基因芯片法在结核分枝杆菌耐药基因快速诊断中的应用价值

目的 探讨基因芯片法在结核分枝杆菌耐药基因快速诊断中的应用价值。 方法 收集2017年6月至2018年6月厦门大学附属第一医院肺科门诊及住院的933例疑似肺结核患者初诊时采集的同一份晨痰标本,同时进行基因芯片法、GeneXpert MTB/RIF(简称“GeneXpert”)和BACTEC MGIT 960液体培养及其比例法药物敏感性试验(简称“MGIT 960及其比例法药敏试验”)3种方法进行结核分枝杆菌及其耐药性检测,对检测结果进行对比分析。 结果 933例患者的痰标本中,基因芯片法检测出阳性484例,GeneXpert检测出阳性462例,MGIT 960培养出阳性411例。三种检测方法均为阳性的标本有395例,采用Excel表通过完全随机的方式抽取232例进行耐药性检测,以比例法药敏试验结果为参考标准,基因芯片法检测出异烟肼耐药的敏感度为86.67%(26/30),特异度为96.53%(195/202),一致性为95.26%(221/232),Kappa值为0.798(0.682~0.914);检测出利福平耐药的敏感度为93.75%(30/32),特异度为97.00%(194/200),一致性为96.55%(224/232),Kappa值为0.862(0.768~0.956);GeneXpert检测出利福平耐药的敏感度为84.38%(27/32),特异度为97.00%(194/200),一致性为95.26%(221/232),Kappa值为0.803(0.691~0.915);基因芯片法与GeneXpert对利福平耐药检测的一致性为96.12%(223/232),Kappa值为0.847(0.749~0.945)。Kappa值均大于0.75,具有良好的一致性。 结论 以MGIT 960及其比例法药敏试验结果为标准,基因芯片法敏感度、特异度和一致性高,与GeneXpert也具有良好的一致性,有助于结核病的早期诊断及防控。

Evaluation of gene chips for the rapid diagnosis of drug-resistance genes in Mycobacterium tuberculosis

Objective To evaluate the performance of gene chips in the detection of Mycobacterium tuberculosis (MTB) and determination of drug resistance. Methods Morning sputum specimens were collected from 933 suspected pulmonary tuberculosis patients at the First Affiliated Hospital of Xiamen University from June 2017 to June 2018. The sensitivity and specificity of gene chips was compared with that of GeneXpert MTB/RIF (GeneXpert) and BACTEC MGIT 960 liquid culture, and the Roche proportional drug sensitivity testing method (MGIT 960 culture+proportional method DST). Results Of 933 cases of sputum specimens, 484 sputum specimens were determined to be MTB positive using gene chips, 462 were detected as positive using GeneXpert, and 411 were detected as positive using MGIT 960. Three hundred and ninety-five samples were detected as MTB positive by all three methods, 232 cases were then selected randomly for evaluation of drug resistance, results from the Roche proportion method being used as a reference standard. For isoniazid resistance, gene chips had a sensitivity of 86.67% (26/30), and a specificity of 96.53% (195/202). Their consistency with the Roche proportion method was 95.26% (221/232), with a Kappa value of 0.798 (0.682-0.914). For rifampicin resistance, the sensitivity of gene chips was 93.75% (3032), specificity was 97.00% (194/200), consistency was 96.55% (224/232), and the Kappa value was 0.862 (0.768-0.956). For GeneXpert, the sensitivity of rifampicin resistance was 84.38% (27/32), specificity was 97.00% (194/200), consistency was 95.26% (221/232), and the Kappa value was 0.803 (0.691-0.915). The Kappa values obtained were all higher than 0.75 indicating that all three methods had good consistency. Conclusion We did not detect any significant difference between the gene chip, GeneXpert, and Roche proportional methods for the detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis.