胃癌高发区武威市人群幽门螺杆菌抗生素耐药性分子诊断研究

Molecular diagnosis of Helicobacter pylori antimicrobial resistance in the population of Wuwei City,China,an area with a high incidence of gastric cancer

目的:本研究旨在通过分析幽门螺杆菌(Helicobacter pylori,HP)抗生素耐药性的分子特征,为临床根除HP合理用药提供分子生物学依据。方法:收集2019年2月至2023年11月在甘肃省武威肿瘤医院检查^(14)C呼气试验阳性的1 144例患者的临床资料。采用扩散法药敏实验、耐药基因检测实验、一代测序法进行CYP2C19基因多态性检测,分析HP抗生素耐药性及相关分子生物学特性。结果:在6种抗生素中,甲硝唑的耐药率和耐药基因(rdxA)突变率最高,分别为92.00%和86.12%,阿莫西林的耐药率和耐药基因(Pbp1)突变率最低,分别为11.78%和37.11%;CYP2C19等位基因出现频率快代谢型占46.77%,中等代谢型占44.58%,慢代谢型占8.65%;免疫组织化学发生球形变148例(18.55%)。常规治疗方案用药的HP根除率低于个性化诊疗方案根除率(χ^(2)=8.627,P=0.003);首次接受耐药分子诊断结果治疗方案的根除者根除率要高于复治患者(χ^(2)=6.242,P=0.012)。结论:胃癌高发区武威市人群对阿莫西林抗生素耐药率较低;通过耐药分子生物学诊断结果,可有效提高HP根除率,并为临床合理用药提供参考依据。

Objective:To analyze the molecular characteristics of antibiotic resistance in Helicobacter pylori(HP)and provide a molecular biological basis for clinical eradication of HP by means of rational antibiotic use.Methods:From February 2019 to November 2023,1,144 patients at the Gansu Wuwei Cancer Hospital who tested positive for HP using the ^(14)C-urea breath test were enrolled in the study.Antibiotic resistance and related molecular characteristics of HP,and CYP2C19 polymorphisms in the patients were detected by diffusion drug susceptibility testing,drug resistance gene testing,and next-generation sequencing,respectively.Results:Among the six antibiotics assessed,the resistance rate and the prevalence of resistance genes(rdxA)were highest for metronidazole(92.00%and 86.12%,respectively),and lowest for amoxicillin(Pbp1)(11.78%and 37.11%,respectively).The prevalence of CYP2C19 alleles showed that 46.77%,44.58%,and 8.65%of participants were fast,medium,and slow metabolizers,respectively.Of the participants,148(18.55%)had immunohistochemical sphericity.The eradication rate of HP lower using conventional treatment regimens than that using personalized treatment regimens(χ^(2)=8.627,P=0.003).The HP eradication rate was higher among patients with a first diagnosis of drug resistancebased on molecular testing,than that in patients undergoing retreatment(χ^(2)=6.242,P=0.012).Conclusions:The prevalence of amoxicillin-resistant HP is low in Wuwei City,which has a high incidence of gastric cancer.Molecular diagnosis of antimicrobial resistance could improve the HP eradication rate and provide a reference for rational use of antibiotics in clinical practice.