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中国防痨杂志 ›› 2026, Vol. 48 ›› Issue (10): 1523-1530.doi: 10.19982/j.issn.1000-6621.20260349

• 论著 • 上一篇    下一篇

肺结核患者对贝达喹啉、德拉马尼和利奈唑胺的耐药情况分析

苏达宏1, 李晓丽2, 杨斌1, 施亦衡1, 林威兵1, 苗甜甜1, 赵金凤1, 马尚1, 霍凤敏1, 王桂荣1()   

  1. 1 首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所检验科, 北京 101149
    2 北京百普赛斯生物科技股份有限公司, 北京 100176
  • 收稿日期:2026-06-12 出版日期:2026-10-10 发布日期:2026-09-30
  • 通信作者: 王桂荣,Email:wangguirong1230@ccmu.edu.cn
  • 基金资助:
    新发突发与重大传染病防控国家科技重大专项(2025ZD01907903);北京市医疗卫生领域高层次创新创业人才“青苗计划”(G202522153);细胞与基因治疗精准检测与质量评价北京市重点实验室

Analysis of drug resistance to bedaquiline, delamanid and linezolid in patients with pulmonary tuberculosis

Su Dahong1, Li Xiaoli2, Yang Bin1, Shi Yiheng1, Lin Weibing1, Miao Tiantian1, Zhao Jinfeng1, Ma Shang1, Huo Fengmin1, Wang Guirong1()   

  1. 1 Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing 101149, China
    2 ACROBiosystems, Beijing 100176, China
  • Received:2026-06-12 Online:2026-10-10 Published:2026-09-30
  • Contact: Wang Guirong, Email: wangguirong1230@ccmu.edu.cn
  • Supported by:
    National Science and Technology Major Project for the Prevention and Control of Emerging, Sudden-Onset and Major Infectious Diseases(2025ZD01907903);“Qingmiao” Program for High-level Innovative and Entrepreneurial Talents in the Medical and Health Sector of Beijing(G202522153);Beijing Key Laboratory of Precision Detection and Quality Evaluation for Cell and Gene Therapy

摘要:

目的: 了解肺结核患者对贝达喹啉(bedaquiline,Bdq)、德拉马尼(delamanid,Dlm)、利奈唑胺(linezolid,Lzd)的耐药特点,为临床医生制定耐药肺结核患者个体化治疗方案提供参考。方法: 采用回顾性研究方法,收集2025年3—12月首都医科大学附属北京胸科医院收治的445例门诊及住院肺结核患者的临床资料,包括性别、年龄、职业、居住地、病史、用药方案、药物敏感试验结果等。药物敏感试验采用分枝杆菌微孔板药敏检测技术,检测研究对象临床分离菌株对异烟肼、利福平、乙胺丁醇、Dlm、Bdq、利福布汀、左氧氟沙星、莫西沙星、卡那霉素、阿米卡星、环丝氨酸、丙硫异烟胺、对氨基水杨酸、Lzd、吡嗪酰胺和氯法齐明16种药物的敏感性。分析肺结核患者的基本信息、初治或复治情况、耐药情况,以及使用过Bdq、Dlm、Lzd的患者中相应药物的耐药情况。结果: 445例肺结核患者对16种抗结核药的总耐药率为47.9%(213/445),利福平耐药率、耐多药率、广泛耐药率分别为30.1%(134/445)、23.4%(104/445)和3.8%(17/445)。Bdq、Dlm、Lzd的耐药率分别为2.7%(12/445)、4.0%(18/445)、3.8%(17/445),且复治患者的耐药率均明显高于初治患者[Bdq:6.4%(11/171)对比 0.4%(1/274);Dlm:7.0%(12/171)对比2.2%(6/274);Lzd:8.8%(15/171)对比0.7%(2/274)],差异均有统计学意义(χ2值分别为12.552、6.323、16.409,P值均<0.05)。耐多药/利福平耐药肺结核患者对Bdq、Dlm、Lzd的耐药率均明显高于非利福平耐药肺结核患者[Bdq:6.7%(9/134)对比1.0%(3/311);Dlm:7.5%(10/134)对比2.6%(8/311);Lzd:11.9%(16/134)对比0.3%(1/311)],差异均有统计学意义(χ2值分别为9.717、5.770、31.318,P值均<0.05)。耐多药/利福平耐药肺结核患者中Bdq+Dlm、Bdq+Lzd、Dlm+Lzd、Bdq+Dlm+Lzd 的耐药率分别为4.5%(6/134)、3.7%(5/134)、5.2%(7/134)、3.0%(4/134)。使用Bdq的患者对Bdq的耐药率为8.4%(8/95),明显高于未使用者[1.1%(4/350)];使用Dlm的患者对Dlm的耐药率为9.1%(7/77),明显高于未使用者[3.0%(11/368)];使用Lzd的患者对Lzd的耐药率为13.8%(11/80),明显高于未使用者[1.6%(6/365)];差异均有统计学意义(χ2值分别为12.438、6.108、26.174,P值均<0.05)。结论: 肺结核患者对Bdq、Dlm、Lzd的耐药率总体处于较低水平,但复治患者、耐多药/利福平耐药肺结核患者及使用过上述药物的患者中耐药率相对较高,用药者中的耐药率明显高于未用药者,提示在新型抗结核药物使用过程中应加强耐药监测。

