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中国防痨杂志 ›› 2005, Vol. 27 ›› Issue (4): 229-232.

• 论著 • 上一篇    下一篇

耐多药肺结核耐药基因突变与临床疗效探讨

林明贵;李洪敏;吴雪琼;金关甫;王巍;王安生;张韬;丹子军;李燕峰;   

  1. 解放军309医院 北京 100091;
  • 出版日期:2005-04-10 发布日期:2005-11-03

The research on the relationship between the therapeutic effect and the mutations of the drug-resistant genes in multi-drug resistant pulmonary tuberculosis

Lin Minggui, Li Hongmin, Wu Xueqiong, et al.   

  1. The 309 Hospital of PLA, Beijing 100091,Chin
  • Online:2005-04-10 Published:2005-11-03

摘要: 目的 了解耐多药肺结核耐药基因的突变与临床疗效的关系,为耐多药肺结核的治疗提供参考依据。方法 108例病人痰标本用PCR-SSCP方法检测了五种耐药基因和传统的药敏试验,并与临床疗效进行比较分析。结果 耐多药肺结核耐药基因检测率分别是耐异烟肼的katG基因突变率为70.4%,耐利福平的rpoB基因突变率72.2%,耐链霉素的rpsL基因突变率71.9%,耐吡嗪酰胺的pncA基因突变率53.4%,耐乙胺丁醇的embB基因突变率31.7%,其中高浓度耐药菌的基因突变率远高于低浓度的突变率。根据药敏试验及耐药基因检测结果指导治疗,应用以KAOP为基础的化疗方案,配合患者过去未曾用过的1~2种抗结核药物,经过平均1.4年的治疗,108例耐多药病人74.1%的病人痰菌阴转,且67.5%的病人痰结核杆菌培养阴转,83.3%的病人病灶吸收好转,65.3%的空洞闭合,取得了临床上较为满意的疗效。结论 对耐多药肺结核进行耐药基因检测是一项重要工作,对指导治疗及预后判断有一定的参考价值。但尚需进行更多的观察。

关键词: 抗药性,多药, 分枝杆菌,结核, 聚合酶链反应-单链构象多态性, 基因突变, 治疗

Abstract: Objective To investigate the relationship between the therapeutic effect and the mutations of the drug-resistant genes in multi-drug resistant pulmonary tuberculosis, and to provide the theoretical evidence for treating the multi-drug resistant pulmonary tuberculosis. Methods108 M. tuberculosis clinical isolates from sputum specimens were detected by PCR-SSCP and the traditional drug susceptibility testing. The therapeutic effect of the patients with multi-drug resistant tuberculosis was evaluated. ResultsThe rates of mutations of katG gene for Isoniazid resistance, rpoB gene for Rifampin resistance, rpsL gene for Streptomycin resistance, pncA gene for Pyrizinaride resistance and embB gene for Ethambutol resistance were 70.4%, 72.2%, 71.9%, 53.4% and 31.7%, respectively. The rate of gene mutation was higher in the isolate with high concentration of drug resistance than that with low concentration of drug resistance. According to the Results of PCR-SSCP and drug susceptibility testing, the patients were treated with 1 to 2 kinds of anti-TB drugs never used before combined with a regimen of KAOP (kanamycin, ofloxacin, sodium aminosalicylate) for average 1.4 years. The sputum bacterial negative conversion rate was 74.1%, the sputum culture-negative conversion rate was 67.5%, the absorption rate of lesion was 83.3%, 65.3% of the cavities closed up. There wasn’t any serious side effect to be found. ConclusionThe detection of drug-resistant genes might be helpful for the clinical treatment of multi-drug resistant pulmonary tuberculosis.

Key words: Multi-drug resistance, M.toberculosis, PCR-SSCP,gene mutation, therapy