长春地区幽门螺杆菌耐药性和克拉霉素耐药基因突变位点分析  

Drug resistance and clarithromycin resistance gene mutations in Helicobacter pylori strains circulating in Changchun area

作　　者：铁丹丹 赵春燕[1] 范聪聪[1] 江海洋[1] 王丽波[2] Tie Dandan;Zhao Chunyan;Fan Congcong;Jiang Haiyang;Wang Libo(Department of Medical Microbiology and Parasitology,College of Basic Medical Sciences,Jilin University,Changchun 130021,China;Department of Gastroenterology,the First Hospital of Jilin University,Changchun 130021,China)

机构地区：[1]吉林大学基础医学院病原生物学系,130021 [2]吉林大学第一医院胃肠内科,130021

出　　处：《中华微生物学和免疫学杂志》2019年第4期264-269,共6页Chinese Journal of Microbiology and Immunology

基　　金：吉林省科技发展计划资助项目(20170204051SF).

摘　　要：目的探讨幽门螺杆菌对常用抗生素的耐药性及对克拉霉素耐药菌株进行耐药基因突变位点分析,为临床根除幽门螺杆菌选择敏感抗生素以及为患者提供个体化治疗提供参考。方法利用琼脂稀释法检测幽门螺杆菌对常见抗生素的耐药情况,PCR法扩增克拉霉素耐药菌株的23S rRNA基因,测序并对其基因突变位点进行分析。结果本研究成功分离出幽门螺杆菌69株,阳性率为23.1%。对7种常用抗生素的耐药性分析结果显示,幽门螺杆菌对克拉霉素耐药率最高为52.2%,对替硝唑、左氧氟沙星、盐酸四环素、呋喃唑酮和甲硝唑的耐药率依次为47.8%、37.7%、33.3%、30.4%和30.4%,对阿莫西林的耐药率最低为5.8%,可继续作为一线抗菌药物继续使用。在克拉霉素耐药菌株中发现23S rRNA基因有7个突变位点:A1821G、G1826A、T1830C、G1940A、A2143G、T2182C、A2223G。其中A2143G位点突变占54.2%,是本地区幽门螺杆菌分离株对克拉霉素耐药的主要突变位点。结论本地区分离的幽门螺杆菌对克拉霉素的耐药率最高,耐药机制多以23S rRNA基因A2143G位点突变为主。Objective To investigate the resistance of Helicobacter pylori(H.pylori)strains to common antibiotics and to analyze the sites of genetic mutations carried by clarithromycin-resistant strains in order to provide reference for selecting sensitive antibiotics against H.pylori and for providing individualized treatment for patients in Changchun area.Methods Drug resistance of H.pylori clinical isolates to common antibiotics was detected by disk dilution method.The 23S rRNA genes of clarithromycin-resistant strains were amplified by PCR and then sequenced to analyze the presence of mutations.Results In this study,69 strains of H.pylori were successfully isolated with a positive rate of 23.1%.Results of the drug susceptibility test to seven commonly used antibiotics showed that there were 52.2%of the isolates resistant to clarithromycin,47.8%to tinidazole,37.7%to levofloxacin,33.3%to tetracycline hydrochloride,30.4%to furazolidone,30.4%to metronidazole and 5.8%to amoxicillin.Amoxicillin could continue to be used as a first-line antimicrobial agent.Seven mutation sites were found in the 23S rRNA genes carried by the clarithromycin-resistant strains,which were A1821G,G1826A,T1830C,G1940A,A2143G,T2182C and A2223G.The A2143G site mutation accounted for 54.2%and was the predominant mutation resulting in the resistance to clarithromycin of H.pylori strains circulating in this area.Conclusions The H.pylori strains isolated from patients with gastroduodenal diseases in Changchun area had a high resistance rate to clarithromycin,which was mainly caused by the A2143G mutation in 23S rRNA gene.

关 键 词：幽门螺杆菌 克拉霉素耐药性 23S RRNA 基因突变 

分 类 号：R573[医药卫生—消化系统] R446.5[医药卫生—内科学]