耐多药结核分枝杆菌吡嗪酰胺药物敏感性及pnc A突变情况  

Pyrazinamide susceptibility and pncA mutation profiles of multidrugresistant mycobacterium tuberculosis

作　　者：彭小婉[1] 石洁[1] 陈瑞琴 PENG Xiaowan;SHI Jie;CHEN Ruiqin(Henan Provincial Center for Disease Control and Prevention,Zhengzhou 450016,China;Jinshui District Center for Disease Control and Prevention)

机构地区：[1]河南省疾病预防控制中心,河南郑州450016 [2]郑州市金水区疾病预防控制中心

出　　处：《现代疾病预防控制》2023年第7期504-507,共4页MODERN DISEASE CONTROL AND PREVENTION

基　　金：2019年度河南省医学科技攻关计划联合共建项目(LHGJ20190691);2021年度河南省医学科技攻关计划联合共建项目(LHGJ20210138)。

摘　　要：目的通过鉴定耐多药(multidrug-resistant,MDR)结核分枝杆菌中吡嗪酰胺(pyrazinamide,PZA)耐药的表型和基因型特性,为制定合适的治疗方案提供实验室依据。方法采用液体培养对耐多药结核分枝杆菌进行PZA药物敏感性测定。通过测序鉴定pncA的突变情况,并与标准菌株H37Rv的序列进行比较。结果75株耐多药结核菌中,52株(69.33%)为PZA表型耐药菌株。80.76%的准广泛耐药(pre-extensive drug resistant,pre-XDR)菌株、92.31%的广泛耐药(extensive drug resistant,XDR)菌株以及84.61%的对四种一线药物(异烟肼、利福平、乙胺丁醇、链霉素)耐药的菌株发生了PZA耐药。在PZA耐药菌株中45株(45/52,86.53%)的pncA基因发生了突变。在这些MDR菌株共存在40种不同类型的pncA的突变,包括33个点突变和7个插入缺失突变。在这些突变类型中,有17个为新发现位点。结论对四种一线药物全部耐药的菌株,准广泛耐药菌株和广泛耐药菌株的PZA具有较高耐药率。大多数PZA耐药与pncA相关,该突变散在分布且具有多样性。Objective To provide laboratory evidence for the formulation of appropriate treatment by identifying the phenotypic and genotypic characteristics of pyrazinamide(PZA)resistance in multidrug-resistant(MDR)mycobacterium tuberculosis,Methods PZA susceptibility test was conducted for MDR tuberculosis clinical isolates using the liquid culture.The mutations of pncA were determined by sequencing and compared with the sequence of standard strain H37Rv.Results Of the 75 MDR-TB isolates,52(52/75,69.33%)showed phenotypically PZA resistant,and 80.76%of quasi-extensive drug resistant(pre-XDR)strains,92.31%of extensive drug resistant extensive drug resistant,XDR strains and 84.61%of strains resistant to four firstline drugs(isoniazid,rifampicin,ethambutol,streptomycin)developed resistance to PZA.PncA gene mutation occurred in 45(45/52,86.53%)PZA resistant strains.There were 40 different types of pncA mutations in these MDR strains,including 33 point mutations and 7 insertion and deletion mutations.Among these mutation types,17 were newly discovered loci.Conclusions For the four first-line drug resistant strains,the quasi-extensively resistant strains and extensively resistant strains have higher resistance rates.Most PZA resistance is associated with pncA,and the mutations are scattered and diverse.

关 键 词：结核分枝杆菌 耐多药 吡嗪酰胺 pncA基因 

分 类 号：R52[医药卫生—内科学]