利福平和异烟肼结核分枝杆菌药敏表型和基因型的关系

The relationship of drug susceptibility phenotype and genotype of Mycobacterium tuberculosis for rifampin and isoniozid

目的对利福平(RFP)和异烟肼(INH)进行药敏检测,分析相应的结核分枝杆菌药敏表型与基因型的关系。方法对2009年至2012年深圳市第三人民医院结核病门诊和住院的137例结核病患者晨痰标本进行结核分枝杆菌培养,利用膜基因芯片法检测结核分枝杆菌耐药基因的突变情况(基因型检测),同时以绝对浓度法进行异烟肼和利福平药敏试验(表型检测),计算两种方法检测结果间的符合率,验证膜基因芯片方法的准确性,用Kappa检验分析两种方法的一致性。结果137株结核分枝杆菌标本,表型检测利福平和异烟肼耐药率分别为27.01%(37/137)和22.63%(31/137);基因型检测利福平和异烟肼耐药率分别为26.28%(36/137)和23.36%(32/137);以绝对浓度法药敏结果为金标准,膜基因芯片检测利福平耐药的敏感度为83.78%(31/37),特异度为94.06%(95/101),符合率为91.97%(126/137),Kappa值为0.79,P<0.05;异烟肼耐药的敏感度为80.65%(25/31),特异度为94.29%(99/105),符合率为90.51%(124/137),Kappa值为0.73,P<0.05;两种药物药敏结果总符合率为91.24%(250/274)。结论结核分枝杆菌耐药性基因型检测和表型检测结果高度一致,且基因型的检测方法能快速准确地检测结核分枝杆菌对利福平和异烟肼的耐药性,有望在临床治疗中广泛应用。

Objective Analysis drug susceptibility phenotype and genotype of Mycobacterium tuberculosis（Mtb） to rifampin（RFP） and isoniozid（INH）.Methods One hundred and thirty-seven morning sputum specimens were cultured for Mycobacterium tuberculosis at Shenzhen Third People＇s Hospital from 2009 to 2012,Use membrane gene chip test technology to detect the mutation type of RFP and INH resistance gene,absolute concentration drug susceptibility test were performed at the same time,calculate the coincidence rate between membrane gene chip test results and the absolute concentration drug susceptibility test,to verify the accuracy of the membrane gene chip method.Results The ratio of phenotype drug-resistant for RFP and INH were 27.01（37/137） and 22.63%（31/137）,the ratio of genotype drug-resistant for RFP and INH were 26.28（36/137） and 23.36%（32/137）.Compared with the gold standard of absolute concentration drug susceptibility test,the membrane gene chip method for RFP displayed the sensitivity 83.78%（31/37）,specificity 94.06%（95/101）,concordance 91.97%（126/137）,the value of Kappa was 0.79,P0.05;INH displayed the sensitivity 80.65%（25/31）,specificity 94.29%（99/105）,concordance 90.51%（124/137）,the value of Kappa was 0.73,P0.05;the total concordances were 91.24%（250/274） for the two drugs.Conclusion The membrane gene chip susceptibility results and absolute concentration method susceptibility results are highly consistent,which is adapted for extensive application in clinical treatment,as it allows fast and accuracy detection of the resistance to RFP and INH in Mtb clinical isolates.