B-Pa-L/M方案治疗≥65岁老年利福平耐药肺结核患者的安全性研究

doi:10.19982/j.issn.1000-6621.20260355

中国防痨杂志 ›› 2026, Vol. 48 ›› Issue (10): 1515-1522.doi: 10.19982/j.issn.1000-6621.20260355

B-Pa-L/M方案治疗≥65岁老年利福平耐药肺结核患者的安全性研究

李荣¹, 王华², 张学珏³, 金龙⁴, 如克亚木·阿不都沙拉木⁵, 靳琇叶¹, 荆扬飞¹, 杨虹¹, 武延琴¹, 任斐¹(), 聂文娟⁶()

¹ 西安市胸科医院结核三科, 西安 710100
² 安徽省胸科医院结核科, 合肥 230061
³ 江西省胸科医院结核科, 南昌 330006
⁴ 黑龙江省传染病防治院结核内科, 哈尔滨 150500
⁵ 新疆维吾尔自治区第六人民医院结核一科, 乌鲁木齐 830011
⁶ 首都医科大学附属北京胸科医院结核科, 北京 101149

收稿日期:2026-06-16 出版日期:2026-10-10 发布日期:2026-09-30
通信作者: 任斐,Email:doc.renfei@163.com;聂文娟,Email:wenjuan.nie@outlook.com
基金资助:
陕西省科技厅重点项目(2024SF2-GJHX-64);西安市科技局医学研究一般项目(25YXYJYB00056)

Research on the safety of the B-Pa-L/M regimen in the treatment of rifampicin-resistant pulmonary tuberculosis in elderly patients (≥65 Years)

Li Rong¹, Wang Hua², Zhang Xuejue³, Jin Long⁴, Rukeyamu Abudushalamu⁵, Jin Xiuye¹, Jing Yangfei¹, Yang Hong¹, Wu Yanqin¹, Ren Fei¹(), Nie Wenjuan⁶()

¹ Third Department of Tuberculosis, Xi’an Chest Hospital, Xi’an 710100, China
² Department of Tuberculosis, Anhui Chest Hospital, Hefei 230061, China
³ Department of Tuberculosis, Jiangxi Chest Hospital, Nanchang 330006, China
⁴ Department of Tuberculosis, Heilongjiang Provincial Infectious Disease Hospital, Harbin 150500, China
⁵ First Department of Tuberculosis, The Sixth People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830011, China
⁶ Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China

Received:2026-06-16 Online:2026-10-10 Published:2026-09-30
Contact: Ren Fei, Email: doc.renfei@163.com;Nie Wenjuan, Email: wenjuan.nie@outlook.com
Supported by:
Department of Science and Technology of Shaanxi Province(2024SF2-GJHX-64);General Medical Research Project of Xi’an Science and Technology Bureau(25YXYJYB00056)

摘要/Abstract

摘要：

目的: 评估含贝达喹啉(Bdq)、普托马尼(Pa)、利奈唑胺(Lzd)和(或)莫西沙星(Mfx)的B-Pa-L/M方案治疗≥65岁老年利福平耐药肺结核(RR-PTB)患者的安全性。方法: 2025年3—11月,采用前瞻性、多中心、临床队列研究方法,参照入组标准纳入全国6家结核病定点医疗机构(包括西安市胸科医院、安徽省胸科医院、江西省胸科医院、黑龙江省传染病防治院、新疆维吾尔自治区第六人民医院、首都医科大学附属北京胸科医院)接受B-Pa-L/M方案治疗的RR-PTB患者,以65岁为界值将患者分为老年组(≥65岁)和对照组(<65岁)。收集并统计治疗期间所有不良事件(包括骨髓抑制、QTc间期延长、胃肠道反应、神经系统损伤、肝功能损伤)总发生率、3级及以上不良事件发生率及不良事件类型分布情况。结果: 参照入组标准,研究共纳入51例患者,35例(68.6%)患者发生了65例次(127.5%)不良事件,8例(15.7%)患者发生了10例次(19.6%)3级及以上不良事件。22例老年组患者中,18例(81.8%)患者发生了35例次(159.1%)不良事件,5例(22.7%)发生了7例次(31.8%)3级及以上不良事件;29例对照组患者中,17例(58.6%)患者发生了30例次(103.4%)不良事件,3例(10.3%)发生了3例次(10.3%)3级及以上不良事件,两组患者不良事件总发生率、3级及以上不良事件发生率及例次发生率的差异均无统计学意义(P值均>0.05);老年组和对照组QTc骨髓抑制、其他不良事件的发生率(例/例次)分别为5例(22.7%)和1例(3.4%)/10例次(45.5%)和4例次(13.8%)、4例(18.2%)和1例(3.4%)/4例次(18.2%)和1例次(3.4%),经Bonferroni校正,两种不良事件发生率的差异也均无统计学意义(P值均>0.004)。时间分布上,QTc间期延长及胃肠道反应主要集中在治疗后的前8周,骨髓抑制高发于9~16周,神经系统损伤集中在17~24周,且老年组与对照组患者分布规律基本一致。结论: B-Pa-L/M方案治疗老年RR-PTB患者虽各种不良事件较年轻患者发生率高,但差异均无统计学意义,总体安全性良好。临床实践中仍需针对老年患者实施强化监测策略,尤其是骨髓抑制发生情况,必要时开展治疗药物监测及个体化剂量调整,在保证疗效的前提下最大程度地降低严重不良事件风险。

