结核菌耐药pncA和embB基因突变与临床治疗的研究

The Mutation of embB and pncA Genes in Drug-resistanct Mycobacterium Tuberculosis and Its Clinical Value

目的 分别了解结核分枝杆菌耐吡嗪酰胺和乙胺丁醇的pncA和embB基因突变情况 ,研究其治疗对策。方法 通过传统药敏实验和聚合酶链反应 (PCR)一单链构象多态性 (SSCP)技术初步鉴定 10 6株临床分离株的药敏和embB、pncA基因。结果 与结核菌标准株H3 7RV对照分析 94例TB菌耐吡嗪酰胺 (PZA)的pncA基因突变率为 44 69%( 4 2 / 94) ,分析 83例耐乙胺丁醇 (EMB)的embB基因突变率为 5 4 2 %( 4 5 / 83 ) ,两种基因同时突变率为 11 8%( 11/ 94) ,其中embB基因均在传统药敏的高耐药区域。根据上述分析建立的个体化化疗方案治疗 ,痰菌转阴率为 65 9%( 62 / 94) ,病灶治疗有效率为 69 1%( 65 / 94) ,空洞治疗有效率为 5 6 4%( 5 3 / 94)。结论 临床部分结核分枝杆菌耐EMB和PZA是由于其embB、pncA基因突变所致 ,临床根据传统药敏的高、低耐药浓度和基因突变的情况制定的治疗方针 。

Objective To investigate the mutation of embB and pncA genes in mycobacterium tuberculosis isolates, and assess its clinical value. Methods The drug-sensitivity of 106 clinical isolates of mycobacterial species was identified by the tranditional method, and then analyzed the mutation of their embB and pncA genes with PCR-SSCP. Mycobacterium tuberculosis strain H 37 RV was used as a control. Results The mutational frequency of pncA gene in 94 PZA-resistant mycobacterium tuberculosis was 44 6%(42/94). The mutational frequency of embB gene in 83 EMB-resistant isolates was 54 2%. The frequency of both genes mutation was 11 8%(11/94). Conclusion EMB and PZA resistances in some mycobacterium tuberculosis isolates were due to mutations of embB and pncA genes. PCR- SSCP method might become a simple and rapid diagnostic test for genotypes of EMB and PZA resistant mycobacterium tuberculosis.