超疗程应用贝达喹啉对于耐多药/利福平耐药肺结核患者的疗效及安全性临床队列分析

doi:10.19982/j.issn.1000-6621.20250372

中国防痨杂志 ›› 2026, Vol. 48 ›› Issue (3): 313-319.doi: 10.19982/j.issn.1000-6621.20250372

超疗程应用贝达喹啉对于耐多药/利福平耐药肺结核患者的疗效及安全性临床队列分析

王敬¹, 荆玮¹, 李维文², 朱庆东², 逄宇³(), 初乃惠¹(), 聂文娟¹()

¹首都医科大学附属北京胸科医院结核一科,北京 101149
²南宁市第四人民医院结核科,南宁 530023
³首都医科大学附属北京胸科医院细菌免疫室,北京 101149

收稿日期:2025-09-14 出版日期:2026-03-10 发布日期:2026-03-06
通信作者: 逄宇,初乃惠,聂文娟 E-mail:pangyupound@163.com;chunaihui1994@sina.com;wenjuan.nie@outlook.com
基金资助:
北京重大呼吸道传染病研究中心课题(BJRID2025-013);北京市医管中心扬帆3.0项目(ZLRK202331)

Clinical cohort analysis of the efficacy and safety of extended-course bedaquiline in patients with multidrug-resistant/rifampicin-resistant pulmonary tuberculosis

Wang Jing¹, Jing Wei¹, Li Weiwen², Zhu Qingdong², Pang Yu³(), Chu Naihui¹(), Nie Wenjuan¹()

¹First Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China
²Department of Tuberculosis, the Fourth People’s Hospital of Nanning, Nanning 530023, China
³Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China

Received:2025-09-14 Online:2026-03-10 Published:2026-03-06
Contact: Pang Yu,Chu Naihui,Nie Wenjuan E-mail:pangyupound@163.com;chunaihui1994@sina.com;wenjuan.nie@outlook.com
Supported by:
Beijing Major Respiratory Infectious Diseases Research Center Project(BJRID2025-013);Beijing Hospital Management Center Sail Plan 3.0 Project(ZLRK202331)

摘要/Abstract

摘要：

目的: 评价超疗程(6个月以上)应用贝达喹啉对于耐多药/利福平耐药肺结核的疗效与安全性。方法: 纳入首都医科大学附属北京胸科医院2020年1月1日至2024年1月1日就诊的耐多药/利福平耐药肺结核队列,对常规疗程(≤6个月;标准组)与延长疗程(>6个月;延长组)的含贝达喹啉联合治疗方案进行对比,统计治疗完成率和不良反应发生率,并通过多因素logistic回归分析采用Fridericia公式校正的QT间期(QTcF)>500ms的影响因素。结果: 研究纳入126例患者。其中,75例(59.5%)患者纳入标准组,51例(40.5%)患者纳入延长组。延长组及标准组均未见严重心脏不良事件。标准组良好结局率为86.7%(65/75),QTcF 450~500ms发生率为37.3%(28/75),QTcF>500ms发生率为10.7%(8/75),与延长组的88.2%(45/51)、43.1%(22/51)和9.8%(5/51)相比,差异均无统计学意义(χ²=0.043,P=0.835;χ²=1.851,P=0.173;χ²=0.414,P=0.521)。多因素logistic回归分析显示,既往心脏病病史(OR=6.50,95%CI:1.52~27.80)是QTcF延长(>500ms)的危险因素。结论: 对于耐多药/利福平耐药肺结核患者,延长疗程使用贝达喹啉总体疗效与安全性良好,未观察到严重不良事件风险的增加。

关键词: 结核, 贝达喹啉, 药物毒性, 治疗结果, 因素分析,统计学

Abstract:

Objective: To evaluate the efficacy and safety of extended-course (>6 months) bedaquiline-containing regimens in the treatment of multidrug-resistant/rifampin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: Patients with MDR/RR-PTB treated at Beijing Chest Hospital, Capital Medical University, between January 1, 2020 and January 1, 2024 were included in this cohort study. Outcomes were compared between patients receiving a standard course (≤6 months) and those receiving an extended course (>6 months) of bedaquiline-containing combination regimens. The treatment completion rate and the incidence of adverse events were recorded. Multivariable logistic regression was used to analyze factors associated with a Fridericia-corrected QT interval (QTcF) >500 ms. Results: A total of 126 patients were included in the study. Among them, 75 patients (59.5%) were assigned to the standard group, while 51 patients (40.5%) were assigned to the extended group. No serious cardiac adverse events were observed in either the standard-course or extended-course group. There was no statistically significant difference between the two groups in the proportion of favorable treatment outcomes (standard vs. extended: 86.7% (65/75) vs. 88.2% (45/51)), the difference was statistically significant (χ²=0.043, P=0.835). Likewise, the incidences of QTcF 450-500 ms (standard vs. extended: 37.3% (28/75) vs. 43.1% (22/51)) and QTcF >500 ms (standard vs. extended: 10.7% (8/75) vs. 9.8% (5/51)) did not differ significantly between the two groups (χ²=1.851, P=0.173; χ²=0.414, P=0.521). Multivariable analysis showed that a history of cardiac disease (OR=6.50, 95%CI: 1.52-27.80) was risk factor for QTcF prolongation (>500 ms). Conclusion: For patients with multidrug-resistant/rifampicin-resistant pulmonary tuberculosis, extended-course use of bedaquiline demonstrates good overall efficacy and safety, with no observed increase in the risk of serious adverse events.

