6个月B-Pa-L/M短程方案与18个月含贝达喹啉长程方案治疗利福平耐药肺结核的有效性与安全性评价

doi:10.19982/j.issn.1000-6621.20260361

摘要/Abstract

摘要：

目的: 评价6个月B-Pa-L/M(B:贝达喹啉;Pa:普托马尼;L:利奈唑胺;M:莫西沙星)短程方案与18个月含贝达喹啉(Bdq)长程全口服方案治疗利福平耐药肺结核(RR-PTB)患者的临床疗效及安全性,为6B-Pa-L/M短程方案的应用提供真实世界数据。方法: 采用回顾性研究方法,参照入组标准纳入安徽省和新疆维吾尔自治区142例RR-PTB患者,其中66例使用6B-Pa-L/M短程方案治疗(B-Pa-L/M组),76例使用18个月含Bdq全口服长程方案治疗(长程组)。通过综合临床疗效、痰菌阴转情况及治疗过程中药物相关不良反应发生情况评估两种治疗方案的有效性和安全性。结果: B-Pa-L/M组治疗成功率[96.97%(64/66)]明显高于长程组[82.89%(63/76)],差异有统计学意义(χ²=7.407,P=0.006)。92例基线痰培养阳性患者中,B-Pa-L/M组在治疗4、8、12及16周时痰菌阴转率[分别为59.09%(26/44)、84.09%(37/44)、93.18%(41/44)、95.45%(42/44)]均明显高于长程组[分别为27.08%(13/48)、43.75%(21/48)、70.83%(34/48)、79.17%(38/48)],差异均有统计学意义(χ²=9.630,P=0.002;χ²=16.035,P<0.001;χ²=7.611,P=0.006;χ²=5.370,P=0.020)。Kaplan-Meier生存分析显示,B-Pa-L/M组的痰菌阴转时间[4(4,8)周]明显短于长程组[12(4,16)周],差异有统计学意义(log-rank检验,χ²=12.936,P<0.001)。B-Pa-L/M组总体不良反应、胃肠道反应、精神症状发生率[分别为45.45%(30/66)、7.58%(5/66)、0(0/66) ]均明显低于长程组[分别为68.42%(52/76)、21.05%(16/76)、14.47%(11/76)],差异均有统计学意义(χ²=7.636,P=0.006;χ²=5.091,P=0.024;Fisher精确概率法,P=0.001);但3级及以上不良事件[6.06%(4/66)]与长程组[10.53%(8/76)]的差异无统计学意义(χ²=0.905,P=0.341)。结论: B-Pa-L/M短程方案治疗RR-PTB可更快实现痰菌阴转,治疗成功率高于含Bdq长程全口服方案,且安全性良好。

关键词: 结核,肺, 抗药性, 对比研究, 方案评价, 普托马尼, 贝达喹啉

Abstract:

