非结核分枝杆菌病分子生物学诊断专家共识

doi:10.19982/j.issn.1000-6621.20250225

摘要/Abstract

摘要：

非结核分枝杆菌(nontuberculous mycobacteria,NTM)病呈现上升趋势。传统的抗酸染色涂片和分枝杆菌培养等方法存在敏感度低、耗时长、无法鉴定至具体菌种等问题,而分子生物学检测技术在NTM病的诊断和菌种鉴定方面展现了独特的优势和巨大的应用前景。目前,我国在NTM病分子诊断方面缺乏系统全面的指导性共识。为规范NTM病分子诊断技术的临床应用,提升广大医务工作者NTM病的诊治能力,中国防痨协会非结核分枝杆菌病专业分会组织我国NTM病专家、感染病学专家、微生物学专家和方法学专家组成编写组,经过系统的文献复习、多轮线上线下讨论和问卷调查,评估分子生物学检测技术的优缺点及应用现状,就NTM病分子生物学诊断的重要问题进行讨论,经过多次会议讨论和修订,最终形成本共识。本共识针对NTM病诊断的分子靶标、分子生物学诊断技术、检测结果解读等核心问题,最终形成11条推荐意见。本共识系统构建了NTM病分子生物学诊断的技术框架和临床应用路径,解决了技术碎片化、解读标准化不足等核心问题,为临床医生、检验科室及公共卫生部门提供了指导。

关键词: 分枝杆菌感染, 分子生物学, 诊断,鉴别, 总结性报告

Abstract:

The incidence of nontuberculous mycobacteria (NTM) disease has been on the rise. Traditional methods such as acid-fast bacilli staining and mycobacterial culture suffer from limitations including low sensitivity, being time-consuming, and inability to identify specific species. In contrast, molecular biology detection technologies have demonstrated unique advantages and great application prospects in the diagnosis of NTM diseases and precise species identification. However, there is lack of systematic and comprehensive guideline for the molecular diagnosis of NTM disease in China. In order to standardize the clinical application of molecular diagnostic techniques for NTM diseases and enhance the diagnosis and treatment capabilities of medical professionals, the Nontuberculous Mycobacterial Diseases Branch of Chinese Antituberculosis Association organized a writing group composed of domestic experts in the fields of NTM diseases, infectious diseases, microbiology, and methodology. Through systematic literature reviews, multiple rounds of online and offline discussions, and questionnaire surveys, the group evaluated the respective merits, limitations, and implementation status of current molecular detection technologies, discussed key issues in molecular diagnosis of NTM diseases, and ultimately formulated this consensus after iterative revisions through multiple consensus conferences. Focusing on core issues such as molecular targets for NTM disease diagnosis, molecular biological diagnostic techniques, and standardized interpretation protocols, the consensus formulated 11 evidence-based recommendations. It systematically establishes a technical framework and clinical application pathway for molecular biological diagnosis of NTM diseases, addressing core challenges like technical fragmentation and inconsistent interpretation standards. It provides actionable guidance for clinicians, clinical laboratories, and public health departments.

Key words: Mycobacterium infections, Molecular biology, Diagnosis, differential, Consensus development conference

中图分类号:

R378.91
R516

中国防痨协会非结核分枝杆菌病分会. 非结核分枝杆菌病分子生物学诊断专家共识[J]. 中国防痨杂志, 2025, 47(8): 961-975. doi: 10.19982/j.issn.1000-6621.20250225

Nontuberculous Mycobacterial Diseases Branch of Chinese Antituberculosis Association. Expert consensus on molecular biology diagnosis of nontuberculous mycobacteria diseases[J]. Chinese Journal of Antituberculosis, 2025, 47(8): 961-975. doi: 10.19982/j.issn.1000-6621.20250225