Key words: Tuberculosis, Bedaquiline, Drug toxicity, Treatment outcomes, Factor analysis, statistical

中图分类号:

R521
R453

王敬, 荆玮, 李维文, 朱庆东, 逄宇, 初乃惠, 聂文娟. 超疗程应用贝达喹啉对于耐多药/利福平耐药肺结核患者的疗效及安全性临床队列分析[J]. 中国防痨杂志, 2026, 48(3): 313-319. doi: 10.19982/j.issn.1000-6621.20250372

Wang Jing, Jing Wei, Li Weiwen, Zhu Qingdong, Pang Yu, Chu Naihui, Nie Wenjuan. Clinical cohort analysis of the efficacy and safety of extended-course bedaquiline in patients with multidrug-resistant/rifampicin-resistant pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2026, 48(3): 313-319. doi: 10.19982/j.issn.1000-6621.20250372

图/表 5

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参考文献 19

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临床特征	标准组(75例)	延长组(51例)	统计检验值	P值
年龄(岁, $\bar{x}±s$)	37.5±15.5	34.5±13.2	t=1.170	0.321
性别[例(构成比,%)]			χ²=0.252	0.616
男性	47(62.7)	30(58.8)
女性	28(37.3)	21(41.2)
既往治疗史[例(构成比,%)]			χ²=0.105	0.746
有	51(68.0)	36(70.6)
无	24(32.0)	15(29.4)
吸烟史[例(构成比,%)]			χ²=0.090	0.764
有	26(34.7)	19(37.3)
无	49(65.3)	32(62.7)
饮酒史[例(构成比,%)]			χ²=0.375	0.540
有	23(30.7)	18(35.3)
无	52(69.3)	33(64.7)
心脏病病史[例(构成比,%)]			χ²=0.028	1.000
有	5(6.7)	3(5.9)
无	70(93.3)	48(94.1)
合并抗结核药物[例(合并治疗率,%)]
德拉马尼	14(18.7)	10(19.6)	χ²=0.016	0.900
氯法齐明	70(93.3)	45(88.2)	χ²=0.744	0.388
莫西沙星	24(32.0)	12(23.5)	χ²=1.115	0.291
左氧氟沙星	30(40.0)	14(27.5)	χ²=2.484	0.115

治疗结局	标准组(75例)	延长组(51例)	χ²值	P值
良好结局	65(86.7)	45(88.2)	0.043	0.835
治愈	55(73.3)	35(68.6)	0.329	0.566
完成治疗	10(13.3)	10(19.6)	0.878	0.349
不良结局	10(13.3)	6(11.8)	0.043	0.835
治疗失败	6(8.0)	4(7.8)	0.001	1.000
失访	3(4.0)	1(2.0)	0.411	0.521
死亡	1(1.3)	1(2.0)	0.014	1.000

不良反应	标准组(75例)	延长组(51例)	χ²值	P值
QTcF>500ms	8(10.7)	5(9.8)	0.414	0.521
QTcF 450~500ms	28(37.3)	22(43.1)	1.851	0.173
肝功能异常	25(33.3)	13(25.5)	1.370	0.243
消化道反应	11(14.7)	7(13.7)	0.001	0.972
周围神经病变	8(10.7)	4(7.8)	0.061	0.807
心肌酶异常	1(1.3)	0(0.0)	0.993	0.411

因素	QTcF>500ms (13例)	QTcF≤500ms (113例)	β值	s $\bar{x}$值	Wald χ²值	OR值	95%CI值	P值
性别[例(构成比,%)]
男性	8(61.5)	69(61.1)	1.00
女性	5(38.5)	44(38.9)	0.03	0.57	0.00	1.03	0.34~3.09	0.956
年龄组[例(构成比,%)]
18~44岁	8(61.5)	80(70.8)	1.00
45~59岁	4(30.8)	23(20.4)	0.53	0.63	0.72	1.70	0.49~5.89	0.397
≥60岁	1(7.7)	10(8.8)	―0.09	1.09	0.01	0.91	0.10~8.53	0.934
治疗史[例(构成比,%)]
初治	2(15.4)	37(32.7)	1.00
复治	11(84.6)	76(67.3)	0.73	0.77	0.90	2.07	0.46~9.29	0.343
心脏病病史[例(构成比,%)]
无	9(69.2)	109(96.5)	1.00
有	4(30.8)	4(3.5)	1.87	0.74	6.41	6.50	1.52~27.80	0.011
应用贝达喹啉时间[例(构成比,%)]
标准组	8(61.5)	67(59.3)	1.00
延长组	5(38.5)	46(40.7)	0.07	0.59	0.01	1.07	0.34~3.32	0.900
合并用药[例(构成比,%)]
德拉马尼
无	12(92.3)	80(70.8)	1.00
有	1(7.7)	33(29.2)	―1.60	1.04	2.39	0.20	0.03~1.52	0.122
左氧氟沙星
无	7(53.8)	75(66.4)	1.00
有	6(46.2)	38(33.6)	0.36	0.60	0.36	1.44	0.44~4.68	0.547
莫西沙星
无	7(53.8)	83(73.5)	1.00
有	6(46.2)	30(26.5)	0.65	0.60	1.17	1.91	0.59~6.15	0.280
氯法齐明
无	1(7.7)	11(9.7)	1.00
有	12(92.3)	102(90.3)	0.25	1.09	0.05	1.29	0.15~10.80	0.820

超疗程应用贝达喹啉对于耐多药/利福平耐药肺结核患者的疗效及安全性临床队列分析

Clinical cohort analysis of the efficacy and safety of extended-course bedaquiline in patients with multidrug-resistant/rifampicin-resistant pulmonary tuberculosis

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