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目的了解重庆结核分支杆菌的katG315突变特征,评价其作为诊断异烟肼(Isoniazide,INH)耐药结核杆菌分子标记物的临床应用价值。方法采用DNA测序方法,分析重庆市结核病人痰中分离的97株INH耐药、敏感结核杆菌菌株间的katG基因突变特征,与传统药敏实验进行诊断学试验评价katG315突变作为INH耐药株分子标记物的临床应用价值。结果49株INH耐药结核杆菌中katG315突变率为75.5%,而48株INH敏感结核杆菌中未见katG315突变;INH高度耐药菌株中katG315的突变率为88.5%,显著高于INH低度耐药株的60.9%(P<0.01);耐多药结核杆菌中katG315突变率为89.7%,显著高于单耐INH的结核杆菌的55.0%(P<0.05),耐2种药物及以上药物的结核杆菌中的katG315突变率均显著高于单耐INH菌株(P<0.05);来自复治病例的耐INH菌株中的katG315突变率为95%,显著高于来自初治病例的INH耐药菌株的62.1%(P<0.05);katG315突变诊断INH耐药菌株的诊断学试验评价主要指标为:灵敏度=75.5%;特异度=100%;准确度=87.6%;Youde指数=75.5%。结论katG315突变是重庆地区结核杆菌产生INH耐药性的主要分子机制,且与耐药程度和耐药数量呈显著有关,其作为INH耐药菌株诊断的分子标记物具有良好的临床应用价值。
Objective To understand the katG315 mutation in Mycobacterium tuberculosis in Chongqing and evaluate its clinical value as a molecular marker for the diagnosis of Mycobacterium tuberculosis isolates of Isoniazide (INH). Methods DNA sequencing was used to analyze the mutation of katG gene among 97 strains of INH resistant and susceptible Mycobacterium tuberculosis isolated from sputum of patients with tuberculosis in Chongqing. The katG315 mutation was evaluated as a marker of INH resistant strains by diagnostic tests with traditional drug susceptibility tests The clinical value of the marker. Results The mutation rate of katG315 in 49 strains of INH-resistant Mycobacterium tuberculosis was 75.5%, while no katG315 mutation was found in 48 strains of INH-sensitive Mycobacterium tuberculosis. The mutation rate of katG315 in highly INH-resistant strains was 88.5%, which was significantly higher than that of INH (P <0.01). The mutation rate of katG315 in multidrug-resistant Mycobacterium tuberculosis was 89.7%, which was significantly higher than 55.0% (P <0.05) of single-resistant INH-resistant Mycobacterium tuberculosis. The resistance rates of two drugs and the above drugs The mutation rate of katG315 in Mycobacterium tuberculosis was significantly higher than that of INH isolates (P <0.05). The mutation rate of katG315 in INH resistant strains was 95%, which was significantly higher than that of INH resistant strains from untreated cases (62.1%) (P <0.05). The main diagnostic criteria for the diagnosis of INH-resistant strains by katG315 mutation were sensitivity = 75.5%, specificity = 100%, accuracy = 87.6% and Youde index = 75.5%. Conclusions The katG315 mutation is the major molecular mechanism of INH resistance in Mycobacterium tuberculosis in Chongqing area. It is closely related to the degree of drug resistance and the number of drug resistance. It has good clinical value as a molecular marker for the diagnosis of INH resistant strains.