首次复治敏感肺结核治疗新方案疗效的验证性研究

doi:10.19982/j.issn.1000-6621.20230192

中国防痨杂志 ›› 2023, Vol. 45 ›› Issue (11): 1078-1083.doi: 10.19982/j.issn.1000-6621.20230192

首次复治敏感肺结核治疗新方案疗效的验证性研究

戈启萍¹, 张立杰², 黄学锐¹, 姜广路³, 韩喜琴⁴, 王敬萍⁵, 杜建²(), 马艳⁶(), 高微微²()

¹首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所结核二科,北京 101149
²首都医科大学附属北京胸科医院/中国疾病预防控制中心结核病防治临床中心,北京 101149
³首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所/国家结核病临床实验室/北京市耐药结核病研究重点实验室,北京 101149
⁴首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所结核三科,北京 101149
⁵首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所门诊部,北京 101149
⁶中国中医科学院中医临床基础医学研究所感染性疾病防治科,北京 100700

收稿日期:2023-06-04 出版日期:2023-11-10 发布日期:2023-11-03
通信作者: 杜建, Email: jdu-sdu@163.com; 马艳, Email:mayan0825@sina.com; 高微微,Email:gwwjys@sina.com
基金资助:
“十三五”国家科技重大专项(2018ZX10722302-003-001)

Effect of a new treatment regimen on patients with initially retreated drug-sensitive pulmonary tuberculosis

Ge Qiping¹, Zhang Lijie², Huang Xuerui¹, Jiang Guanglu³, Han Xiqin⁴, Wang Jingping⁵, Du Jian²(), Ma Yan⁶(), Gao Weiwei²()

¹The 2nd Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
²Clinical Center on Tuberculosis, Beijing Chest Hospital, Capital Medical University/Clinical Center on Tuberculosis, China CDC, Beijing 101149, China
³National Tuberculosis Clinical Laboratory/Beijng Key Laboratory for Drug Resistant Tuberculosis/Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
⁴The 3rd Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
⁵Outpatient Department, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
⁶Department of Infectious Diseases Prevention and Treatment, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medicine Sciences, Beijing 100700, China

Received:2023-06-04 Online:2023-11-10 Published:2023-11-03
Contact: Du Jian, Email: jdu-sdu@163.com; Ma Yan, Email: mayan0825@sina.com; Gao Weiwei, Email: gwwjys@sina.com
Supported by:
Major National Science and Technology Projects in the 13th Five-Year Plan(2018ZX10722302-003-001)

摘要/Abstract

摘要：

目的: 分析复治肺结核治疗新方案(简称“新方案”)与复治标准方案(简称“标准化方案”)治疗首次复治敏感肺结核的有效性及安全性。方法: 采用多中心前瞻性队列研究方法,选取2019年1月至2021年12月期间在中国14个省及3个直辖市中的24家结核病定点医疗机构住院确诊的592例首次复治肺结核患者(包括敏感、单耐药、多耐药及部分菌阴复治肺结核),将患者随机纳入新方案组[4H-L₂-E-Z-Lfx/4H-L₂-E;H:异烟肼(体质量<50kg,0.3g/d;体质量≥50kg,0.4~0.5g/d),L:利福喷丁(0.6g/次,2次/周),E:乙胺丁醇(体质量<50kg,0.75g/d;体质量≥50kg,0.75~1.0g/d),Z:吡嗪酰胺(1.5g/d),Lfx:左氧氟沙星(0.5~0.6g/d)]和标准化方案组(3H-R-E-Z/6H-R-E,常规剂量;R:利福平)。本研究参照纳排标准选取其中首次复治敏感肺结核患者(均为涂阳培阳)为研究对象,比较新方案组患者和标准化方案组的治疗成功率、失败率、不良反应发生率等,以评估新方案在复治敏感肺结核患者中的有效性及安全性。结果: 共纳入首次复治敏感肺结核患者238例,其中新方案组172例(72.3%),标准化方案组66例(27.7%)。新方案组治疗成功率[77.3%(133/172)]高于标准化方案组[62.1%(41/66)],治疗失败率[4.7%(8/172)]低于标准化方案组[27.3%(18/66)],差异均有统计学意义(χ²=5.609,P=0.018;χ²=25.083,P=0.000),但两组患者不良反应发生率[4.7%(8/172)和3.0%(2/66)]差异无统计学意义(Fisher精确概率法,P=0.731)。结论: 新方案可提高首次复治敏感肺结核的治疗成功率及降低治疗失败率,总体治疗效果及安全性均较好。

