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目的:研究异烟肼耐药的结核分枝杆菌中katGS315T突变的发生情况,并探讨katGS315T突变与耐多药结核病(MDR-TB)患病率之间的相关性。设计:收集了从2001年到2004年间所有到大阪市呼吸与过敏性疾病医学中心就诊的新登记病人的临床分离株1 655株,并进行了药物敏感性分析。对1 655株菌株中的1 629株(98.4%)应用插入序列(IS)6110-限制性片段长度多态性(RFLP)法进行了基因分型。对所有耐异烟肼的145个临床分离株,包括耐多药菌株,都进行了katGS315T的突变情况检测。结果:560(34.4%)株临床分离株有相同的RFLP图谱。在145个INH耐药的分离株中,18/48(37.5%)属于有katGS315T突变的RFLP簇,23/97(23.7%)没有发生此突变。在66个耐多药结核病病例中,18/29(62.1%)属于有katGS315T突变的RFLP簇,11/37(29.7%)没有发生此突变。在29例广泛耐药病例(XDR)中,17/21(80.9%)属于有katGS315T突变的RFLP簇,3/8(37.5%)没有发生此突变。结论:发生katGS315T突变的MDR-/XDR-TB分离株中应用IS-RFLP分析获得的成簇率非常高。我们的研究表明katGS315T突变与MDR-TB,尤其是XDR-TB的传播动力学高度相关。
Objective: To investigate the incidence of katGS315T mutation in isoniazid-resistant Mycobacterium tuberculosis and to explore the correlation between katGS315T mutation and the prevalence of multidrug-resistant tuberculosis (MDR-TB). Design: A total of 1 655 clinical isolates from newly registered patients attending the Respiratory and Allergic Diseases Medical Center in Osaka from 2001 to 2004 were collected and analyzed for drug susceptibility. 1 629 (98.4%) of 1 655 strains were genotyped using insertional sequence (IS) 6110-restriction fragment length polymorphism (RFLP). All 145 clinical isolates against isoniazid, including multidrug-resistant strains, were tested for the mutation of katGS315T. Results: 560 (34.4%) strains of clinical isolates had the same RFLP pattern. Out of 145 INH-resistant isolates, 18 of 48 (37.5%) belonged to the RFLP cluster with the katGS315T mutation and 23/97 (23.7%) did not. Of the 66 MDR-TB cases, 18 of 29 (62.1%) belonged to the RFLP cluster with the katGS315T mutation and 11 of 37 (29.7%) did not. Of the 29 cases of extensive drug resistance (XDR), 17 of 21 (80.9%) belonged to the RFLP cluster with the katGS315T mutation and 3 of 8 (37.5%) did not. CONCLUSIONS: The clustering rate obtained using IS-RFLP analysis of MDR- / XDR-TB isolates with the katGS315T mutation is very high. Our study shows that the katGS315T mutation is highly correlated with the transmission kinetics of MDR-TB, especially XDR-TB.