初治肺结核患者耐药情况、耐药危险因素、耐药基因及其辅助诊断技术研究

Drug Resistance Situation,Risk Factors for Drug Resistance,Drug Resistance Related Genes and Aided Diagnostic Techniques in Untreated Patients with Pulmonary Tuberculosis

目的探讨初治肺结核患者耐药情况、耐药危险因素、耐药基因及其辅助诊断技术。方法选取2015年7—12月西安市胸科医院收治的初治肺结核患者478例,均进行痰培养及药敏试验,回顾性分析其耐药情况、耐药危险因素、耐药基因检测结果、辅助诊断技术检测结果。结果 (1)478例患者中126例耐药,耐药率为26.4%。478例患者中对一线抗结核药物异烟肼耐药64例(13.4%),利福平耐药33例(6.9%),乙胺丁醇耐药20例(4.2%),链霉素耐药75例(15.7%);对二线抗结核药物左氧氟沙星耐药28例(5.9%),利福喷丁耐药28例(5.9%),莫西沙星耐药23例(4.8%),对氨基水杨酸钠耐药21例(4.4%),卷曲霉素耐药7例(1.5%),丙硫异烟胺耐药2例(0.4%),阿米卡星耐药2例(0.4%);单耐药结核病(MR-TB)50例(10.5%),耐多药结核病(MDR-TB)30例(6.3%),广泛耐药结核病(XDR-TB)21例(4.4%),其他25例(5.2%)。(2)多因素Logistic回归分析结果显示,年龄、双肺受累肺野数是初治肺结核患者耐药的危险因素(P<0.05)。(3)利福平耐药相关rpoB基因突变诊断初治肺结核患者耐药的灵敏度为83.3%,特异度为99.0%,阳性预测值为83.3%,阴性预测值为99.0%,Kappa值为0.823;异烟肼耐药相关katG/inhA基因突变诊断初治肺结核患者耐药的灵敏度为58.6%,特异度为100.0%,阳性预测值为100.0%,阴性预测值为93.8%,Kappa值为0.709。(4)双通道聚合酶链反应(PCR)结核分枝杆菌RNA扩增诊断初治肺结核患者耐药的灵敏度为75.2%,特异度为34.9%,阳性预测值为27.5%,阴性预测值为81.1%,Kappa值为0.449;双通道PCR结核分歧杆菌DNA扩增诊断初治肺结核患者耐药的灵敏度为82.4%,特异度为29.4%,阳性预测值为29.9%,阴性预测值为82.1%,Kappa值为0.436;结核感染T细胞检测诊断初治肺结核患者耐药的灵敏度为71.4%,特异度为22.7%,阳性预测值为26.0%,阴性预测值为67.7%,Kappa值为0.361;LAM抗体诊断初治肺结核患者耐药的灵敏度为65.3%,特异度为39.7%,阳性预测值为28.2%,阴性预测值为75.9%,Kappa值为0.465;38DKa抗体诊断初治肺结核患者耐药的灵敏度为69.5%,特异度为43.7%,阳性预测值为30.9%,阴性预测值为79.8%,Kappa值为0.506;16DKa抗体诊断初治肺结核患者耐药的灵敏度为2.5%,特异度为92.2%,阳性预测值为12.0%,阴性预测值为72.5%,Kappa值为0.691。结论初治肺结核患者耐药率为26.4%,MDR-TB检出率为6.3%,应注意MDR-TB的流行;年龄、双肺受累肺野数是初治肺结核患者耐药的危险因素,应加以重视并注意耐药筛查;rpoB基因突变对利福平耐药的诊断价值较高,但katG/inhA基因突变对异烟肼耐药的诊断价值一般,双通道PCR、结核感染T细胞检测、结核抗体三项对初治肺结核患者耐药的诊断价值亦一般,需结合地区耐药结核病流行规律选择应用。

Objective To investigate the drug resistance situation,risk factors for drug resistance,drug resistance related gene and aided diagnostic techniques in untreated patients with pulmonary tuberculosis. Methods A total of 478 untreated patients with pulmonary tuberculosis were selected in Xi’an Chest Hospital from July to December 2015,all of them received sputum culture and drug sensitivity test,the drug resistance situation,risk factors for drug resistance,testing results of drug resistance related gene and aided diagnostic techniques were retrospectively analyzed. Results(1)The drug resistance rate was 26.4%(126/478). Of the 478 patients,64 cases(13.4%)found drug resistance to isoniazide,33 cases(6.9%)to rifampicin,20 cases(4.2%)to ethambutol,75 cases(15.7%)to streptomycin,which belongs to first-line anti-tuberculosis drugs;28 cases(5.9%)found to rug resistance to levofloxacin,28 cases(5.9%)to rifapentine,23 cases(4.8%)to moxifloxacin,21 cases(4.4%)to sodium para-aminosalicylate,7 cases(1.5%)to capreomycin,2 case(0.4%)to protionamide,2 cases(0.4%)to amikacin,which belongs to second-line anti-tuberculosis drugs;50 cases(10.5%)were MR-TB,30 cases(6.3%)were MDR-TB,21 cases(4.4%)were XDR-TB,25 case(5.2%)were other types.(2)Multivariate Logistic regression analysis results showed that,age and affected pulmonary fields in bilateral lungs were risk factors for drug resistance in untreated patients with pulmonary tuberculosis(P<0.05).(3)Sensitivity of rifampin-resistant related rpoB gene mutation on drug resistance was 83.3% in untreated patients with pulmonary tuberculosis,specificity was 99.0%,positive predictive value was 83.3%,negative predictive value was 99.0%,Kappa value was 0.823;that of isoniazid-resistant related katG/inhA gene mutation was 58.6%,100.0%,100.0%,93.8%,0.709,respectively.(4)Sensitivity of Mycobacterium tuberculosis RNA amplification in dual-channel PCR on drug resistance was 75.2% in untreated patients with pulmonary tuberculosis,specificity was 34.9%,positive predictive value was 27.5%,negative predictive value was 81.1%,Kappa value was 0.449;that of Mycobacterium tuberculosis DNA amplification in dual-channel PCR was 82.4%,29.4%,29.9%,82.1%,0.436,respectively;that of T cell test for tuberculosis infection was 71.4%,22.7%,26.0%,67.7%,0.361,respectively;that of LAM antibody was 65.3%,39.7%,28.2%,75.9%,0.465,respectively;that of 38 DKa antibody was 69.5%,43.7%,30.9%,79.8%,0.506,respectively;that of 16 DKa antibody was 2.5%,92.2%,12.0%,72.5%,0.691,respectively. Conclusion The drug resistance rate is 26.4% in untreated patients with pulmonary tuberculosis,and detection rate of MDR-TB is 6.3%,that we should pay attention to the prevalence of MDR-TB;age and affected pulmonary fields in bilateral lungs are risk factors for drug resistance in untreated patients with pulmonary tuberculosis,that we should pay more attention to and strengthen the screening of drug resistance;rpoB gene mutation has relatively high diagnostic value on rifampin resistance,but diagnostic value of katG/inhA gene mutation,dual-channel PCR,T cell test for tuberculosis infection,triune tuberculosis antibodies is not desired,that we should make a choice according to the regional epidemic features of drug-resistant tuberculosis.