B-Pa-L/M与B-D-L-Lfx/C方案治疗利福平耐药肺结核的有效性和安全性研究

doi:10.19982/j.issn.1000-6621.20260363

摘要/Abstract

摘要：

目的: 比较B-Pa-L/M(B:贝达喹啉;Pa:普托马尼;L:利奈唑胺;M:莫西沙星)与B-D-L-Lfx/C(D:德拉马尼;Lfx:左氧氟沙星;C:氯法齐明)两种短程方案在利福平耐药肺结核患者中的疗效与安全性,为优化临床治疗方案提供依据。方法: 采用随机、多中心研究设计,选取2024年8月至2025年8月期间于安徽省胸科医院与云南省传染病医院诊治的90例利福平耐药肺结核患者,按随机数字表法以1∶2比例分为B-Pa-L/M组(30例)和B-D-L-Lfx/C组(60例)。比较两组患者治疗期间各随访时间点的痰菌阴转率及中位阴转时间;同时观察并记录治疗过程中发生的不良事件,比较两组不良事件发生率,以评估方案的安全性。结果: 两组患者在治疗4、8、16、24周时痰菌阴转率比较,差异均无统计学意义(P值均>0.05);治疗12周时,B-Pa-L/M组痰菌阴转率(96.67%,29/30)高于B-D-L-Lfx/C组(80.00%,48/60),差异有统计学意义(χ²=4.495,P=0.034)。治疗24周时,两组均达到较高痰菌阴转率,B-Pa-L/M组为96.67%(29/30),B-D-L-Lfx/C组为91.67% (55/60)。B-Pa-L/M组痰菌中位转阴时间为4周,短于B-D-L-Lfx/C组的8周,差异有统计学意义(Log-rank χ²=4.063,P=0.044)。安全性结果显示,B-Pa-L/M组患者头痛未发生,B-D-L-Lfx/C组患者头痛的发生率为21.67%(13/60),差异有统计学意义(Fisher确切概率法,P=0.004)。结论: B-Pa-L/M与B-D-L-Lfx/C两种短程方案均具有较好的有效性与安全性。与B-D-L-Lfx/C方案相比,B-Pa-L/M方案在治疗中期表现出更优的痰菌清除效果,且头痛发生率更低,提示其具有更好的中期疗效及神经系统耐受性。

关键词: 结核, 抗药性, 治疗结果, 药物毒性, 普托马尼, 德拉马尼

Abstract:

Objective: To compare the efficacy and safety of two short-course regimens, B-Pa-L/M and B-D-L-Lfx/C, in patients with rifampicin-resistant pulmonary tuberculosis, and to provide evidence for optimizing clinical treatment strategies. Methods: A randomized, multicenter study was conducted. A total of 90 patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB) treated at two sites in Anhui Chest Hospital and Yunnan Provincial Infectious Disease Hospital between August 2024 and August 2025 were enrolled. Using a random number table, patients were allocated in a 1∶2 ratio into a B-Pa-L/M group (30 cases) and a B-D-L-Lfx/C group (60 cases). The sputum Mycobacterium tuberculosis culture conversion rate was used as the primary efficacy endpoint. The sputum culture conversion rates at each follow-up time point during treatment and the median time to conversion were compared between the two groups. In parallel, all adverse events (AEs) occurring during treatment were observed and recorded, and the incidence of AEs was compared between the two groups to evaluate the safety of the regimens. Results: No statistically significant differences were observed between the two groups in sputum culture conversion rates at weeks 4, 8, 16, or 24 (all Ps>0.05). At week 12, the sputum culture conversion rate in the B-Pa-L/M group (96.67%, 29/30) was significantly higher than that in the B-D-L-Lfx/C group (80.00%, 48/60)(χ²=4.495,P=0.034). At week 24, both groups achieved high sputum culture conversion rates: 96.67% (29/30) in the B-Pa-L/M group and 91.67% (55/60) in the B-D-L-Lfx/C group. The median time to sputum culture conversion was significantly shorter in the B-Pa-L/M group (4 weeks) than in the B-D-L-Lfx/C group (8 weeks)(log-rank χ²=4.063, P=0.044). Safety results showed that the incidence of headache in the B-Pa-L/M group was 0/30 (0%), which was significantly lower than that in the B-D-L-Lfx/C group (13/60, 21.67%), and the difference was statistically significant (Fisher’s exact test, P=0.004). Conclusion: Both the B-Pa-L/M and B-D-L-Lfx/C short-course regimens demonstrate favorable efficacy and safety in the treatment of rifampicin-resistant pulmonary tuberculosis. Compared with the B-D-L-Lfx/C regimen, the B-Pa-L/M regimen exhibits superior mid-term mycobacterial clearance and a lower incidence of headache, suggesting better intermediate efficacy and neurological tolerability.

