mutations, but harboured a polymorphism at codon 87 that distinguished 18 isolates (17%) with a Thr87 like the reference strain J99 from 88 strains with Asn87 like the reference strain 26695. Strains with Thr87 were four-fold more susceptible to nalidixic acid, pefloxacin, ciprofloxacin and levofloxacin and were equally susceptible to moxifloxacin and gatifloxacin. The high rate of quinolone resistance in H. pylori requires the use/implication of a 'test and treat' strategy that can confidently rely on QRDR gyrA sequencing. (c) 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.