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中国防痨杂志 ›› 2021, Vol. 43 ›› Issue (9): 893-898.doi: 10.3969/j.issn.1000-6621.2021.09.007

• 论著 • 上一篇    下一篇

含贝达喹啉方案治疗耐多药肺结核的早期疗效和安全性研究

丁彩红, 熊瑜(), 王庆, 高绪胜, 郝焱   

  1. 250013 济南,山东省胸科医院结核科(丁彩红、熊瑜、王庆、高绪胜);美国石溪大学(郝焱)
  • 收稿日期:2021-07-15 出版日期:2021-09-10 发布日期:2021-09-07
  • 通信作者: 熊瑜 E-mail:yiyiruguo1@163.com
  • 基金资助:
    重大新药创制国家科技重大专项基金(2017ZX09304009);山东省医药卫生科技发展计划面上项目(2019WS523)

Study on the early efficacy and safety of the regimen containing bedaquiline in the treatment of multidrug-resistant pulmonary tuberculosis

DING Cai-hong, XIONG Yu(), WANG Qing, GAO Xu-sheng, HAO Yan   

  1. Department of Tuberculosis, Shandong Chest Hospital, Ji’nan, Shandong Province, China
  • Received:2021-07-15 Online:2021-09-10 Published:2021-09-07
  • Contact: XIONG Yu E-mail:yiyiruguo1@163.com

摘要:

目的 观察含贝达喹啉方案治疗耐多药肺结核(multidrug-resistant pulmonary tuberculosis,MDR-PTB)的早期疗效和安全性。方法 采用前瞻性研究的方法,选取2018年9月至2020年12月山东省胸科医院诊断为MDR-PTB且符合入组标准,并最终完成24周含贝达喹啉抗结核方案治疗的79例患者作为研究对象。收集研究对象基本特征资料[包括性别、年龄、居住地、体质量指数(BMI)],以及痰分枝杆菌涂片及培养结果、心电图、血常规、肝肾功能、胸部CT、药物不良反应等临床资料。监测研究对象在贝达喹啉治疗期间的痰培养阴转时间和药物不良反应发生情况,以及治疗结局,并分析影响治疗结局的因素。结果 79例研究对象在完成24周治疗后,72例(91.1%)结局良好,7例(8.9%)出现不良结局;多因素logistic回归分析显示,BMI<18.5[20.8%(5/24)]和年龄≥45岁[27.8%(5/18)]是研究对象出现不良结局的危险因素[OR(95%CI)值分别为:9.393(1.443~61.125)和7.769(1.289~46.835)]。痰培养阴转时间中位数(四分位数)为4(2,8)周,累计痰培养阴转率随治疗时间的延长而逐渐增高,第2、4、8、12、16、20、24周时的痰培养阴转率分别为30.4%(24/79)、51.9%(41/79)、70.9%(56/79)、83.5%(66/79)、87.3%(69/79)、88.6%(70/79)、91.1%(72/79)。53例患者(67.1%)出现药物不良反应,其中1例出现严重胃肠道反应,30例(38.0%)出现Q-Tc间期延长,Q-Tc间期≥500ms者15例(19.0%);Q-Tc间期随贝达喹啉使用时间的增加而呈现先上升再下降的现象,第12周为最高峰[(436.10±27.97)ms]。结论 含贝达喹啉方案治疗MDR-PTB有较好的治疗转归,早期即有较高的痰培养阴转率,营养不良和中老年患者易出现不良结局。治疗过程中应注意监测患者Q-Tc间期。

关键词: 结核,抗多种药物性, 贝达喹啉, 疗效, 安全性

Abstract:

Objective To investigate the early efficacy and safety of the regimen containing bedaquiline in the treatment of multidrug-resistant pulmonary tuberculosis (MDR-PTB). Methods According to the inclusion criteria, 79 MDR-PTB patients diagnosed in Shandong chest hospital from September 2018 to December 2020 were prospectively studied, all of them completed 24-week anti-tuberculosis treatment containing bedaquiline. Basic characteristics (gender, age, residence, body mass index (BMI)) and clinical information (mycobacterium sputum smear and culture results, electrocardiogram, blood routine, liver and kidney function, chest CT, adverse drug reactions), etc.) were collected. To monitor the time of negative conversion of sputum culture, the occurrence of adverse drug reactions, and the treatment outcome during the treatment containing bedaquiline were monitored, and the factors affecting the treatment outcome were analyzed. Results Of the 79 cases, 72 (91.1%) had good outcomes and 7 (8.9%) had adverse outcomes after completing 24-week treatment. Multivariate logistic regression analysis showed that BMI <18.5 (20.8% (5/24)) and aged ≥45 years (27.8% (5/18)) were the risk factors for adverse outcomes (OR (95%CI) were 9.393 (1.443-61.125) and 7.769 (1.289-46.835), respectively. The median (quartile) of sputum culture negative conversion time was 4 (2, 8) weeks. The cumulative sputum culture negative conversion rate gradually increased with the extension of treatment time. The sputum culture negative conversion rates at 2, 4, 8, 12, 16, 20 and 24 weeks were 30.4% (24/79), 51.9% (41/79), 70.9% (56/79), 83.5% (66/79), 87.3% (69/79), 88.6% (70/79) and 91.1% (72/79), respectively. Fifty-three patients (67.1%) had adverse drug-resistant, of which one had serious gastrointestinal reactions, 30 (38.0%) had prolonged Q-Tc interval, and Q-Tc interval ≥500 ms was found in 15 (19.0%); the Q-Tc interval increased first and then decreased with the increase in usage time of bedaquiline, and the peak was at the 12th week ((436.10±27.97) ms). Conclusion The treatment containing bedaquiline showed good outcome for MDR-PTB, with a higher rate of negative conversion of sputum culture in the early stage; adverse outcomes were more likely to happen in malnutrition, middle-aged and elderly patients. The Q-Tc interval of patients during treatment should be monitored.

Key words: Tuberculosis,multidrug resistance, Bedaquiline, Efficacy, Safety