关键词: 结核,肺, 再治疗, 临床方案, 方案评价, 治疗结果

Abstract:

Objective: To evaluate the efficacy and safety of a new treatment regimen against a standardized regimen on patients with retreated drug-susceptible pulmonary tuberculosis (PTB). Methods: This multi-centered study adopted a prospective study design, 592 patients with initially retreated PTB (including drug-susceptible, mono-drug resistance, poly-drug resistance and a few cases of smear negative retreated PTB) whom had been randomized into the new regimen arm (4H-L₂-E-Z-Lfx/4H-L₂-E; H: isoniazid, L: rifapentine, E: ethambutol, Z: pyrazinamide, Lfx: levofloxacin; body mass <50 kg, H for 0.3 g/d, E for 0.75 g/d; body mass ≥50 kg, H for 0.4-0.5 g/d, E for 0.75-1.0 g/d; regardless of body weight, L was 0.6 g, twice a week; Z: 1.5 g/d, Lfx: 0.5-0.6 g/d), and the standardized regimen arm (3H-R-E-Z/6H-R-E using conventional doses; R: rifampicin), diagnosed and hospitalized in between Jan 2019 and Dec 2021 by 24 PTB designated hospitals across 14 provinces and 3 municipalities in China were screened at baseline. According to inclusion and exclusion criteria, only those with initially retreated drug-susceptible PTB were recruited as study subjects. The rates of treatment success, treatment failure as well as incidence of adverse events were compared, safety and efficacy of the new regimen derived. Results: The final analysis included 238 cases, of which 172 cases (72.3%) were randomized into the new regimen arm, 66 cases (27.7%) into the standardized regimen arm. The success rate of the new regimen arm was higher than that of the standardized regimen arm (77.3% (133/172) vs. 62.1% (41/66); χ²=5.609, P=0.018), and the failure rate was lower than that of the standard regimen arm (4.7% (8/172) vs. 27.3% (18/66); χ²=25.083, P=0.000). There was no significant difference in the incidence of adverse reactions between the two arms (4.7% (8/172) vs. 3.0% (2/66); Fisher test, P=0.731). Conclusion: Compare to the standardized regimen, the new retreatment regimen had improved the treatment success rate and lowered the rate of treatment failure among patients with retreated drug-sensitive PTB, demonstrated good overall safety and efficacy profile.

Key words: Tuberculosis, pulmonary, Retreatment, Clinical protocols, Program evaluation, Treatment outcome

中图分类号:

R52
R453

戈启萍, 张立杰, 黄学锐, 姜广路, 韩喜琴, 王敬萍, 杜建, 马艳, 高微微. 首次复治敏感肺结核治疗新方案疗效的验证性研究[J]. 中国防痨杂志, 2023, 45(11): 1078-1083. doi: 10.19982/j.issn.1000-6621.20230192

Ge Qiping, Zhang Lijie, Huang Xuerui, Jiang Guanglu, Han Xiqin, Wang Jingping, Du Jian, Ma Yan, Gao Weiwei. Effect of a new treatment regimen on patients with initially retreated drug-sensitive pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2023, 45(11): 1078-1083. doi: 10.19982/j.issn.1000-6621.20230192