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靶标	推荐鉴定菌种	缺陷	备注
16S rRNA	鉴定临床常见非结核分枝杆菌,如鸟分枝杆菌复合群、脓肿分枝杆菌复合群、偶发分枝杆菌复合群等,以及戈登分枝杆菌、蟾蜍分枝杆菌、玛尔摩分枝杆菌、瘰疬分枝杆菌、草分枝杆菌、耻垢分枝杆菌	不能区分堪萨斯和胃分枝杆菌、海分枝杆菌和溃疡分枝杆菌、龟分枝杆菌和脓肿分枝杆菌,对鸟分枝杆菌复合群、脓肿分枝杆菌复合群、偶发分枝杆菌复合群亚种的鉴定能力弱	现有数据库最完整
hsp65	常见非结核分枝杆菌的鉴定,如鸟分枝杆菌复合群和脓肿分枝杆菌复合群及亚种,堪萨斯分枝杆菌、胃分枝杆菌、海分枝杆菌、溃疡分枝杆菌、龟分枝杆菌、瘰疬分枝杆菌、耻垢分枝杆菌、草分枝杆菌等	对偶发分枝杆菌复合群亚种和猿分枝杆菌的鉴定能力弱	鉴别能力优于其他靶标
rpoB	常见非结核分枝杆菌的鉴定,如脓肿分枝杆菌复合群及亚种,鸟分枝杆菌、胞内分枝杆菌、龟分枝杆菌、堪萨斯分枝杆菌、胃分枝杆菌、海分枝杆菌、溃疡分枝杆菌等	对土分枝杆菌的鉴定能力弱	同时检测利福平耐药性
ITS	常见缓慢生长型分枝杆菌的鉴定,如鸟分枝杆菌复合群及亚种,胃分枝杆菌、堪萨斯分枝杆菌、瘰疬分枝杆菌、戈登分枝杆菌、玛尔摩分枝杆菌和苏尔佳分枝杆菌	对快速生长型分枝杆菌鉴定能力弱	通常作为16S rRNA的补充

技术名称	优势	缺陷
实时荧光PCR	可直接检测临床样本,应用广泛,敏感度和特异度较高	适用于初筛,部分技术不能进行非结核分枝杆菌的种属鉴定
荧光PCR熔解曲线	可直接检测临床样本,方便快捷,准确率高,经济成本低	仅能鉴定试剂盒内特定的临床常见菌种
一代测序	敏感度和特异度高,是目前非结核分枝杆菌菌种鉴定的“金标准”	耗时,操作复杂伴一定的检测污染风险
高通量测序	高通量,靶向测序可检测到预设的耐药相关基因的突变类型;宏基因组测序可同时检测包括非结核分枝杆菌在内的多种病原微生物,对混合感染有优势;全基因组测序可获得全部基因信息,有助于发现新的非结核分枝杆菌菌种	经济成本高,对样本、设备和结果解读的要求高;全基因组测序不能直接检测临床样本,耗时长,不适合大规模应用
核酸飞行时间质谱	高通量,敏感度和特异度高,可以检测分枝杆菌的混合感染和耐药相关基因的突变类型	经济成本较高,操作较为复杂
线性探针	价格低廉,敏感度和特异度较高	需要专门仪器,操作繁琐
PCR反向斑点杂交	可直接检测临床样本,敏感度和特异度较高	自动化程度偏低
基因芯片	通量较高,简单快速,敏感度和特异度较高	需PCR后处理,容易造成污染

器官与部位	常见感染菌种
肺	鸟分枝杆菌复合群、脓肿分枝杆菌复合群、堪萨斯分枝杆菌、蟾蜍分枝杆菌等
皮肤/软组织	海分枝杆菌、脓肿分枝杆菌复合群、龟分枝杆菌、偶发分枝杆菌复合群和溃疡分枝杆菌等
淋巴结	鸟分枝杆菌复合群、嗜血分枝杆菌、瘰疬分枝杆菌、玛尔摩分枝杆菌等
播散性非结核分枝杆菌病	鸟分枝杆菌复合群、龟分枝杆菌、嗜血分枝杆菌和堪萨斯分枝杆菌等
角膜/脉络膜	偶发分枝杆菌复合群、龟分枝杆菌和脓肿分枝杆菌复合群等
骨关节	海分枝杆菌、鸟分枝杆菌复合群、脓肿分枝杆菌复合群、偶发分枝杆菌复合群和龟分枝杆菌等
骨髓	脓肿分枝杆菌复合群、偶发分枝杆菌复合群和龟分枝杆菌等
牙龈	偶发分枝杆菌复合群和龟分枝杆菌
人工心脏/瓣膜置换术后	奇美拉分枝杆菌、偶发分枝杆菌复合群、龟分枝杆菌和脓肿分枝杆菌复合群等
实体器官移植术后	鸟分枝杆菌复合群