某三甲医院肺外非结核分枝杆菌感染的微生物学特征分析

Microbiological Characteristics of Extrapulmonary Nontuberculous Mycobacterial Infections in a Tertiary Hospital

摘要

目的 本研究旨在分析某三甲医院肺外非结核分枝杆菌（extrapulmonary nontuberculous mycobacterial, ENTM）感染的微生物学特征，为ENTM感染的临床诊疗提供数据支撑。方法 回顾性分析四川大学华西医院2020–2023年分枝杆菌培养结果，共纳入ENTM感染确诊病例68例，所有纳入病例均符合《非结核分枝杆菌病诊断与治疗指南（2020年版）》中肺外感染的诊断标准。分析纳入病例的人口学特征、菌种分布特征及药敏试验结果。采用质谱技术进行微生物菌种鉴定，采用微量肉汤稀释法进行药敏试验。结果 68例ENTM感染病例中，男女比例为1∶1.2，40～59岁为主要感染人群，感染部位以皮肤软组织最常见。标本主要来源为脓液（33.8%，23例），其次为病理组织（26.5%，18例）；确诊患者主要来源于感染科（29.4%，20例）。68例ENTM中，快速生长型分枝杆菌（rapid-growing mycobacterial, RGM）占32.4%（22例），最常见菌种为脓肿分枝杆菌；缓慢生长型分枝杆菌（slowly-growing mycobacterial, SGM）占比67.6%（46例），最常见菌种为胞内分枝杆菌和海分枝杆菌。RGM对利福平、利福布汀等抗生素具有较高的最低抑菌浓度（minimal inhibitory concentration, MIC），对克拉霉素、阿米卡星具有较低MIC值；SGM对大多数抗生素均具有较低的MIC值。结论 本研究中ENTM感染最常累及皮肤软组织，病原菌以SGM为主，其中胞内分枝杆菌占据主导地位。RGM对克拉霉素和阿米卡星敏感，可为经验性抗感染治疗提供参考依据；SGM虽对多数受试药物表现出较低的MIC，但临床治疗时仍需采用联合用药方案，并充分评估治疗失败的风险。

Abstract

Objective To analyze the microbiological characteristics of extrapulmonary nontuberculous mycobacterial (ENTM) infections in a tertiary hospital and to provide data to support clinical diagnosis and treatment of ENTM infections. Methods A retrospective analysis was conducted on mycobacterial culture results from West China Hospital, Sichuan University from 2020 to 2023. A total of 68 confirmed cases of ENTM infection were enrolled, with all of which meeting the diagnostic criteria for extrapulmonary infection outlined in the Guidelines for the Diagnosis and Treatment of Nontuberculous Mycobacterial Disease (2020). Demographic data, strain distribution, and drug susceptibility test results were analyzed. Microbial species identification was performed using mass spectrometry, and drug susceptibility was assessed using the microbroth microdilution method. Results Among the 68 ENTM cases, the male-to-female ratio was 1 to 1.2, with individuals aged 40-59 years being the main affected group population. The most common sites of infection were the skin and soft tissues. The primary specimen source was pus (33.8%, 23 cases), followed by pathological tissues (26.5%, 18 cases). The Department of Infectious Diseases was the main source of confirmed cases (29.4%, 20 cases). Among the 68 EMTM cases, rapid-growing mycobacteria (RGM) accounted for 32.4% (22 cases), withMycobacterium abscessus being the predominant species, while slowly-growing mycobacteria (SGM) accounted for 67.6% (46 cases), with Mycobacterium intracellulare and Mycobacterium marinum being the predominant species. RGM exhibited higher minimum inhibitory concentration (MICs) for rifampicin and rifabutin but lower MICs for clarithromycin and amikacin. In contrast, SGM demonstrated low MICs for most antibiotics tested. Conclusion In this study, ENTM infections most commonly involve the skin and soft tissues, with SGM being the predominant pathogens and Mycobacterium intracellulare being the dominant species. RGM shows susceptibility to clarithromycin and amikacin, which provides a basis for empirical anti-infective therapy. Although SGM exhibits low MICs to most tested antimicrobial agents, combination regimens remain necessary in clinical practice, and the risk of treatment failure should be thoroughly evaluated.