关键词: 结核,肺, 微生物敏感性试验, 抗药性,细菌, 抗结核药

Abstract:

Objective: To investigate the characteristics of drug resistance to bedaquiline (Bdq), delamanid (Dlm) and linezolid (Lzd) in patients with pulmonary tuberculosis, and to provide evidence for clinicians to develop individualized treatment regimens for drug-resistant pulmonary tuberculosis cases. Methods: A retrospective study was conducted. Clinical data of 445 outpatient and inpatient pulmonary tuberculosis patients admitted to Beijing Chest Hospital, Capital Medical University from March to December 2025 were collected, including gender, age, occupation, residential area, medical history, treatment regimens and drug susceptibility testing (DST) results. DST was performed with the mycobacterial microplate drug susceptibility testing technique to determine the susceptibility of clinically isolated Mycobacterium tuberculosis strains to 16 anti-tuberculosis agents: isoniazid, rifampicin, ethambutol, Dlm, Bdq, rifabutin, levofloxacin, moxifloxacin, kanamycin, amikacin, cycloserine, protionamide, para-aminosalicylic acid, Lzd, pyrazinamide and clofazimine. We analyzed the baseline characteristics, initial/retreatment status and overall drug resistance profile of the enrolled patients, as well as the resistance rates to Bdq, Dlm and Lzd among patients with prior exposure to these drugs. Results: Among the 445 patients, the overall drug resistance rate to the 16 anti-tuberculosis drugs was 47.9% (213/445), with a rifampicin-resistant tuberculosis rate of 30.1% (134/445),a multidrug-resistant tuberculosis rate of 23.4% (104/445) and an extensively drug-resistant tuberculosis rate of 3.8% (17/445). The resistance rates to Bdq, Dlm and Lzd were 2.7% (12/445), 4.0% (18/445) and 3.8% (17/445), respectively. Retreated patients had significantly higher resistance rates to all three drugs than treatment-naive patients (Bdq: 6.4% (11/171) vs. 0.4% (1/274); Dlm: 7.0% (12/171) vs. 2.2% (6/274); Lzd: 8.8% (15/171) vs. 0.7% (2/274)), with statistically significant differences (χ2=12.552, 6.323 and 16.409, respectively; all P<0.05). The resistance rates to Bdq, Dlm and Lzd in MDR/RR-TB patients were significantly higher than those in non-rifampicin-resistant patients (Bdq: 6.7% (9/134) vs. 1.0% (3/311); Dlm: 7.5% (10/134) vs. 2.6% (8/311); Lzd: 11.9% (16/134) vs. 0.3% (1/311)), with statistically significant differences (χ2=9.717, 5.770 and 31.318, respectively; all P<0.05). Among MDR/RR-TB patients, the co-resistance rates of Bdq+Dlm, Bdq+Lzd, Dlm+Lzd and Bdq+Dlm+Lzd were 4.5% (6/134), 3.7% (5/134), 5.2% (7/134) and 3.0% (4/134), respectively. The Bdq resistance rate in patients with prior Bdq exposure was 8.4% (8/95), significantly higher than that in Bdq-naive patients (1.1% (4/350)). The Dlm resistance rate in patients with prior Dlm exposure reached 9.1% (7/77), significantly higher than that in Dlm-naive patients (3.0% (11/368)). The Lzd resistance rate in patients with prior Lzd exposure was 13.8% (11/80), significantly higher than that in Lzd-naive patients (1.6% (6/365)). All above differences were statistically significant (χ2=12.438, 6.108 and 26.174, respectively; all P<0.05). Conclusion: The overall resistance rates to Bdq, Dlm and Lzd remain relatively low in pulmonary tuberculosis patients. However, higher resistance rates are observed in retreated patients, MDR/RR-TB patients and patients with prior exposure to these new agents. The resistance rate in drug-exposed patients is significantly higher than that in drug-naive patients, indicating that drug resistance monitoring should be intensified during the clinical application of new anti-tuberculosis drugs.

Key words: Tuberculosis, pulmonary, Microbial sensitivity tests, Drug resistance, bacterial, Antitubercular agents

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