Objective: To evaluate clinical effectiveness and safety of 6-month B-Pa-L/M short-course regimen compared with 18-month long-course all-oral regimen containing bedaquiline (Bdq) on patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB), to provide real-world evidence for the application of 6B-Pa-L/M short-course regimen. Methods: A retrospective study was conducted, enrolling 142 patients with RR-PTB from Anhui Province and Xinjiang Uygur Autonomous Region. Among them, 66 received 6B-Pa-L/M short-course regimen (B-Pa-L/M group), and 76 received 18-month all-oral long-course regimen containing Bdq (long-course group). The efficacy and safety of the two regimens was assessed by sputum culture conversion rate, comprehensive clinical effectiveness, and adverse drug reactions during treatment. Results: The treatment success rate of B-Pa-L/M group (96.97%, 64/66) was significantly higher than that of the long-course group (82.89%, 63/76; χ²=7.407, P=0.006). Among the 92 patients with positive baseline sputum cultures, the sputum conversion rates of B-Pa-L/M group at 4, 8, 12, and 16 weeks were significantly higher than those of the long-course group (4 weeks: 59.09% (26/44) vs. 27.08% (13/48), χ²=9.630, P=0.002; 8 weeks: 84.09% (37/44) vs. 43.75% (21/48), χ²=16.035, P<0.001; 12 weeks: 93.18% (41/44) vs. 70.83% (34/48), χ²=7.611, P=0.006; 16 weeks: 95.45% (42/44) vs. 79.17% (38/48), χ²=5.370, P=0.020). Kaplan-Meier analysis showed that the median time to sputum culture conversion of B-Pa-L/M group (4 (4, 8) weeks) was significantly shorter than that of the long-course group (12 (4, 16) weeks; log-rank χ²=12.936, P<0.001). In terms of safety, the overall incidence of adverse reactions, gastrointestinal adverse reactions, and psychiatric symptoms of B-Pa-L/M group (specifically 45.45% (30/66), 7.58% (5/66), and 0 (0/66), respectively) were significantly lower than those of long-course group (specifically 68.42% (52/76), 21.05% (16/76), and 14.47% (11/76), respectively), all differences were statistically significant (χ²=7.636, P=0.006; χ²=5.091, P=0.024; Fisher’s exact test, P=0.001). However, compared with that in the long-term group, the difference in the incidence of adverse events rated as grade 3 or higher (6.06% (4/66) vs. 10.53% (8/76)) was not statistically significant (χ²=0.905, P=0.341). Conclusion: The B-Pa-L/M short-course regimen achieves faster sputum culture conversion in the treatment of RR-PTB. The treatment success rate is higher than that of the long-course all-oral regimen containing Bdq, and the regimen demonstrated a favorable safety profile.

Key words: Tuberculosis, pulmonary, Drug resistance, Comparative study, Program evaluation, Pretomanid, Bedaquiline

中图分类号:

R521

黄鹏飞, 肖雨, 彭溢, 熊延军, 郭珊珊, 娜地拉·阿布里孜, 玛力帕提·艾尔肯江, 王华, 如克亚木·阿不都沙拉木. 6个月B-Pa-L/M短程方案与18个月含贝达喹啉长程方案治疗利福平耐药肺结核的有效性与安全性评价[J]. 中国防痨杂志, 2026, 48(10): 1506-1514. doi: 10.19982/j.issn.1000-6621.20260361

Huang Pengfei, Xiao Yu, Peng Yi, Xiong Yanjun, Guo Shanshan, Nadila Abulizi, Malipati Aierkenjiang, Wang Hua, Rukeyamu Abudushalamu. Efficacy and safety of 6-month short-course regimen B-Pa-L/M versus 18-month long-course regimen for treating rifampicin-resistant pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2026, 48(10): 1506-1514. doi: 10.19982/j.issn.1000-6621.20260361

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药物	体质量
药物	<50kg	≥50kg
利奈唑胺(Lzd)	600mg,1次/d
贝达喹啉(Bdq)	400mg,1次/d,前2周;200mg,3次/周
左氧氟沙星(Lfx)	600mg,1次/d	800mg,1次/d
莫西沙星(Mfx)	400mg,1次/d
氯法齐明(Cfz)	100mg,1次/d
环丝氨酸(Cs)	早250mg,晚250mg	早250mg,晚500mg
普托马尼(Pa)	200mg,1次/d
乙胺丁醇(E)	750mg,1次/d	1000mg,1次/d
吡嗪酰胺(Z)	500mg,3次/d
丙硫异烟胺(Pto)	200mg,3次/d
对氨基水杨酸(PAS)	2000mg,4次/d