关键词

非结核分枝杆菌感染 / 微生物敏感性试验 / 抗菌药

Key words

Mycobacterial infections, nontuberculous / Microbial sensitivity tests / Anti-bacterial agents

参考文献

[1] LIANG Q, JIANG X, JIA J, et al. An early and trustable indicator suggestive of non-tuberculosis mycobacteria isolation in a high tuberculosis burden setting. J Infect, 2024, 88(5): 106149. doi: 10.1016/j.jinf.2024.106149.

[2] METERSKY M L, FRAULINO D, MONDAY L, et al. Current challenges in pulmonary nontuberculous mycobacterial infection: a case series with literature review. Postgrad Med, 2024, 136(7): 770-781. doi: 10.1080/00325481.2024.2401766.

[3] JARCHOW-MACDONALD A, SMITH M, SEAGAR A L, et al. Changing incidence and characteristics of nontuberculous mycobacterial infections in scotland and comparison with Mycobacterium tuberculosis complex incidence (2011 to 2019). Open Forum Infect Dis, 2023, 10(1): ofac665. doi: 10.1093/ofid/ofac665.

[4] WANG D M, LIU H, ZHENG Y L, et al. Epidemiology of nontuberculous mycobacteria in tuberculosis suspects, Southwest of China, 2017-2022. Front Cell Infect Microbiol, 2023, 13: 1282902. doi: 10.3389/fcimb.2023.1282902.

[5] OMORI K, KITAGAWA H, YAMAGUCHI K, et al. Clinical characteristics of extrapulmonary nontuberculous mycobacteria infections in comparison with pulmonary infections: a single-center, retrospective study in Japan. J Infect Chemother, 2023, 29(9): 875-881. doi: 10.1016/j.jiac.2023.05.013.

[6] KIM S, KIM A R, BAE M, et al. Clinical characteristics and outcomes of extrapulmonary nontuberculous mycobacterial infections in a tertiary-care hospital: a retrospective study. J Clin Med, 2024, 13(15): 4373. doi: 10.3390/jcm13154373.

[7] FUJISHIMA C, TAHARA J, MUNEMOTO S, et al. Cutaneous nontuberculous mycobacterial infections in Japan: review of the Japanese literature. J Dermatol, 2022, 49(11): 1075-1084. doi: 10.1111/1346-8138.16531.

[8] TANG M, ZENG W, QIU Y, et al. Clinical features of rare disseminated Mycobacterium colombiense infection in nine patients who are HIV-negative in Guangxi, China. Int J Infect Dis, 2023, 128: 321-324. doi: 10.1016/j.ijid.2023.01.002.

[9] Clinical and Laboratory Standards Institute. Performance standards for susceptibility testing of Mycobacteria, Nocardia spp., and other Aerobic actinomycetes (CLSI document M62). Wayne, PA: Clinical and Laboratory Standards Institute, 2018.

[10] SI Z, SUN Y, TAN C, et al. A cationic main-chain poly(carbonate-imidazolium) potent against Mycobacterium abscessus and other resistant bacteria in mice. Biomaterials, 2025, 316: 123003. doi: 10.1016/j.biomaterials.2024.123003.

[11] LEESTEMAKER-PALMER A, BERMUDEZ L E. Mycobacteroides abscessus ability to interact with the host mucosal cells plays an important role in pathogenesis of the infection. Crit Rev Microbiol, 2025, 51(5): 792-804. doi: 10.1080/1040841X.2024.2418130.

[12] Chinese Society for Tuberculosis, Chinese Medical Association. The Guidelines for diagnosis and treatment of non-tuberculous mycobacteria disease (2020 edition). Chin J Tuberc Respir Dis, 2020, 43(11): 918-946. doi: 10.12025/j.issn.1008-6358.2023.20230998.

