宁波地区耐多药结核分枝杆菌pncA基因突变特征与吡嗪酰胺耐药相关性研究  

Characterization of pncA gene mutations in multidrug-resistant Mycobacterium tuberculosis isolates and its correlation with drug resistance to pyrazinamide

作　　者：车洋[1] 杨天池[1] 林相[1] 薄丁旖 CHE Yang;YANG Tian-chi;LIN Xiang;BO Ding-yi(Ningbo Municipal Center for Disease Control and Prevention,Ningbo,Zhejiang 315010,China)

机构地区：[1]宁波市疾病预防控制中心,浙江宁波315010

出　　处：《中国卫生检验杂志》2021年第3期267-269,275,共4页Chinese Journal of Health Laboratory Technology

基　　金：宁波市自然科学基金(2019A610385,2019A610386)。

摘　　要：目的探讨宁波地区耐多药MTB的pnc A基因突变特征与吡嗪酰胺(PZA)耐药之间的关系。方法通过宁波地区2015年-2017年耐药监测项目收集筛选了130株耐多药MTB,应用BACTEC MGIT 960系统检测耐多药MTB的PZA耐药性,同时采用PCR DNA直接测序法检测耐多药MTB的pncA基因突变特征。结果 130株耐多药MTB有71株(54.62%,71/130)对PZA耐药,59株(45.38%,59/130)对PZA敏感。初治耐多药58株,PZA耐药24株,PZA耐药率为41.38%(24/58);复治耐多药72株,PZA耐药47株,PZA耐药率为65.28%(47/72),两者差异有统计学意义(χ2=7.402,P <0.05)。130株耐多药MTB中有61株(46.92%,61/130)发生了pncA基因突变。在71株PZA耐药菌株中,pncA基因突变的菌株为59株(83.10%,59/71),在59株PZA敏感菌株中,pncA基因突变的菌株为2株(3.39%,2/59),PZA耐药菌株中的pncA基因突变率高于敏感菌株(χ2=82.203,P <0.05)。pncA基因突变检测PZA耐药的敏感度、特异度和准确度分别为83.10%、96.61%、89.23%。结论宁波地区耐多药MTB对PZA耐药形势较为严峻,pncA基因突变与PZA耐药相关。Objective To understand the association between characteristics of pnc A gene in multidrug-resistant Mycobacterium tuberculosis and its pyrazinamide( PZA) resistance. Methods A total of 130 multi-drug resistant MTB strains were collected and screened through the drug resistance monitoring project in Ningbo area from 2015 to 2017. The PZA resistance of multi-drug resistant MTB was detected by BACTEC MGIT 960 system,and the mutation characteristics of pnc A gene of multi-drug resistant MTB were detected by PCR DNA direct sequencing method. Results Among the 130 strains of multidrug-resistant Mycobacterium tuberculosis isolates,71 were resistant to PZA( 54. 62%,71/130),59 were sensitive to PZA( 45. 38%,59/130). The drug-resistant rates to PZA in re-treated case group( 65. 28%,47/72) were significantly higher than that in new case group( 41. 38%,24/58),with the differences statistically significant( χ2= 7. 402,P < 0. 05). pnc A gene mutation occurred in 61 multidrug-resistant Mycobacterium tuberculosis strains( 46. 92%,61/130). Among the 71 PZA resistant strains,pnc A mutation was detected in 59 strains( 83. 10%,59/71). Among the 59 PZA sensitive strains,pnc A mutation was detected in 2 strains( 3. 39%,2/59). The mutation rate of pnc A was much higher in PZA resistant strains than in PZA sensitive strains( χ2= 82. 203,P < 0. 05). The sensitivity,specificity and accuracy of pnc A mutation test was 83. 10%,96. 61%,89. 23%. Conclusion Multidrug-resistant Mycobacterium tuberculosis clinical isolates are resistant to PZA seriously and PZA resistance is associated with pnc A gene mutation.

关 键 词：吡嗪酰胺 耐多药结核分枝杆菌 突变 耐药 

分 类 号：R446.5[医药卫生—诊断学]