江西省利福平及异烟肼耐药结核分枝杆菌的耐药基因分子特征  

Molecular characteristics of resistance genes in rifampicin and isoniazid resistant Mycobacterium tuberculosis in Jiangxi Province

作　　者：赵竟男[1,2] 夏辉[3,4] 江友桥 何旺瑞[1] ZHAO Jing-nan;XIA Hui;JIANG You-qiao;HE Wang-rui(Jiangxi Provincial Center for Disease Control and Prevention,Nanchang,Jiangxi 330029,China;不详)

机构地区：[1]江西省疾病预防控制中心,江西南昌330029 [2]江西省疾病预防控制中心重大疫情防控江西省重点实验室,江西南昌330029 [3]中国疾病预防控制中心结核病预防控制中心,北京102206 [4]中国疾病预防控制中心传染病溯源预警与智能决策全国重点实验室,北京102206

出　　处：《现代预防医学》2024年第13期2460-2465,共6页Modern Preventive Medicine

基　　金：江西省自然科学基金项目(20202BABL206125);江西省卫生健康委科技计划项目(202310071);重大疫情防控江西省重点实验室(2024SSY06021)。

摘　　要：目的分析江西省利福平耐药和异烟肼耐药结核分枝杆菌对常用抗结核药物的耐药率及分子突变特征,为耐药结核病治疗方案的选择提供参考。方法对纳入的经比例法药敏试验检测利福平和/或异烟肼耐药的139株结核分枝杆菌菌株进行全基因组测序,分析这些菌株对于标准化治疗方案中各药物的分子特征及耐药情况。结果131例利福平基因型耐药菌株中,124例(94.66%)同时发生异烟肼耐药相关基因改变。A组药物中70株(53.44%,70/131)氟喹诺酮类药物耐药基因发生改变,1株(0.76%,1/131)利奈唑胺耐药基因突变。B组药物中仅2株(1.53%,2/131)环丝氨酸耐药基因发生突变。C组药物中乙胺丁醇耐药率最高,为59.54%(78/131)。利福平、异烟肼、氟喹诺酮类药物、乙胺丁醇、链霉素、阿米卡星、乙硫异烟胺耐药基因突变类型主要为rpoB_p.Ser450Leu、katG_p.Ser315Thr、gyrA_p.Ala90Val、embB_p.Met306Val、rpsL_p.Lys43Arg、rrs_r.1401a>g、fabG1_c.-15C>T;1例利奈唑胺耐药突变发生在rplC_p.Cys154Arg。吡嗪酰胺耐药突变发生比较分散。结论江西省耐利福平菌株对氟喹诺酮类药物耐药率很高,临床使用该药物前应检测其敏感性,而对于临床无法常规开展药敏试验的药物应开展基于人群的耐药监测。Objective To analyze the resistance rate and molecular characteristics of rifampicin/isoniazid-resistant Mycobacterium tuberculosis isolated in Jiangxi Province and to provide reference for the selection of drugs for composition of treatment regimen.Methods Whole genome sequencing was performed on 139 Mycobacterium tuberculosis strains that were resistant to rifampicin and/or isoniazid by phenotypic drug susceptibility test.The molecular characteristics and resistance to other anti-tuberculosis drugs were analyzed.Results Among 131 genotypic rifampicin-resistant strains,124(94.66%,124/131)occurred isoniazid resistance related genes.For group A drugs,70/131(53.44%)showed molecular changes associated with fluoroquinolone resistance,and 1/131(0.76%)was found mutation in linezolid resistance related gene.Two strains(1.53%,2/131)showed mutations in the cycloserine(group B drug)resistance gene.For group C drugs,the highest resistance rate was observed for ethambutol(59.54%,78/131).The main types of mutations in the resistance genes of rifampicin,isoniazid,fluoroquinolones,ethambutol,streptomycin,amikacin,and ethionimide were rpoB_p.Ser450Leu,katG_p.Ser315Thr,gyrA_p.Ala90Val,embB_p.Met306Val,rpsL_p.Lys43Arg,rrs_r.1401a>g,fabG1_c.-15C>T,respectively.One linazolamide resistant mutation occurred in rplC_p.Cys154Arg.The pyrazinamide resistant mutations was scattered through the gene.Conclusion The resistance rate of fluoroquinolones among rifampicin-resistant strains is high in Jiangxi Province.Susceptibility testing should be conducted before initial of treatment.Population-based resistance surveillance should be carried out for drugs that cannot be routinely tested.

关 键 词：结核 耐药 全基因组测序 

分 类 号：R446.5[医药卫生—诊断学] R52[医药卫生—临床医学]