北京市昌平区耐多药结核分枝杆菌对新抗结核药品的耐药情况分析  

Analysis of drug resistance of multidrug-resistant Mycobacterium tuberculosis to multiple drugs in Changping District of Beijing

作　　者：刘新宇[1] 张倩[1] 孙倩[1] LIU Xin-yu;ZHANG Qian;SUN Qian(Department of Clinical Laboratory,Beijing Changping Center for Tuberculosis Control,Beijing 102200,China)

机构地区：[1]北京市昌平区结核病防治所检验科,102200

出　　处：《结核与肺部疾病杂志》2021年第2期169-173,共5页Journal of Tuberculosis and Lung Disease

基　　金：首都卫生发展科研专项(2020-1-1041)。

摘　　要：目的探讨北京市昌平区耐多药结核分枝杆菌对左氧氟沙星(levofloxacin,Lfx)、莫西沙星(moxifloxacin,Mfx)、贝达喹啉(bedaquiline,Bdq)、利奈唑胺(linezolid,Lzd)、氯法齐明(clofazimine,Cfz)和德拉马尼(delamanid,Dlm)的耐药特点和耐药突变类型,为临床用药提供依据。方法收集2011—2015年北京市昌平区结核病防治所收治的经分离培养及菌种鉴定后获得的83株耐多药结核分枝杆菌。采用最低药物浓度法对耐多药结核分枝杆菌进行药物敏感性检测,并扩增耐药相关基因序列,将耐药基因测序结果与标准株进行比对分析。结果 83株耐多药结核分枝杆菌菌株对Lfx和Mfx的耐药率最高,均为41.0%(34/83);对Bdq的耐药率最低,为2.4%(2/83),对Lzd、Cfz和Dlm的耐药率分别为4.8%(4/83)、3.6%(3/83)和4.8%(4/83)。39株对Lfx和Mfx耐药的菌株中,gyrA基因第94位密码子的碱基替换是最常见的突变类型,占87.2%(34/39)。2株Cfz-Bdq交叉耐药菌株均在Rv0678基因中存在突变。4株Lzd耐药菌株中有2株存在rplC基因突变。4株Dlm耐药菌株中,1株突变发生在fbiC基因的第318位密码子,2株发生在ddn基因的第81位密码子。结论北京市昌平区耐多药结核分枝杆菌对Lfx或Mfx耐药率较高,对Bdq的耐药率较低;应根据本地区耐多药结核病患者的特点选择耐药率较低的药品。Objective To explore the drug susceptibility of levofloxacin(Lfx),moxifloxacin(Mfx),bedaquiline(Bdq),linezolid(Lzd),clofazimine(Cfz)and delamanid(Dlm)against multidrug-resistant tuberculosis(MDR-TB)isolates from Changping District,and to illustrate the genetic characteristics of MDR-TB isolates with acquired drug resistance,further to provide the basis for clinical drug use,the results of drug resistance gene sequencing were compared with the standard strain. Methods A total of 83 MDR-TB isolates were collected from 2011—2015 in Beijing Changping Center for Tuberculosis Control after culture and strain identification.The minimum inhibitory concentrations(MICs)were used to detect the drug sensitivity of MDR-TB strains,and genes sequence related to drug resistance related genes were amplified and compared with the standard strains. Results Of the 83 MDR-TB isolates,Lfx and Mfx both had the highest resistance rate(41.0%,34/83).The resistance rate to Bdq was the lowest(2.4%,2/83).The resistance rate to Lzd,Cfz,and Dlm was 4.8%(4/83),3.6%(3/83),and 4.8%(4/83),respectively.Among the 39 isolates resistant to Lfx and Mfx,the most prevalent resistance mutation was found in gyrA with the substitution of codon 94(87.2%,34/39).All 2 Cfz-Bdq cross resistant strains had a mutation in the Rv0678 gene,2 of 4 Lzd resistant isolates carried mutations in rplC gene.Of the 4 isolates resistant to Dlm,1 isolate with mutation in codon 318 of fbiC gene and 2 isolates in codon 81 of ddn gene.Conclusion The resistance of MDR-TB isolates to Lfx/Mfx was high while the lowest resistance rate was observed in Bdq in Beijing Changping District.The anti-TB drug with a low resistance rate should be selected according to the characteristics of MDR-TB patients in this region.

关 键 词：分枝杆菌 结核 结核 抗多种药物性 突变 基因 小地区分析 

分 类 号：R52[医药卫生—内科学]