关键词: 结核,肺, 老年, 利福平, 抗药性, 方案评价, B-Pa-L方案

Abstract:

Objective: To evaluate the safety of the B-Pa-L/M regimen containing bedaquiline (Bdq), pretomanid (Pa), linezolid (Lzd), and/or moxifloxacin (Mfx) in elderly patients (≥65 years) with rifampicin-resistant pulmonary tuberculosis (RR-PTB). Methods: This prospective, multicenter, clinical cohort study was conducted from March to November 2025. According to the inclusion criteria, RR-PTB patients receiving the B-Pa-L/M regimen were enrolled from six designated tuberculosis medical institutions nationwide, including Xi’an Chest Hospital, Anhui Chest Hospital, Jiangxi Chest Hospital, Heilongjiang Provincial Infectious Disease Hospital, the Sixth People’s Hospital of Xinjiang Uygur Autonomous Region, and Beijing Chest Hospital, Capital Medical University. Patients were divided into an elderly group (≥65 years) and a control group (<65 years) using age 65 as the cutoff. All adverse events (AEs) during treatment, including myelosuppression, QTc interval prolongation, gastrointestinal reactions, neurological impairment, and hepatic injury, were collected and analyzed. The overall incidence of AEs, the incidence of grade ≥3 AEs, and the distribution of AE types were calculated. Results: A total of 51 patients were enrolled. Among them, 35 patients (68.6%) experienced 65 AE episodes (127.5%), and 8 patients (15.7%) developed 10 episodes (19.6%) of grade ≥3 AEs. Among the 22 patients in the elderly group, 18 (81.8%) experienced 35 AE episodes (159.1%), and 5 (22.7%) developed 7 episodes (31.8%) of grade ≥3 AEs. Among the 29 patients in the control group, 17 (58.6%) experienced 30 AE episodes (103.4%), and 3 (10.3%) developed 3 episodes (10.3%) of grade ≥3 AEs, no statistically significant differences were observed between the two groups in the overall incidence of AEs, the incidence of grade and the episode rate ≥3 AEs (all P>0.05). The incidence rates of bone marrow suppression, and other adverse events (number of cases/frequency) in the elderly group and the control group were 5 cases (22.7%) and 1 case (3.4%) per 10 frequency (45.5%) and 4 frequency (13.8%), and 4 cases (18.2%) and 1 case (3.4%) per 4 frequency (18.2%) and 1 frequency (3.4%), respectively, after Bonferroni correction, no significant differences were found in the incidence of two AE types between the two groups (all P>0.004). Regarding temporal distribution, QTc interval prolongation and gastrointestinal reactions predominantly occurred within the first 8 weeks of treatment, myelosuppression peaked at weeks 9-16, and neurological impairment was concentrated at weeks 17-24, and the distribution patterns in the elderly group were essentially consistent with those in the control group. Conclusion: Although the incidence of various AEs was higher in elderly RR-PTB patients treated with the B-Pa-L/M regimen compared to younger patients, these differences were not statistically significant; overall, the safety profile was favorable. In clinical practice, intensified monitoring strategies should still be implemented for elderly patients, particularly regarding the occurrence of myelosuppression, and therapeutic drug monitoring along with individualized dose adjustments should be performed when necessary, so as to minimize the risk of severe AEs while ensuring treatment efficacy.

