1、Med J Chin PLA,Vol.48,No.7,July 28,2023761Xpert MTB/RIF Ultra快速诊断涂阴肺结核的临床价值结核病的预防、诊断与治疗专题研究II基金项目山东省重点研发计划(重大科技创新工程)项目(2021SFGC0504)；山东省医药卫生科技发展计划项目(2019WS523)；山东省中医药科技项目(2020M059)作者简介丁彩红，硕士研究生，主要从事结核病防治方面的研究通信作者熊瑜，E-mail：论著中图分类号R446.5；R521文献标志码ADOI10.11855/j.issn.0577-7402.2257.2023.0427声明本文所有作者声明无
2、利益冲突引用本文丁彩红,王余余,王庆,等.Xpert MTB/RIF Ultra 快速诊断涂阴肺结核的临床价值J.解放军医学杂志,2023,48(7):761-767.收稿日期2022-10-31录用日期2022-12-28上线日期2023-04-27丁彩红，王余余，王庆，高绪胜，解丹，熊瑜*山东大学附属公共卫生临床中心结核内科，山东济南250102摘要目的评估超敏结核分枝杆菌和利福平耐药基因检测(Xpert Ultra)方案检测痰液及支气管肺泡灌洗液(BALF)标本在涂阴肺结核患者中早期、快速诊断的价值。方法选择2020年5月2021年12月在山东省公共卫生临床中心就诊的痰涂片阴性疑似肺结核
3、患者93例，其中临床诊断为涂阴肺结核57例，非肺结核36例。收集所有患者的痰液及BALF标本，分别采用Xpert Ultra、GeneXpert MTB/RIF(Xpert)、BACTEC MGIT 960培养(MGIT 960培养)进行检测。以临床诊断为参考标准，评价3种检测方案及相互联合检测痰液及BALF标本时诊断涂阴肺结核的敏感度、特异度及符合率。结果以临床诊断结果为参考标准，Xpert Ultra检测痰液标本对涂阴肺结核诊断的敏感度明显高于Xpert 56.14%(32/57)vs.36.84%(21/57)，P=0.03和MGIT 960培养56.14%(32/57)vs.33.33
4、%(19/57)，P=0.014；Xpert Ultra检测BALF标本对涂阴肺结核诊断的敏感度明显高于Xpert 75.44%(43/57)vs.56.14%(32/57)，P=0.030和MGIT 960培养75.44%(43/57)vs.38.60%(22/57)，PXpert Ultra+Xpert(0.798)Xpert Ultra+MGIT 960培养(0.789)Xpert Ultra(0.781)Xpert(0.684)MGIT 960培养(0.667)；检测BALF标本，AUC依次为：三者联合(0.895)=Xpert Ultra+Xpert(0.895)Xpert Ultr
5、a+MGIT 960培养(0.877)=Xpert Ultra(0.877)Xpert(0.781)MGIT 960培养(0.693)。3种检测方案均未在入组患者中检测到利福平耐药。结论Xpert Ultra对早期、快速诊断涂阴肺结核具有较高的临床应用价值；其检测BALF的敏感度高于痰液标本，建议优先选择BALF标本。关键词超敏结核分枝杆菌和利福平耐药基因检测；涂阴肺结核；分子诊断技术；耐药；早期诊断Clinical value of Xpert MTB/RIF Ultra in rapid diagnosis of smeared negative pulmonary tuberculosi
6、sDing Cai-Hong,Wang Yu-Yu,Wang Qing,Gao Xu-Sheng,Xie Dan,Xiong Yu*Tuberculosis Medicine,Public Health Clinical Center Affiliated to Shandong University,Jinan,Shandong 250102,China*Corresponding author,E-mail:This work was supported by the Project of Key research and development Program(Major Scienti
7、fic and Technological Innovation Project)of Shandong Province(2021SFGC0504),the Project of Medical and Health Science and Technology Development Plan of Shandong Province(2019WS523),and Traditional Chinese Medicine Science and Technology Project of Shandong Province(2020M059)AbstractObjectiveTo eval
8、uate the value of GeneXpert MTB/RIF Ultra(Xpert Ultra)in the early and rapid diagnosis of sputum and bronchoalveolar lavage fluid(BALF)samples in patients with smeared negative tuberculosis.MethodsA total of 93 patients with sputum smear-negative suspected pulmonary tuberculosis who were admitted to