特征	B-Pa-L/M组(66例)	长程组(76例)	统计检验值	P值
年龄[岁,M(Q₁,Q₃)]	41(25,63)	33(26,57)	Z=1.133	0.260
性别[例(构成比,%)]			χ²=1.210	0.271
女性	33(50.00)	31(40.79)
男性	33(50.00)	45(59.21)
BMI[例(构成比,%)]			χ²=0.136	0.934
<18.5kg/m²	17(25.76)	21(27.63)
18.5~24kg/m²	40(60.61)	46(60.53)
>24kg/m²	9(13.63)	9(11.84)
耐药类型[例(构成比,%)]			χ²=0.328	0.826
RR-TB	3(4.55)	2(2.63)
MDR-TB	39(59.10)	46(60.52)
pre-XDR-TB	24(36.35)	28(36.85)
病灶累及数[例(构成比,%)]			χ²=0.211	0.646
1~2个	50(75.76)	55(72.39)
≥3个	16(24.24)	21(27.61)
空洞[例(构成比,%)]			χ²=0.007	0.932
无	36(54.55)	42(55.26)
有	30(45.45)	34(44.74)
肺外结核[例(发生率,%)]			-	0.658
结核性胸膜炎	3(4.55)	2(2.63)
淋巴结结核	2(3.03)	1(1.32)
结核性心包炎	0(0.00)	1(1.32)
疾病类型[例(构成比,%)]			χ²=0.000	1.000
初治	33(50.00)	38(50.00)
复治	33(50.00)	38(50.00)
吸烟史[例(构成比,%)]			χ²=0.312	0.577
无	60(90.91)	71(93.42)
有	6(9.09)	5(6.58)
饮酒史[例(构成比,%)]			-	0.663
无	63(95.45)	74(97.37)
有	3(4.55)	2(2.63)
合并症[例(发生率,%)]
高血压	8(12.12)	3(3.95)	χ²=3.302	0.069
糖尿病	9(13.64)	9(11.84)	χ²=0.103	0.749
乙型病毒性肝炎	4(6.06)	3(3.95)	-	0.704
支气管扩张	3(4.55)	2(2.63)	-	0.663
长期服用免疫抑制剂	1(1.52)	0(0.00)	-	0.465
恶性肿瘤	1(1.52)	1(1.32)	-	1.000
痰培养[例(构成比,%)]			χ²=0.191	0.662
阳性	44(66.67)	48(63.16)
阴性	22(33.33)	28(36.84)
痰涂片[例(构成比,%)]			χ²=0.018	0.894
阳性	32(48.48)	36(47.37)
阴性	34(51.52)	40(52.63)

治疗时间	B-Pa-L/M组 (66例)	长程组 (76例)	χ²值	P值	治疗时间	B-Pa-L/M组 (66例)	长程组 (76例)	χ²值	P值
4周			9.630	0.002	16周			5.370	0.020
阴性	26(59.09)	13(27.08)			阴性	42(95.45)	38(79.17)
阳性	18(40.91)	35(72.92)			阳性	2(4.55)	10(20.83)
8周			16.035	<0.001	20周			-	0.093
阴性	37(84.09)	21(43.75)			阴性	42(95.45)	40(83.33)
阳性	7(15.91)	27(56.25)			阳性	2(4.55)	8(16.67)
12周			7.611	0.006	24周			-	0.093
阴性	41(93.18)	34(70.83)			阴性	42(95.45)	40(83.33)
阳性	3(6.82)	14(29.17)			阳性	2(4.55)	8(16.67)

不良反应	B-Pa-L/M组 (66例)	长程组 (76例)	χ²值	P值	不良反应	B-Pa-L/M组 (66例)	长程组 (76例)	χ²值	P值
骨髓抑制			1.117	0.291	胃肠道反应			5.091	0.024
有	14(21.21)	22(28.95)			有	5(7.58)	16(21.05)
无	52(78.79)	54(71.05)			无	61(92.42)	60(78.95)
周围神经炎			0.449	0.503	QTcF延长			0.370	0.543
有	15(22.73)	21(27.63)			有	5(7.58)	8(10.53)
无	51(77.27)	55(72.37)			无	61(92.42)	68(89.47)
视神经炎			-	0.632	精神症状			10.355	0.001
有	1(1.52)	3(3.95)			有	0(0.00)	11(14.47)
无	65(98.48)	73(96.05)			无	66(100.00)	65(85.53)
肝功能损伤			0.345	0.557	总体不良反应			7.636	0.006
有	11(16.67)	10(13.16)			有	30(45.45)	52(68.42)
无	55(83.33)	66(86.84)			无	36(54.55)	24(31.58)
肾功能损伤			-	1.000	≥3级不良事件			0.905	0.341
有	4(6.06)	4(5.26)			有	4(6.06)	8(10.53)
无	62(93.94)	72(94.74)			无	62(93.94)	66(89.47)