摘要目的 了解重庆结核杆菌的embB306突变特征,评价其作为诊断乙胺丁醇(ethambutol,EMB)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患者痰中分离的51株EMB耐药结核杆菌和50株EMB敏感株的embB基因突变特征,与传统药敏实验进行诊断学试验评价embB306突变作为EMB耐药株分子标记物的临床应用价值.结果 embB306突变率在51株EMB耐药和50株敏感结核杆菌中分别为75.5%、6%;其中来自复治病例的EMB耐药菌株的embB306突变率是87.5%,高于来自初治病例的48.1%;embB306突变率随菌株耐药数量增加而升高,embB306在EMB耐药的耐多药菌株(Multidrug-Resistant Tuberculosis,MDR-TB)中的突变率高于EMB耐药的非MDR-TB和EMB敏感的MDR-TB的突变率;以embB306突变诊断EMB耐药菌株的诊断学试验评价主要指标为:灵敏度为66.7%;特异度为94.0%;准确度为80.2%;Youden指数为60.7%.结论embB306突变是重庆地区结核杆菌产生EMB耐药性的主要分子机制,且与耐药数量和治疗时间有关,其作为EMB耐药菌株诊断的分子标记物具有一定临床应用价值.

abstractsObjective To understand the characteristics of embB gene mutation of Mycobacterium tuberculosis (MTB) isolates from tuberculosis patients in Choagqing, and the value of embB306 as a molecular marker used to diagnose ethambutol (EMB)-resistant MTB strains. Methods Direct sequencing was used to analyze the polymorphism of embB mutation in 51 EMB-resistant MTB strains and 50 EMB-sensitive MTB strains. And diagnostic testing was used to evaluate the value of embB306 as a molecular marker of EMB -resistant MTB strains as compared with the traditional sensitivity test. Results All 34 of 51 EMB-resistant strains (66.7%) and 3 of 51 EMB- sensitive strains (6%) had had embB306 mutation. The embB306 mutation rate in EMB-resistant strains coming from previously treated case was 87.5%, showing significantly higher than that from new cases (48.1% ,P<0.01); embB306 mutation rate was increased with the number of the resistant drugs; embB306 mutation serving as a marker to diagnose EMB-resistant MTB strains comparing with the traditional sensitivity test,had the rate of sensitivity = 66.7% ,specificity =94.0% ,accuracy = 80.2% and Youden index = 60.7%. Conclusion embB306 mutation should be the main mechanism of MTB resistance to EMB in Chongqing, showing an association with the history of the treated and numbers of the resistant drugs, embB306 mutation should be a good marker to diagnose EMB-resistant MTB strains.