125株耐多药结核分枝杆菌的吡嗪酰胺耐药及pncA基因突变分析  

Analysis of pyrazinamide resistance and pncA mutation in 125 multidrug-resistant Mycobacterium tuberculosis isolates

作　　者：赵永[1] 林淑芳[1] 林建[1] 戴志松[1] 魏淑贞[1] ZHAO Yong;LIN Shu-fang;LIN Jian;DAI Zhi-song;WEI Shu-zhen(Fujian Provincial Key Laboratory of Zoonosis Research,Fujian Center for Disease Control and Prevention,Fuzhou 350001,China)

机构地区：[1]福建省疾病预防控制中心/福建省人兽共患病重点研究实验室,福州350001

出　　处：《中国防痨杂志》2021年第10期1079-1083,共5页Chinese Journal of Antituberculosis

基　　金：福建省卫生健康科技计划项目(2019-ZQN-28)。

摘　　要：目的了解125株耐多药结核分枝杆菌对吡嗪酰胺(PZA)的耐药水平和pncA基因的突变特征,为PZA耐药的快速诊断提供依据。方法通过简单随机抽样方法选取2010—2019年福建省9个耐药监测点的125株耐多药菌株,采用BACTEC MGIT 960液体培养进行PZA药物敏感性试验(简称"药敏试验"),通过PCR扩增pncA目的基因,分析耐多药菌株对PZA的耐药性及pncA基因突变情况。结果 50株耐多药菌株对PZA耐药,PZA耐药率为40.0%(50/125)。男性患者PZA耐药率为39.0%(37/95),女性患者PZA耐药率为43.3%(13/30),差异无统计学意义(χ^(2)=0.183,P=0.669);15~25岁、26~45岁、46~60岁、61~80岁患者PZA耐药率分别为58.3%(7/12)、32.7%(16/49)、39.5%(17/43)、47.6%(10/21),PZA耐药率在年龄组之间的差异无统计学意义(χ^(2)=3.294,P=0.348);初治患者PZA耐药率为41.5%(21/65),复治患者PZA耐药率为38.3%(23/60),差异无统计学意义(χ^(2)=0.134,P=0.715)。30株PZA耐药菌株检出pncA基因突变,突变类型22种,突变检出率为60.0%(30/50);PZA耐药株的pncA基因突变检出率[60.0%(30/50)]高于PZA敏感株的pncA基因突变检出率[5.3%(4/75)],差异有统计学意义(χ^(2)=45.276,P=0.000)。结论福建省耐多药结核分枝杆菌的PZA耐药率较高,且pncA基因突变检出率较高,临床上应关注PZA的耐药问题。Objective To investigate the pyrazinamide(PZA)resistance of 125 multidrug-resistant(MDR Mycobacterium tuberculosis isolates and the characteristics of mutation in pncA gene,to provide references for the rapid diagnosis of PZA resistance. Methods A total of 125 MDR strains were simple randomly selected from9 drug-resistant surveillance sites in Fujian,2010—2019.The PZA susceptibility was tested using the MGIT 960 system,and the pncAtarget gene was amplified by PCR to analyze the resistance of MDR strains to PZA and the mutation of pncAgene. Results A total of 50 MDR strains were resistant to PZA,and the PZA resistance rate was 40.0%(50/125).There was no statistical difference of the PZA resistance rate between the male(39.0%(37/95))and the female(43.3%(13/30);χ^(2)=0.183,P=0.669).The PZA resistant rates in the age-group of15-25,26-45,46-60 and 61-80 years were 58.3%(7/12),32.7%(16/49),39.5%(17/43)and 47.6%(10/21),respectively,the difference was no statistically significant (χ^(2)=3.294,P=0.348).There was no statistical difference of the PZA resistance rates between the new cases(41.5%(21/65))and the retreatment cases(38.3%(23/60);χ^(2)=0.134,P=0.715).The mutation of pncAgene was found in 30 PZA resistant MDR strains,and the types of mutations was 22.The mutation rate of pncA gene in PZA resistant MDR strain was 60.0%(30/50),which was significantly higher than that of the PZA sensitive strains(5.3%(4/75),χ^(2)=45.276,P=0.000). Conclusion The PZA resistance rate of MDR Mycobacterium tuberculosis is high in Fujian,and the mutation of pncAgene is also high,attention should be paid to the drug resistance of PZA in clinic.

关 键 词：分枝杆菌 结核 吡嗪酰胺 抗药性 基因突变 

分 类 号：R446.5[医药卫生—诊断学]