【摘要】 目的 研究根除治疗失败患者幽门螺杆菌（Helicobater pylori,Hp）的耐药表型、耐药基因和毒力基因，为补救治疗提供参考依据。方法 采集根除治疗失败患者胃黏膜组织分离培养Hp，药敏实验检测分离菌株对甲硝唑（metronidazole, MTZ）、克拉霉素（clarithromycin, CLA）、左氧氟沙星（levofloxacin, LEV）、阿莫西林（amoxicillin, AMX）、四环素（tetracycline, TET）和呋喃唑酮（furazolidone, FZ）的耐药情况，PCR扩增CLA、LEV耐药基因23S r RNA、gyr A及毒力基因cag A、vac A、ice A、oip A，进一步探究耐药表型与耐药及毒力基因的关系。结果 从58例患者中分离获得40株Hp(69.0%)，其对MTZ、CLA、LEV、AMX、TET、FZ的耐药率分别为100.0%、82.5%、72.5%、0%、0%、0%。23S r RNA、gyr A基因最常见的突变位点分别为T2182C(78.6%)和N87K(32.0%)，并在CLA耐菌株中新发现了C2165T和A2219G突变。此外，这些菌株毒力基因cag A、vac A s1、vac A s2、vac A m1、vac A m2、ice A1、ice A2、oip A的阳性率分别为97.1%、100.0%、0%、42.9%、57.1%、62.9%、11.4%、68.6%,LEV耐药菌株中vac A m2基因阳性率更高，差异具有统计学意义（P<0.05）。结论本地区根除治疗失败患者Hp分离株对MTZ、CLA、LEV的耐药情况严峻，补救治疗推荐选用AMX、TET、FZ。CLA耐药与C2165T和A2219G突变及LEV耐药与vac A m2的关系值得进一步探讨。更多还原

【Abstract】 Objective To study the drug resistance phenotype, drug resistance gene, and virulence gene of Helicobacter pylori(Hp) in patients with failed eradication therapy, and to provide reference for remedial therapy. Methods Hp was isolated and cultured from gastric mucosa of patients with failed eradication therapy. Drug sensitivity test was used to detect the resistance of isolated strains to Metronidazole(MTZ), Clarithromycin(CLA), Levofloxacin(LEV), Amoxicillin(AMX), Tetracycline(TET),and Furazolidone(FZ). CLA and LEV resistance genes 23S r RNA, gyr A and virulence genes cagA, vacA, iceA, oipA were amplified by PCR, to further explore the relationship between drug resistance phenotype and drug resistance and virulence genes. Results In total 40 strains of Hp were isolated from 58 patients(69.0%). The resistance rates to MTZ, CLA, LEV,AMX, TET, and FZ were 100.0%, 82.5%, 72.5%, 0%, 0%, and 0%, respectively. The most common mutations of 23S r RNA and gyrA genes were T2182C(78.6%) and N87K(32.0%), respectively, and new C2165T and A2219G mutations were found in CLA resistant strains. In addition, the positive rates of virulence genes cag A, vac A s1, vacA s2, vac A m1, vac A m2, ice A1,ice A2, and oip A were 97.1%, 100.0%, 0%, 42.9%, 57.1%, 62.9%, 11.4%, and 68.6%, respectively, and the difference was statistically significant. Conclusion The resistance of Hp isolates to MTZ, CLA and LEV in patients with failed eradication therapy in this area is serious, and AMX, TET and FZ are recommended for remedial therapy. The relationship between CLA resistance and C2165T and A2219G mutation and LEV resistance and vacA m2 warrants further investigation.更多还原