Key words: Tuberculosis, Drug resistance, Treatment outcome, Drug toxicity, Pretomanid, Delamanid

中图分类号:

韩伊, 肖雨, 孔维金, 林榕, 楼金成, 熊延军, 王华, 张云桂. B-Pa-L/M与B-D-L-Lfx/C方案治疗利福平耐药肺结核的有效性和安全性研究[J]. 中国防痨杂志, 2026, 48(10): 1497-1505. doi: 10.19982/j.issn.1000-6621.20260363

Han Yi, Xiao Yu, Kong Weijin, Lin Rong, Lou Jincheng, Xiong Yanjun, Wang Hua, Zhang Yungui. Evaluate the efficacy and safety of the B-Pa-L/M and B-D-L-Lfx/C regimens for the treatment of rifampicin-resistant pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2026, 48(10): 1497-1505. doi: 10.19982/j.issn.1000-6621.20260363

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药物	体质量<50kg	体质量≥50kg
利奈唑胺	600mg,1次/d
贝达喹啉	400mg,1次/d,前2周;200mg,3次/周
左氧氟沙星	600mg,1次/d	800mg,1次/d
莫西沙星	400mg,1次/d
氯法齐明	100mg,1次/d
德拉马尼	100mg,2次/d
普托马尼	200mg,1次/d

特征	B-Pa-L/M(30例)	B-D-L-Lfx/C(60例)	统计检验值	P值
年龄[岁,M(Q₁,Q₃)]	41.00(25.75,62.50)	39.50(28.00,53.00)	Z=-0.724	0.469
性别[例(构成比,%)]			χ²=0.094	0.760
女性	11(36.67)	24(40.00)
男性	19(63.33)	36(60.00)
BMI[例(构成比,%)]			χ²=0.540	0.763
<18.5kg/m²	12(40.00)	20(33.33)
18.5~24kg/m²	16(53.33)	34(56.67)
>24kg/m²	2(6.67)	6(10.00)
耐药类型[例(构成比,%)]			χ²=0.028	0.986
RR-TB	10(33.33)	21(35.00)
MDR-TB	14(46.67)	27(45.00)
pre-XDR-TB	6(20.00)	12(20.00)
肺部病灶[例(构成比,%)]			χ²=2.516	0.113
单侧	4(13.33)	17(28.33)
双侧	26(86.67)	43(71.67)
肺部病灶空洞[例(构成比,%)]			χ²=0.090	0.765
无	17(56.67)	32(53.33)
有	13(43.33)	28(46.67)
肺外结核[例(构成比,%)]			-	1.000
无	28(93.33)	55(91.67)
有	2(6.67)	5(8.33)
患者类型[例(构成比,%)]			χ²=2.860	0.091
初治	15(50.00)	41(68.33)
复治	15(50.00)	19(31.67)
吸烟史[例(构成比,%)]			χ²=0.028	0.868
无	22(73.33)	43(71.67)
有	8(26.67)	17(28.33)
饮酒史[例(构成比,%)]			χ²=2.057	0.151
无	26(86.67)	44(73.33)
有	4(13.33)	16(26.67)
高血压[例(构成比,%)]			-	1.000
无	27(90.00)	54(90.00)
有	3(10.00)	6(10.00)
糖尿病[例(构成比,%)]			-	1.000
无	28(93.33)	55(91.67)
有	2(6.67)	5(8.33)

治疗时间	B-Pa-L/M(30例)	B-D-L-Lfx/C(60例)	统计检验值	P值
4周			χ²=1.800	0.180
阴性	18(60.00)	27(45.00)
阳性	12(40.00)	33(55.00)
8周			χ²=1.474	0.225
阴性	25(83.33)	43(71.67)
阳性	5(16.67)	17(28.33)
12周			χ²=4.495	0.034
阴性	29(96.67)	48(80.00)
阳性	1(3.33)	12(20.00)
16周			-	0.262
阴性	29(96.67)	52(86.67)
阳性	1(3.33)	8(13.33)
20周			-	0.417
阴性	29(96.67)	54(90.00)
阳性	1(3.33)	6(10.00)
24周			-	0.659
阴性	29(96.67)	55(91.67)
阳性	1(3.33)	5(8.33)

不良反应类型	B-Pa-L/M(30例)	B-D-L-Lfx/C(60例)	统计检验值	P值
骨髓抑制			χ²=0.360	0.549
有	6(20.00)	9(15.00)
无	24(80.00)	51(85.00)
周围神经炎			-	0.767
有	4(13.33)	10(16.67)
无	26(86.67)	50(83.33)
视神经炎			-	0.551
有	0(0.00)	2(3.33)
无	30(100.00)	58(96.67)
肝功能损伤			-	0.433
有	4(13.33)	4(6.67)
无	26(86.67)	56(93.33)
肾功能损伤			-	0.257
有	2(6.67)	1(1.67)
无	28(93.33)	59(98.33)
胃肠道反应			χ²=0.950	0.330
有	7(23.33)	9(15.00)
无	23(76.67)	51(85.00)
QTcF延长			-	0.129
有	2(6.67)	12(20.00)
无	28(93.33)	48(80.00)
失眠			-	0.173
有	0(0.00)	6(10.00)
无	30(100.00)	54(90.00)
头痛			-	0.004
有	0(0.00)	13(21.67)
无	30(100.00)	47(78.33)
发生不良事件的患者			χ²=1.440	0.230
有	14(46.67)	36(60.00)
无	16(53.33)	24(40.00)

AE分级	B-Pa-L/M组						B-D-L-Lfx/C组
AE分级	合计	1级	2级	3级	4级	5级	合计	1级	2级	3级	4级	5级
骨髓抑制	6	4	2	0	0	0	9	5	4	0	0	0
周围神经炎	4	3	1	0	0	0	10	8	2	0	0	0
视神经炎	0	0	0	0	0	0	2	2	0	0	0	0
肝功能损伤	4	2	2	0	0	0	4	3	1	0	0	0
肾功能损伤	2	1	1	0	0	0	1	1	0	0	0	0
胃肠道反应	7	3	4	0	0	0	9	6	3	0	0	0
QTcF延长	2	1	1	0	0	0	12	10	2	0	0	0
失眠	0	0	0	0	0	0	6	4	2	0	0	0
头痛	0	0	0	0	0	0	13	9	4	0	0	0