图/表 2

参考文献 20

[1]	Jones-López EC, Ayakaka I, Levin J, et al. Effectiveness of the standard WHO recommended retreatment regimen (category Ⅱ) for tuberculosis in Kampala, Uganda: a prospective cohort study. PLoS Med, 2011, 8(3):e1000427. doi:10.1371/journal.pmed.1000427.
[2]	World Health Organization. Treatment of tuberculosis.3rd ed. Geneva: World Health Organization, 2003.
[3]	World Health Organization. Global tuberculosis report 2019. Geneva: World Health Organization, 2019.
[4]	World Health Organization. Global tuberculosis report 2020. Geneva: World Health Organization, 2020.
[5]	马艳, 杜建, 高微微, 等. 377例复治肺结核患者耐药的危险因素研究. 中国预防医学杂志, 2018, 19(9): 641-646. doi:10.16506/j.1009-6639.2018.09.001.
[6]	舒薇, 戈启萍, 黄学锐, 等. 复治肺结核耐异烟肼患者和耐利福平患者治疗效果的分析. 中国防痨杂志, 2021, 43(4):322-327. doi:10.3969/j.issn.1000-6621.2021.04.005.
[7]	马艳, 高微微. 今非昔比:重视复治肺结核的合理施治. 中国防痨杂志, 2021, 43(4): 313-317. doi:10.3969/j.issn.1000-6621.2021.04.003.
[8]	戈启萍, 杜建, 舒薇, 等. 优化方案治疗复治药物敏感肺结核的疗效评价. 中国防痨杂志, 2021, 43(4):328-334. doi:10.3969/j.issn.1000-6621.2021.04.006.
[9]	张力, 邵伟杰, 方晴, 等. 提高剂量和延长强化期在菌阳复治肺结核患者中的疗效评价. 中国现代应用药学, 2018, 35(10):1521-1525. doi:10.13748/j.cnki.issn1007-7693.2018.10.020.
[10]	朱莉贞, 高孟秋, 陈巍, 等. 复治肺结核化疗新方案与原复治方案的临床对照研究. 中国防痨杂志, 2012, 34(5):304-309.
[11]	杜建, 刘宇红, 李亮, 等. 复治肺结核患者采用不同化疗方案的效果评价. 中国防痨杂志, 2016, 38(10):847-854. doi:10.3969/j.issn.1000-6621.2016.10.013.
[12]	中华人民共和国卫生部疾病预防控制局, 中华人民共和国卫生部医政司, 中国疾病预防控制中心. 中国结核病防治规划实施工作指南(2008年版). 北京: 中国协和医科大学出版社, 2009.
[13]	马艳, 沈鑫, 高微微. 往昔今昔:再谈复治肺结核治疗. 中国防痨杂志, 2021, 43(4):310-312. doi:10.3969/j.issn.1000-6621.2021.04.002.
[14]	张立杰, 韩喜琴, 王敬萍, 等. 痰菌量与复治菌阳肺结核治疗失败和复发的关系. 中国防痨杂志, 2021, 43(4):335-340. doi:10.3969/j.issn.1000-6621.2021.04.007.
[15]	Sekaggya-Wiltshire C, von Braun A, Lamorde M, et al. Delayed sputum culture conversion in tuberculosis-human immunodeficiency virus-coinfected patients with low isoniazid and rifampicin concentrations. Clin Infect Dis, 2018, 67(5):708-716. doi:10.1093/cid/ciy179. pmid: 29514175
[16]	郭少晨, 朱慧, 郭超, 等. 909例结核病患者一线抗结核药物血药浓度监测结果分析. 中国防痨杂志, 2018, 40(7):744-749. doi:10.3969/j.issn.1000-6621.2018.07.014.
[17]	Mei Z, Sun Z, Bai D, et al. Discrepancies in Drug Susceptibility Test for Tuberculosis Patients Resulted from the Mixed Infection and the Testing System. Biomed Res Int, 2015, 2015:651980. doi:10.1155/2015/651980.
[18]	Saha R. Predictors of Treatment Outcome for Retreatment Pulmonary Tuberculosis Cases among Tribal People of an Eastern India District: A Prospective Cohort Study. Tuberc Res Treat, 2016, 2016:8608602. doi:10.1155/2016/8608602.
[19]	Gao XF, Li J, Yang ZW, et al. Rifapentine vs. rifampicin for the treatment of pulmonary tuberculosis: a systematic review. Int J Tuberc Lung Dis, 2009, 13(7):810-819. pmid: 19555529
[20]	刘宇红, 杜建, 高微微, 等. 含链霉素或左氧氟沙星方案治疗复治肺结核患者的近期疗效及安全性. 中国防痨杂志, 2015, 37(5):487-493. doi:10.3969/j.issn.1000-6621.2015.05.005.

特征	新方案组(172例)		标准化方案组(66例)		χ²值	P值
特征	例数	构成比(%)	例数	构成比(%)	χ²值	P值
性别					1.037	0.308
男性	133	77.3	55	83.3
女性	39	22.7	11	16.7
年龄组(岁)					1.269	0.530
18~39	73	42.4	25	37.9
40~59	75	43.6	28	42.4
60~65	24	14.0	13	19.7
体质量指数					2.935	0.087
≤18.5	50	29.1	12	18.2
>18.5	122	70.9	54	81.8
治疗类型					3.355	0.187
初治失败	21	12.2	3	4.5
复发	83	48.3	37	56.1
其他	68	39.5	26	39.4
合并糖尿病	24	14.0	11	16.7	0.280	0.597
合并空洞	11	6.4	7	10.6	1.210	0.271

