2026 年第 7 期 第 21 卷

多色探针熔解曲线分析法对6种抗结核药物的耐药性诊断价值

Diagnostic value of multicolor probe melting curve analysis for drug resistance to six antituberculosis drugs

作者：张云婷郝跃鹏冯建纯贾涤静马伟立

英文作者：Zhang Yunting Hao Yuepeng Feng Jianchun Jia Dijing Ma Weili

单位：河北省胸科医院感染性疾病实验诊断中心河北省肺病重点实验室，石家庄050000

英文单位：Experimental Diagnostic Center for Infectious Diseases Hebei Chest Hospital Hebei Key Laboratory of Pulmonary Diseases Shijiazhuang 050000 China

关键词：结核病；多色探针熔解曲线分析法；结核分枝杆菌；耐药性；耐多药肺结核

英文关键词：Tuberculosis;Multicolorprobemeltingcurveanalysis;Mycobacteriumtuberculosis;Drugresistance;Multidrug-resistantpulmonarytuberculosis

• 摘要：

• 目的 探讨多色探针熔解曲线分析法（MMCA）对6种抗结核药物的耐药性诊断效果并探讨耐多药肺结核（MDR-TB）的影响因素及预测价值。方法 选取2024年1月至2025年3月河北省胸科医院住院诊治的1 724例疑似结核病患者为研究对象，收集患者清晨痰液标本进行结核分枝杆菌（MTB）培养，经分枝杆菌生长指示管960系统（MGIT960）液体快速MTB培养法鉴定有574例样本为MTB阳性。分别采用MMCA和MGIT960液体快速MTB培养法检测利福平、异烟肼、乙胺丁醇、链霉素、左氧氟沙星和莫西沙星等6种抗结核药物的耐药性，分析MMCA对6种抗结核药物的诊断效能。根据诊断结果将患者分成MDR-TB组和非MDR-TB组，比较2组的临床资料，使用多因素Logistic回归模型分析MDR-TB的影响因素，并采用受试者工作特征（ROC）曲线评估模型的预测效能。结果 以MGIT960液体快速MTB培养法为耐药诊断的金标准，MMCA检测利福平、异烟肼、乙胺丁醇、链霉素、左氧氟沙星、莫西沙星的敏感度分别为95.24%、94.87%、92.75%、96.97%、92.42%、89.47%，特异度分别为98.52%、97.37%、98.02%、98.74%、97.64%、95.74%，一致性分析Kappa分别为0.941、0.917、0.880、0.946、0.861、0.758。经MGIT960液体快速MTB培养法诊断有136例患者为MDR-TB，438例为非MDR-TB。多因素Logistic回归分析显示，居住地、治疗史、结核病接触史、结核空洞均为MDR-TB的独立危险因素，基于此建立回归方程，模型预测MDR-TB的曲线下面积为0.843（95%置信区间：0.805～0.882），敏感度为66.20%，特异度为87.00%。结论 MMCA对利福平、异烟肼、乙胺丁醇、链霉素、左氧氟沙星、莫西沙星耐药性的检测具有较好的诊断效能，且便于检测，有助于MDR-TB的快速筛查。当患者居住地为农村、复治、有结核病接触史、存在结核空洞等多种表现共存时，高度提示为MDR-TB。

• Objective To investigate the diagnostic efficacy of multicolor probe melting curve analysis (MMCA) for drug resistance to six antituberculosis drugs, and to explore the influencing factors and predictive value of multidrug-resistant pulmonary tuberculosis (MDR-TB). Methods A total of 1 724 patients suspected to be tuberculosis who were hospitalized and treated in Hebei Chest Hospital from January 2024 to March 2025 were enrolled as study subjects. Early morning sputum samples were collected for Mycobacterium tuberculosis (MTB) culture, and 574 samples were identified as MTB-positive by mycobacteria growth indicator tube 960 system (MGIT960) rapid liquid MTB culture system. MMCA and MGIT960 rapid liquid MTB culture were used to detect drug resistance to six antituberculosis drugs including rifampicin, isoniazid, ethambutol, streptomycin, levofloxacin and moxifloxacin, respectively, and the diagnostic efficacy of MMCA for the six drugs was analyzed. Patients were divided into MDR-TB group and non-MDR-TB group according to the diagnostic results. Clinical data were compared between the two groups. Multivariate Logistic regression model was used to analyze the influencing factors of MDR-TB, and receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of the model. Results Taking MGIT960 rapid liquid MTB culture as the gold standard for drug resistance diagnosis, the sensitivities of MMCA for detecting rifampicin, isoniazid, ethambutol, streptomycin, levofloxacin and moxifloxacin were 95.24%, 94.87%, 92.75%, 96.97%, 92.42% and 89.47%, respectively; the specificities were 98.52%, 97.37%, 98.02%, 98.74%, 97.64% and 95.74%, respectively; and the Kappa values of consistency analysis were 0.941, 0.917, 0.880, 0.946, 0.861 and 0.758, respectively. A total of 136 patients were diagnosed with MDR-TB and 438 with non-MDR-TB by MGIT960 rapid liquid MTB culture. Multivariate Logistic regression analysis showed that residence, treatment history, tuberculosis contact history and tuberculous cavity were independent risk factors for MDR-TB. A regression equation was established based on these factors, and the area under the curve of the model for predicting MDR-TB was 0.843(95% confidence interval: 0.805-0.882), with a sensitivity of 66.20% and a specificity of 87.00%. Conclusion MMCA shows favorable diagnostic efficacy in detecting drug resistance to rifampicin, isoniazid, ethambutol, streptomycin, levofloxacin and moxifloxacin, and is easy to operate, facilitating rapid screening of MDR-TB. The coexistence of rural residence, retreatment, tuberculosis contact history and tuberculous cavity strongly suggests MDR-TB.