Key words: Tuberculosis, pulmonary, Aged, Rifampin, Drug resistance, Program evaluation, B-Pa-L regimen

中图分类号:

R521

李荣, 王华, 张学珏, 金龙, 如克亚木·阿不都沙拉木, 靳琇叶, 荆扬飞, 杨虹, 武延琴, 任斐, 聂文娟. B-Pa-L/M方案治疗≥65岁老年利福平耐药肺结核患者的安全性研究[J]. 中国防痨杂志, 2026, 48(10): 1515-1522. doi: 10.19982/j.issn.1000-6621.20260355

Li Rong, Wang Hua, Zhang Xuejue, Jin Long, Rukeyamu Abudushalamu, Jin Xiuye, Jing Yangfei, Yang Hong, Wu Yanqin, Ren Fei, Nie Wenjuan. Research on the safety of the B-Pa-L/M regimen in the treatment of rifampicin-resistant pulmonary tuberculosis in elderly patients (≥65 Years)[J]. Chinese Journal of Antituberculosis, 2026, 48(10): 1515-1522. doi: 10.19982/j.issn.1000-6621.20260355

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特征	对照组(29例)	老年组(22例)	χ²值	P值
性别			1.749	0.186
男性	21(72.4)	12(54.5)
女性	8(27.6)	10(45.5)
合并慢性乙型病毒性肝炎	0(0.0)	2(9.1)	-	0.181
合并冠心病	0(0.0)	11(50.0)	-	<0.001
合并糖尿病	9(31.0)	5(22.7)	-	0.510
合并其他慢性疾病^a	2(6.9)	10(45.5)	-	0.002
治疗方案			-	0.051
B-Pa-L	8(27.6)	12(54.5)
B-Pa-L/M	21(72.4)	10(45.5)

不良事件类型	对照组(29例)		老年组(22例)		χ²值	P值^a	χ²值	P值^b
不良事件类型	例(发生率,%)	例次(发生率,%)	例(发生率,%)	例次(发生率,%)	χ²值	P值^a	χ²值	P值^b
QTc间期延长	8(27.6)	8(27.6)	6(27.3)	6(27.3)	0.001	0.981	0.001	0.981
骨髓抑制	1(3.4)	4(13.8)	5(22.7)	10(45.5)	-	0.073	6.296	0.012
胃肠道反应	6(20.7)	6(20.7)	6(27.3)	7(31.8)	0.301	0.583	0.816	0.366
神经系统损伤	8(27.6)	9(31.0)	6(27.3)	6(27.3)	0.001	0.981	0.085	0.770
肝功能损伤	2(6.9)	2(6.9)	2(9.1)	2(9.1)	-	0.812	-	0.812
其他不良反应	1(3.4)	1(3.4)	4(18.2)	4(18.2)	-	0.210	-	0.210
3级及以上不良事件	3(10.3)	3(10.3)	5(22.7)	7(31.8)	-	0.268	-	0.079
合计	17(58.6)	30(103.4)	18(81.8)	35(159.1)	3.127	0.077	/	/

时间	对照组	老年组	t值	P值
基线	416.7±4.4	423.4±4.0	-1.126	0.266
4周	425.7±5.4	434.8±4.6	-1.283	0.205
8周	430.8±4.2	438.1±5.0	-1.127	0.266
12周	430.9±3.6	436.1±4.7	-0.880	0.384
16周	430.4±4.4	438.1±3.4	-1.377	0.175
20周	430.3±4.8	432.0±3.7	-0.290	0.773
24周	429.4±5.1	438.0±3.8	-1.349	0.184

不良事件类型	对照组 (29例)	老年组 (11例)	P值^a
QTc间期延长	8(27.6)	2(18.2)	0.697
骨髓抑制	1(3.4)	2(18.2)	0.170
胃肠道反应	6(20.7)	3(27.3)	1.000
神经系统损伤	8(27.6)	2(18.2)	0.697
肝功能损伤	2(6.9)	1(9.1)	1.000
其他不良反应	1(3.4)	2(18.2)	0.170
3级及以上不良事件	3(10.3)	1(9.1)	1.000

B-Pa-L/M方案治疗≥65岁老年利福平耐药肺结核患者的安全性研究

Research on the safety of the B-Pa-L/M regimen in the treatment of rifampicin-resistant pulmonary tuberculosis in elderly patients (≥65 Years)

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