组别	例数	治疗成功			失访	失败	死亡
组别	例数	治愈	完成治疗	合计	失访	失败	死亡
新方案组	172	49(28.5)	84(48.8)	133(77.3)	30(17.4)	8(4.7)	1(0.6)
标准化方案组	66	34(51.5)	7(10.6)	41(62.1)	7(10.6)	18(27.3)	0(0.0)
χ²值		11.135	35.631	5.609	1.698	25.083	-
P值		0.001	0.000	0.018	0.193	0.000	0.723

首次复治敏感肺结核治疗新方案疗效的验证性研究

Effect of a new treatment regimen on patients with initially retreated drug-sensitive pulmonary tuberculosis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 2

参考文献 20

相关文章 15

编辑推荐

Metrics

本文评价

友情链接

[1]	李玉红, 梅金周, 苏伟, 阮云洲, 刘玉舒, 赵雁林, 刘小秋. 2015—2021年全国65岁及以上老年利福平耐药肺结核患者治疗转归及影响因素分析[J]. 中国防痨杂志, 2025, 47(4): 408-415.
[2]	吴璇, 张艳秋, 徐吉英, 孟丹, 孙定勇. 2019—2023年河南省肺结核合并糖尿病患者治疗转归影响因素分析[J]. 中国防痨杂志, 2025, 47(4): 425-431.
[3]	安源, 白云龙, 赵庆龙, 马建军, 姜雪, 潘艳, 高迎, 高智慧. 2018—2022年吉林省肺结核合并糖尿病患者治疗转归情况及影响因素分析[J]. 中国防痨杂志, 2025, 47(4): 432-438.
[4]	杨海霞, 张小燕, 黄毅, 黎秋. 活动性肺结核合并胸部肿瘤调强放射治疗的安全性及疗效分析[J]. 中国防痨杂志, 2025, 47(3): 312-321.
[5]	吴倩, 王伟, 张钰, 陈松华, 陈彬. 浙江省无结核社区评价指标体系构建[J]. 中国防痨杂志, 2025, 47(3): 331-337.
[6]	王大福, 马晓雪, 王芸, 李福栋, 饶文, 龚婷婷, 李世军, 李进岚. 2016—2023年贵州省合并糖尿病的肺结核患者就诊延迟及不良结局危险因素分析[J]. 中国防痨杂志, 2025, 47(2): 201-209.
[7]	李福栋, 马晓雪, 周建, 王大福, 张玥颖, 龚婷婷, 饶文, 洪峰, 李世军, 李进岚. 2018—2023年贵州省利福平敏感MTB/HIV双重感染患者流行特征及治疗转归分析[J]. 中国防痨杂志, 2025, 47(1): 36-43.
[8]	石宜林, 顾岩. 糖皮质激素联合抗结核药物治疗对结核性浆膜炎有效性、不良反应及病死率的Meta分析[J]. 中国防痨杂志, 2025, 47(1): 77-86.
[9]	范俊, 王恒, 兰汀隆, 董伟杰, 唐恺, 李元, 严广璇, 徐尚胜, 康志刚, 秦世炳. 12例非结核分枝杆菌性脊柱炎手术治疗患者临床特征及治疗转归[J]. 中国防痨杂志, 2025, 47(1): 87-95.
[10]	尹家秀. 伊沙佐米+来那度胺及地塞米松治疗复发难治性多发性骨髓瘤并发骨结核的疗效与安全性分析[J]. 中国防痨杂志, 2024, 46(S2): 118-119.
[11]	陆兵. 桉柠蒎对治疗老年肺炎的疗效观察[J]. 中国防痨杂志, 2024, 46(S2): 132-134.
[12]	李温鸿, 彭迎春, 潘梦艳. 中药灌肠联合改良芒硝袋外敷治疗急性水肿型胰腺炎并发肺损伤的临床研究[J]. 中国防痨杂志, 2024, 46(S2): 148-151.
[13]	黄易琳. 甲磺酸奥希替尼片治疗非小细胞肺癌的临床效果[J]. 中国防痨杂志, 2024, 46(S2): 152-154.
[14]	李佳霓. 桉柠蒎肠溶软胶囊治疗慢性支气管炎急性发作的临床疗效[J]. 中国防痨杂志, 2024, 46(S2): 155-157.
[15]	赵飞宇. 黄芪百合桔梗汤治疗肺结节术后咳嗽的效果分析[J]. 中国防痨杂志, 2024, 46(S2): 178-180.