结核分枝杆菌异烟肼与乙硫异烟胺交叉耐药的相关基因研究  

Study on genes for cross-resistance to isoniazid and ethionamide in Mycobacterium tuberculosis

作　　者：夏强 刘海灿[2] 赵秀芹[2] 万康林[2] 赵丽丽[2] XIA Qiang;LIU Haican;ZHAO Xiuqin;WAN Kanglin;ZHAO Lili(Hangzhou Di'an Medical Laboratory Center,Hangzhou,Zhejiang 310012,China;Chinese Center for Disease Control and Prevention,Beijing 102206,China)

机构地区：[1]迪安医学检验中心,浙江,杭州310012 [2]中国疾病预防控制中心,北京102206

出　　处：《预防医学》2022年第8期836-841,共6页CHINA PREVENTIVE MEDICINE JOURNAL

摘　　要：目的分析结核分枝杆菌异烟肼(INH)和乙硫异烟胺(Eto)交叉耐药及与相关耐药基因突变的关系,为耐多药结核病的临床诊断和治疗提供依据。方法选择126株结核分枝杆菌临床分离株,包括88株耐多药结核分枝杆菌和38株INH与RFP敏感结核分枝杆菌。采用药物敏感性试验检测菌株对INH和Eto耐药情况;采用PCR检测INH和Eto耐药相关基因katG、inhA、ethA、mshA、ndh、oxyR-ahpC间隔区和inhA启动子;以表型耐药为金标准,计算通过突变基因检测INH与Eto交叉耐药菌株的灵敏度、特异度和准确性。结果126株结核分枝杆菌临床分离株中,INH与Eto交叉耐药菌株37株,占29.37%;INH耐药+Eto敏感的菌株51株,占40.48%;INH敏感+Eto耐药菌株4株,占3.17%;INH与Eto敏感菌株34株,占26.98%。41株Eto耐药菌株中,INH耐药37株,占90.24%。检出katG突变64株,突变率为50.79%;oxyR-ahpC间隔区突变4株,突变率为3.17%;inhA突变2株,突变率为1.59%;均为INH耐药。inhA启动子突变11株,突变率为8.73%;ndh突变1株;均为INH与Eto交叉耐药。ethA突变23株,突变率为18.25%;mshA突变40株,突变率为31.75%;在Eto耐药株和敏感株中均检出。inhA启动子检测INH与Eto交叉耐药菌株的灵敏度为29.73%(95%CI:16.44%~47.17%),特异度为100.00%(95%CI:87.36%~100.00%),准确性为63.38%(95%CI:51.76%~73.63%)。结论Eto耐药菌株中INH耐药率较高。inhA启动子突变与结核分枝杆菌对INH和Eto交叉耐药相关,利用inhA启动子区域突变检测INH与Eto交叉耐药具有一定的参考意义。Objective To examine the association between the cross-resistance to ethionamide(Eto)and isoniazid(INH)and mutations of drug resistant genes in Mycobacterium tuberculosis(MTB),so as to provide the evidence for clinical di⁃agnosis and treatment for multidrug-resistant(MDR)tuberculosis.Methods Totally 126 MTB clinical isolates were se⁃lected,including 88 MDR-MTB clinical isolates and 38 INH-and rifampicin(RFP)-sensitive isolates.The resistance to INH and Eto was tested in MTB clinical isolates using the drug susceptibility test,and the mutations in the spacer re⁃gion of INH and Eto resistance-related katG,inhA,ethA,mshA,ndh,spacer region of oxyR-ahpC and inhA promoter were detected using PCR assay.The phenotypic resistance served as a gold standard,and the sensitivity,specificity and accuracy of gene mutation tests were calculated for detection of MTB clinical isolates cross-resistant to INH and Eto.Results Of the 126 MTB clinical isolates,there were 37 isolates cross-resistant to INH and Eto(29.37%),51 isolates with resistance to INH and susceptibility to Eto(40.48%),4 isolates with susceptibility to INH and resistance to Eto(3.17%)and 34 isolates with susceptibility to INH and Eto(26.98%).Among the 41 Eto-resistant MTB clinical isolates,there were 37 isolates with resistance to INH(90.24%).There were 64 MTB clinical isolates detected with katG muta⁃tions(50.79%),4 isolates with mutation in the spacer region of oxyR-ahpC(3.17%),2 isolates with inhA mutations(1.59%),and these isolates were all resistant to INH.There were 11 MTB clinical isolates detected with mutation in the inhA promoter(8.73%)and one isolate with ndh mutation,and all these isolates were cross-resistant to INH and Eto.There were 23 MTB clinical isolates detected with ethA mutations(18.25%)and 40 isolates with mshA mutations(31.75%),in which Eto-susceptible and-resistant isolates were detected.The diagnostic sensitivity,specificity and accu⁃racy of inhA promoter tests for detection of cross-resistance to INH and Eto were 29.73%(95%CI:16.4

关 键 词：结核病 异烟肼 乙硫异烟胺 交叉耐药 

分 类 号：R521[医药卫生—内科学]