宁波地区流动人口耐多药肺结核二线抗结核药物耐药状况及耐药基因突变特征分析  

Characterization of second-line anti-tuberculosis drug resistance and gene mutations in multidrug-resistant Mycobacterium tuberculosis among the migratory population in Ningbo

作　　者：车洋[1] 贺天锋[1] 陈同[1] 林律[1] CHE Yang;HE Tian-feng;CHEN Tong;LIN Lu(Nigbo Municipal Center for Disease Control and Prevention,Ningbo 315010,China)

机构地区：[1]宁波市疾病预防控制中心,宁波315010

出　　处：《中国人兽共患病学报》2021年第10期885-892,共8页Chinese Journal of Zoonoses

基　　金：宁波市自然科学基金(No.2019A610385);宁波市医疗卫生品牌学科(No.PPXK2018-10)。

摘　　要：目的了解宁波地区流动人口耐多药肺结核(multidrug-resistant Mycobacterium tuberculosis,MDR-TB)患者临床分离菌株二线抗结核药物耐药状况及耐药基因突变特征。方法以2017-2019年浙江省宁波地区结核病耐药监测收集的133例MDR-TB患者作为研究对象(流动人口占42.11%,56/133;户籍人口占57.89%,77/133),采用1%比例法对患者临床分离菌株进行卡那霉素(kanamycin,KAN)、阿米卡星(amikacin,AMK)、卷曲霉素(capreomycin,CAP)、氧氟沙星(ofloxacin,OFX)、左氧氟沙星(levofloxacin,LVX)5种二线抗结核药物的耐药检测。同时采用PCR DNA直接测序法检测rrs、tlyA、eis、gidB、gyrA、gyrB6个二线抗结核药物耐药相关基因的突变特征。结果56株流动人口MDR-TB患者临床分离菌株KAN耐药率(7.14%,4/56),AMK耐药率(5.36%,3/56),CAP耐药率(1.79%,1/56),OFX耐药率(28.57%,16/56),LVX耐药率(33.93%,19/56)与77株户籍人口患者临床分离菌株KAN耐药率(7.79%,6/77),AMK耐药率(6.49%,5/77),CAP耐药率(3.90%,3/77),OFX耐药率(31.37%,24/77),LVX耐药率(25.97%,20/77)比较差异无统计学意义(χ^(2)_(KAN)=0.020,P=0.888;χ^(2)_(AMK)=0.074,P=0.786;χ^(2)_(CAP)=0.036,P=0.850;χ^(2)_(OFX)=0.104,P=0.747;χ^(2)_(XLV)=0.990,P=0.320)。56株流动人口MDR-TB患者临床分离菌株准广泛耐药率(Pre-XDR)(33.93%,19/56),广泛耐药率(XDR-TB)(3.57%,2/56)与77株户籍人口患者临床分离菌株准广泛耐药率(Pre-XDR)(24.68%,19/77),广泛耐药率(XDR-TB)(7.79%,6/77)比较差异无统计学意义(χ^(2)_(Pre-XDR)=1.360,P=0.243;χ^(2)_(XDR-TB)=0.411,P=0.521)。56株流动人口MDR-TB患者临床分离菌株rrs突变率(8.93%,5/56)、tlyA突变率(1.79%,1/56)、eis突变率(3.57%,2/56)、gidB突变率(5.36%,3/56)、gyrA突变率(39.29%,22/56)和gyrB突变率(3.57%,2/56)与77例户籍人口患者临床分离菌株rrs突变率(5.19%,4/77)、tlyA突变率(11.69%,9/77)、eis突变率(0.00%,0/77)、gidB突变率(2.60%,2/77)、gyrA突变率(31.17%,24/77)和gyrB突变率(2.60%,2/77)比较差异无This study aimed to characterize the second-line anti-tuberculosis drug resistance and gene mutations of multidrug-resistant Mycobacterium tuberculosis among migratory populations in Ningbo.A total of 133MDR isolates selected in the first drug resistance survey in Ningbo between 2017and 2019were examined in the study.Of 133 MDR patients,56patients from migratory populations were included.Gene sequencing was conducted to detect mutations in the rrs,tlyA,eis,gidB,gyrA and gyrB genes.The conventional drug susceptibility test was used to detect drug-resistance profiles against five second-line antibiotics(kanamycin,amikacin,capreomycin,ofloxacin and levofloxacin).The drug resistance rates of kanamycin,amikacin,capreomycin,ofloxacin and levofloxacin in the migratory population were 7.14%(4/56),5.36%(3/56),=0.05。1.79%(1/56),28.57%(16/56)and 33.93%(19/56),respectively.The rates of pre-XDR and XDR in the migratory population were 33.93%(19/56)and 3.57%(2/56),respectively.The gene mutation rates of rrs,tlyA,eis,gidB,gyrA and gyrBin the migratory population were 8.93%(5/56),1.79%(1/56),3.57%(2/56),5.36%(3/56),39.29%(22/56)and3.57%(2/56),respectively.There was no significant difference in second-line anti-tuberculosis drug resistance between the migratory population group and the resident population group(χ^(2)_(KAN)=0.020,P=0.888;χ^(2)_(AMK)=0.074,P=0.786;χ^(2)_(CAP)=0.036,P=0.850;χ^(2)_(OFX)=0.104,P=0.747;χ^(2)_(XLV)=0.990,P=0.320).There was no significant difference in the rates of pre-XDR and XDR between the migratory population group and resident population group(χ^(2)_(Pre-XDR)=1.360,P=0.243;χ^(2)_(XDR-TB)=0.411,P=0.521).There was also no significant difference in the rates of gene mutation between the migratory population group and resident population group(χ^(2)_(rrs)=0.247、χ^(2)_(tlyA)=3.259、χ^(2)_(eis)=0.901、χ^(2)_(gidB)=0.133、χ^(2)_(gyrA)=0.944、χ^(2)_(gyrB)=0.000,P>0.05).The mutation types of rrs,tlyA,eis,gidB,gyrAand gyrB were 2,1,2,2,5and 4,respectively.Single base substitution was the

关 键 词：流动人口 耐药 细菌 结核分枝杆菌 基因突变 

分 类 号：R372[医药卫生—病原生物学]