耐多药结核分枝杆菌对阿米卡星耐药与rrs基因突变的相关性研究  

Correlation between amikacin resistance and rrs gene mutation in multidrug-resistant Mycobacterium tuberculosis

作　　者：任振娟 张海杰 苏云开 马岩 刘耀 REN Zhen-juan;ZHANG Hai-jie;SU Yun-kai;MA Yan;LIU Yao(Reference Laboratory of the Fourth Hospital of Inner Mongolia Autonomous Region,Hohhot010080,China)

机构地区：[1]内蒙古自治区第四医院参比实验室,呼和浩特010080

出　　处：《结核与肺部疾病杂志》2020年第3期117-120,共4页Journal of Tuberculosis and Lung Disease

摘　　要：目的分析耐多药结核分枝杆菌(MDR-MTB)对阿米卡星(Am)耐药与rrs基因突变的相关性。方法选取2005年和2015年内蒙古自治区第四医院参比实验室的共计159株MDR-MTB临床分离株,用绝对浓度法检测其对Am的耐药率,同时对Am耐药菌株进行rrs基因测序,再用微孔板阿尔玛蓝试验(MABA)测定药品的体外最低抑菌浓度(MIC)值,并以绝对浓度法检测结果作为标准,绘制MIC值诊断菌株Am耐药的受试者工作特征曲线(ROC曲线)。结果 2005年分离的MDR-MTB菌株中对Am耐药者有18株(24.0%,18/75),2015年分离的MDR-MTB菌株中有27株(32.1%,27/84)对Am耐药。对Am耐药的MDR-MTB菌株中有44株(97.8%,44/45)发生A1401G突变,其中有10株(22.2%)同时发生T1384A突变。ROC曲线分析显示,Am耐药判断界值(cut-off值)为1.5μg/ml,对应的敏感度为91.1%,特异度为98.2%。结论 MDR-MTB菌株rrs基因A1401G和T1384A突变与其对Am耐药相关,MIC值1.5μg/ml可用于区分其对Am的敏感性和耐药性。Objective To analyze the correlation between Amikacin(Am)resistance and rrs gene mutation in multidrug-resistant Mycobacterium tuberculosis(MDR-MTB).Methods A total of 159 MDR-MTB clinical isolates were selected from the reference laboratory of the Fourth Hospital of Inner Mongolia Autonomous Region in year2005 and 2015.The absolute concentration method was used to detect the drug resistance rate to Am.At the same time,the rrs gene of Am resistant strains was sequenced,and the minimum inhibitory concentration(MIC)in vitro was determined by microplate Alamar Blue assay(MABA).Based on results of test using the absolute concentration method,receiver operating characteristic curve(ROC curve)of MIC value for diagnosis of the drug resistance of Am was made.Results Among the MDR-MTB strains isolated in 2005,18(24.0%,18/75)were resistant to Am,as to those in 2015,the proportion was 27(32.1%,27/84).Of the Am resistant MDR-MTB strains,44(97.8%)had A1401 Gmutation and 10(22.2%)had T1384 A mutation.Analysis of ROC curve showed that the cut-off value of Am was 1.5μg/ml,the corresponding sensitivity was 91.1%,and the corresponding specificity was 98.2%.Conclusion A1401 Gand T1384 Amutations in rrs gene of MDR-MTB strains were associated with Am resistance.The MIC value of 1.5μg/ml could be used to distinguish the sensitivity and resistance of MDR-MTB strains to Am.

关 键 词：分枝杆菌 结核 结核 抗多种药物性 丁胺卡那霉素 微生物敏感性试验 基因 突变 

分 类 号：R52[医药卫生—内科学] R446.5[医药卫生—临床医学]