Safety analysis of the B-Pa-L/M regimen for rifampicin-resistant pulmonary tuberculosis

doi:10.19982/j.issn.1000-6621.20260364

Abstract

Abstract:

Objective: To evaluate the safety of the B-Pa-L/M regimen in patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB) and to assess its effectiveness in real-world clinical practice in China based on preliminary treatment outcomes. Methods: A multicenter real-world observational study was conducted among patients with RR-PTB who received the B-Pa-L/M regimen at six designated tuberculosis hospitals in Jiangsu Province, between April and August 2025. Baseline characteristics and follow-up data, including clinical manifestations, laboratory findings, electrocardiographic examinations, and radiological assessments, were collected. Adverse events (AEs) were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events (CTCAE) issued by the U.S. National Cancer Institute. The incidence, severity, and management of AEs were analyzed, and bacteriological conversion and treatment outcomes were evaluated. Results: A total of 51 patients were enrolled, of whom one withdrew from treatment during the early treatment phase because of severe gastrointestinal adverse reactions, whereas the remaining patients continued treatment according to the planned regimen. Grade ≥3 AEs occurred in six patients (12.0%). Hematologic toxicity, Fridericia-corrected QT interval (QTcF) prolongation, and liver function abnormalities were the most common AEs, occurring in 46.0% (23/50), 34.0% (17/50), and 32.0% (16/50) of patients, respectively. During treatment, 14 patients (28.0%, 14/50) required treatment modification because of AEs, including dose reduction in four patients, temporary drug interruption in eight, and drug substitution in one; only one patient withdrew from treatment because of severe gastrointestinal toxicity. Among the 98 AE episodes recorded during treatment, 90.8% (89/98) resolved following dose adjustment, temporary drug interruption, or supportive treatment, whereas 9.2% (9/98) resulted in permanent discontinuation of the implicated drug or withdrawal from treatment. The overall treatment success rate was 92.0% (46/50). At the end of month 2, the sputum smear and culture conversion rates were 90.6% (29/32) and 100.0% (36/36), respectively. Conclusion: The B-Pa-L/M regimen demonstrated favorable clinical effectiveness and a manageable safety profile in patients with RR-PTB. Although AEs were common, most were mild to moderate and could be effectively managed through active safety monitoring and individualized interventions, enabling most patients to complete treatment and achieve a high treatment success rate.

Key words: Tuberculosis, Rifampicin, Drug resistance, Adverse drug reaction, Treatment outcome

CLC Number:

R521

Jiang Wenxin, Zhang Xiangrong, Tang Peijun, Qin Zhihua, Gao Chunjing, Zhang She, Zhao Xinguo, Zhu Limei, Liu Qiao. Safety analysis of the B-Pa-L/M regimen for rifampicin-resistant pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2026, 48(10): 1487-1496. doi: 10.19982/j.issn.1000-6621.20260364

Figures/Tables 7

References 37

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特征	例数	构成比(%)
低体质量指数(<18.5kg/m²)^a(%)	13	26.0
性别
男性	39	78.0
女性	11	22.0
吸烟史^a	26	52.0
饮酒史^a	25	50.0
合并糖尿病^a	11	22.0
合并高血压^a	10	20.0
入组方案
B-Pa-L	12	24.0
B-Pa-L-M	38	76.0
耐药类型
RR-PTB	19	38.0
MDR-PTB	19	38.0
pre-XDR-PTB	12	24.0
患者分类
新患者	30	60.0
复发患者	11	22.0
治疗失败患者	9	18.0
基线痰涂片阳性^a	32	64.0
基线痰培养阳性^a	36	72.0

指标	例数	发生率(%)
发生≥3级不良事件	6	12.0
因不良反应进行药物调整	14	28.0
因不良反应药物减量	4	8.0
因不良反应更换药物	1	2.0
因不良反应停用药物	8	16.0
因不良反应退组	1	2.0

不良事件	合计	1~2级	≥3级
QTcF延长	17(34.0)	16(32.0)	1(2.0)
白细胞减少	11(22.0)	10(20.0)	1(2.0)
贫血	17(34.0)	15(30.0)	2(4.0)
血小板减少	9(18.0)	9(18.0)	0(0.0)
恶心	8(16.0)	8(16.0)	0(0.0)
呕吐	3(6.0)	3(6.0)	0(0.0)
胃痛	3(6.0)	3(6.0)	0(0.0)
头晕	1(2.0)	1(2.0)	0(0.0)
周围神经病变	3(6.0)	3(6.0)	0(0.0)
视物模糊	1(2.0)	1(2.0)	0(0.0)
ALT升高	15(30.0)	13(26.0)	2(4.0)
AST升高	10(20.0)	9(18.0)	1(2.0)

不良事件分类	包含的具体不良事件	例数	发生率 (%)
血液学毒性	贫血、白细胞减少、血小板减少	23	46.0
QTcF延长	QTcF延长	17	34.0
肝功能异常	ALT升高、AST升高	16	32.0
胃肠道反应	恶心、呕吐、胃痛、胃肠道不适	9	18.0
神经系统损伤	周围神经病变、视物模糊、头晕	5	10.0

不良反应类型	调整药物	调整方式	例数
胃肠道反应	莫西沙星	停药	3
胃肠道反应	未说明	退组	1
胃肠道反应	未说明	自行停药/治疗中断	1
肝功能损伤	莫西沙星	换药 (改用左氧氟沙星)	1
肝功能损伤	莫西沙星	停药	1
头晕	莫西沙星	停药	1
QTcF间期延长	莫西沙星	停药	1
血细胞减少	利奈唑胺	减量	3
血细胞减少	利奈唑胺	停药	1
视物模糊	利奈唑胺	减量	1
双下肢麻木	利奈唑胺	减量	1
脚麻	利奈唑胺	停药	1