9、 Shandong Public Health Clinical Center from May 2020 to December 2021 were included in this study.Among them,57 patients were clinically diagnosed as sputum smear-negative pulmonary tuberculosis and 36 patients were non-pulmonary tuberculosis.Sputum and BALF samples were collected from all patients
10、,and Xpert Ultra,GeneXpert MTB/RIF(Xpert),BACTEC MGIT 960 culture(MGIT 960 culture)were performed.解放军医学杂志2023年7月28日第48卷第7期762To evaluate the sensitivity,specificity and coincidence rate of various detection methods and their combined detection of sputum and bronchoalveolar lavage fluid samples in th
11、e diagnosis of smeared negative pulmonary tuberculosis.ResultsTaking clinical diagnosis as the reference standard,the sensitivity of sputum samples detected by Xpert Ultra for the diagnosis of smeared negative pulmonary tuberculosis was significantly higher than that of Xpert 56.14%(32/57)vs.36.84%(
12、21/57),P=0.039 and MGIT 960 culture 56.14%(32/57)vs.33.33%(19/57),P=0.014.The sensitivity of BALF samples detected by Xpert Ultra for the diagnosis of smeared negative pulmonary tuberculosis was significantly higher than that of Xpert 75.44%(43/57)vs.56.14%(32/57),P=0.030 and MGIT 960 culture 75.44%
13、(43/57)vs.38.60%(22/57),PXpert Ultra+Xpert(0.798)Xpert Ultra+MGIT 960 culture(0.789)Xpert Ultra method(0.781)Xpert(0.684)MGIT 960 culture(0.667);Samples of BALF were examined,the AUC was the combination of the three elements(0.895)=Xpert Ultra+Xpert(0.895)Xpert Ultra+MGIT 960 culture(0.877)=Xpert Ul
14、tra method(0.877)Xpert(0.781)culture method(0.693).Rifampicin resistance was not detected in the enrolled samples by the three detection methods.ConclusionsXpert Ultra has high clinical application value in the early and rapid diagnosis of smeared negative pulmonary tuberculosis,and the sensitivity
15、of Xpert Ultra in the detection of BALF is higher than that of sputum sample,so the BALF sample is recommended as prior selection.Key wordsXpert MTB/RIF Ultra;smeared negative pulmonary tuberculosis;molecular diagnostic techniques;drug resistance;early diagnosis结核病(tuberculosis，TB)是严重危及公共卫生的重大传染性疾病之
16、一。2021年全球新发结核病1060万例，死亡约160万例，是仅次于新型冠状病毒感染的全球第二大单一传染源致死原因1。在2021年全球新诊断的640万例结核病中，仅38%是采用快速分子诊断技术诊断的，其中检出耐药结核病166 991例，较2020年增多6.4%。我国2021年估算的新发结核病78万例，为全球第三大结核病高负担国家1，结核病的诊断和治疗仍存在较大缺口。抗酸杆菌涂片染色镜检法和结核分枝杆菌培养法是诊断结核病的传统实验室检查方法。萋尼抗酸染色涂片镜检方法敏感度(20%30%)较低，诊断涂阴肺结核时存在一定局限性2。结核分枝杆菌培养及药物敏感性试验是结核病和耐药结核病诊断的“金标准”，但因培养等待时间较长，不利于结核病和耐药结核病的早期快速诊断3-4。研究发现，有30%60%的肺结核患者往往因痰涂片阴性无细菌学依据、痰结核分枝杆菌培养周期长等原因，导致涂阴肺结核患者延误诊治4-5，其病死率近20%；10%20%的肺结核传播可归因于涂阴肺结核患者6。因此，快速、准确诊断涂阴肺结核是加强结核病控制的重要措施。结核分枝杆菌和利福平耐药基因检测(GeneXpert MTB/RIF，Xp