[13] HELLE O M B, KANTHALI M, ISHTIAQ S, et al. Diagnosing adult and pediatric extrapulmonary tuberculosis by MPT64 antigen detection with immunohistochemistry and immunocytochemistry using reproduced polyclonal antibodies. J Pathol Clin Res, 2024, 10(3): e12373. doi: 10.1002/2056-4538.12373.

[14] RINDI L, PUGLISI V, FRANCONI I, et al. Rapid and accurate identification of Nontuberculous Mycobacteria directly from positive primary MGIT cultures by MALDI-TOF MS. Microorganisms, 2022, 10(7): 1447. doi: 10.3390/microorganisms10071447.

[15] BAGNARINO J, BARBARINI D, RUSSELLO G, et al. Mycobacterium chimaera identification using MALDI-TOF MS technology: a practical approach for the clinical microbiology laboratories. Microorganisms, 2022, 10(6): 1184. doi: 10.3390/microorganisms10061184.

[16] 秦雪娅, 林勇, 周聪, 等. 基于MALDI-TOF MS对脓肿分枝杆菌脓肿亚种和马赛亚种的鉴别及特征分析. 临床检验杂志, 2025, 43(2): 81-87. doi: 10.13602/j.cnki.jcls.2025.02.01.

[17] QIN X Y, LIN Y, ZHOU C, et al. Identification of Mycobacterium abscessus subsp. abscessus and subsp. massiliense based on MALDI-TOF MS and analysis for their characteristics. Chin J Clin Lab Sci, 2025, 43(2): 81-87. doi: 10.13602/j.cnki.jcls.2025.02.01.

[18] BROWN-ELLIOTT B A, FRITSCHE T R, OLSON B J, et al. Comparison of two commercial matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) systems for identification of Nontuberculous Mycobacteria. Am J Clin Pathol, 2019, 152(4): 527-536. doi: 10.1093/ajcp/aqz073.

[19] 宋启飞, 戴仲秋, 杜宝中, 等. 结核分枝杆菌复合体VNTR位点多态性与菌株MALDI-TOF MS蛋白谱差异的关系. 四川大学学报(医学版), 2019, 50(6): 872-877.

[20] SONG Q F, DAI Z Q, DU B Z, et al. Relationship between the VNTR loci polymorphism and MALDI-TOF MS protein profile diversity in Mycobacterium tuberculosis complex. J Sichuan Univ (Med Sci Edi), 2019, 50(6): 872-877.

[21] 罗佳, 喻秋菊, 林钰灵, 等. 2016-2021年四川地区非结核分枝杆菌感染临床特点分析. 四川大学学报(医学版), 2022, 53(5): 890-895. doi: 10.12182/20220960503.

[22] LUO J, YU Q J, LIN Y L, et al. Clinical characteristics of Nontuberculous Mycobacterium infection cases in Sichuan, China in 2016-2021: a retrospective study. J Sichuan Univ (Med Sci Edi), 2022, 53(5): 890-895. doi: 10.12182/20220960503.

[23] LIN W H, YAO C, MEI L, et al. Screening, epidemic trends and drug sensitivity analysis of nontuberculous mycobacteria in a local area of China. Am J Transl Res, 2024, 16(7): 3298-3305. doi: 10.62347/MAJY5046.

[24] LIU X, LIN Z, LI Y, et al. Analysis of Clinical Isolation Characteristics of Nontuberculous Mycobacteria and drug sensitivity of rapidly growing Mycobacteria in the General Hospital of Guangzhou, China. Infect Drug Resist, 2024, 17: 4079-4088. doi: 10.2147/IDR.S465468.

[25] CHEN P, MENG Y, LIU T, et al. Sensitive urine immunoassay for visualization of Lipoarabinomannan for noninvasive tuberculosis diagnosis. ACS Nano, 2023, 17(7): 6998-7006. doi: 10.1021/acsnano.3c01374.

[26] LI L, HENKLE E, YOUNGQUIST B M, et al. Serum cell-free DNA-based detection of Mycobacterium avium complex infection. Am J Respir Crit Care Med, 2024, 209(10): 1246-1254. doi: 10.1164/rccm.202303-0401OC.