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中国防痨杂志 ›› 2022, Vol. 44 ›› Issue (3): 239-245.doi: 10.19982/j.issn.1000-6621.20210702

• 论著 • 上一篇    下一篇

含贝达喹啉方案治疗耐药肺结核的不良反应分析

张玉霞, 熊瑜(), 常婷婷, 刘凤霞   

  1. 山东省公共卫生临床中心结核七病区,济南 250100
  • 收稿日期:2021-12-13 出版日期:2022-03-10 发布日期:2022-03-08
  • 通信作者: 熊瑜 E-mail:yiyiruguol@163.com

Analysis of adverse reactions of bedaquiline containing regimen in the treatment of drug-resistant pulmonary tuberculosis

ZHANG Yu-xia, XIONG Yu(), CHANG Ting-ting, LIU Feng-xia   

  1. Tuberculosis VII Ward, Shandong Public Health Clinical Center, Ji’nan 250100, China
  • Received:2021-12-13 Online:2022-03-10 Published:2022-03-08
  • Contact: XIONG Yu E-mail:yiyiruguol@163.com

摘要:

目的: 分析贝达喹啉联合常规抗结核药物治疗耐药肺结核过程中产生的不良反应,为贝达喹啉的安全使用与监测提供依据。方法: 采用回顾性研究的方法,搜集2018年11月至2020年12月于山东省公共卫生临床中心耐药结核病房完成了24周治疗及随访的127例耐多药肺结核、准广泛耐药肺结核、广泛耐药肺结核及利福平耐药肺结核患者作为研究对象,其中,使用含贝达喹啉方案治疗的66例患者作为观察组,使用不含贝达喹啉治疗方案的61例患者作为对照组。收集研究对象的临床资料,包括年龄、性别、耐药诊断类型、是否合并糖尿病、是否合用其他导致QTc间期延长的药物等。监测两组研究对象在治疗过程中药物不良反应的发生情况,分析观察组患者发生QTc间期延长(>450ms)的影响因素。结果: 观察组QTc间期延长发生率为48.5%(32/66),明显高于对照组的26.2%(16/61),差异有统计学意义(χ2=6.678,P=0.001);观察组与对照组发生QTc间期>500ms者分别有3例(4.5%)和1例(1.6%),差异无统计学意义(Fisher精确概率法,P=0.143)。两组其他药物不良反应发生情况未见差异。观察组QTc间期随着含贝达喹啉治疗方案使用时间增加逐渐增大,第4周末QTc间期为(435.1±28.8)ms,明显高于基线期QTc间期[(419.0±23.2)ms],差异有统计学意义(t=3.477,P=0.001);在第12周末达峰值[(439.5±30.7)ms]。多因素分析显示,年龄≥45岁的患者使用含贝达喹啉方案治疗时出现QTc间期延长的风险是年龄18~45岁者的9.027倍(95%CI:1.033~78.859);合并使用其他可导致QTc间期延长的药物亦是导致患者发生QTc间期延长的独立危险因素[OR(95%CI)=9.033(1.042~78.326)]。结论: 耐药肺结核患者应用含贝达喹啉方案治疗后QTc间期延长的发生率增高,但未见严重的心脏不良事件;其他系统不良事件发生率未见增加。高龄患者是QTc间期延长发生的高危人群。

关键词: 结核,肺, 结核,抗多种药物性, 药物毒性, 贝达喹啉

Abstract:

Objective: To analyze the adverse reactions of bedaquiline combined with conventional anti-tuberculosis drugs in the treatment of drug-resistant pulmonary tuberculosis, so as to provide basis for the safe use and monitoring of bedaquiline. Methods: A retrospective study was conducted in 127 patients with multidrug-resistant tuberculosis, pre-extensive drug-resistant pulmonary tuberculosis, extensively drug-resistant pulmonary tuberculosis and rifampicin-resistant pulmonary tuberculosis from the Drug-Resistant Tuberculosis Ward of Shandong Public Health Clinical Center. All of them completed 24-week treatment and follow-up from November 2018 to December 2020. And 66 patients treated with bedaquiline containing regimen were considered as the observation group, the other 61 patients treated without bedaquiline containing regimen were considered as the control group. Clinical data including age, gender, drug resistance type, whether or not complicated with diabetes mellitus, whether or not take other drugs that led to prolonged QTc interval, etc., were collected. The occurrence of adverse drug reactions in the treatment of the two groups was monitored, and the influencing factors of QTc interval prolongation (>450 ms) in the observation group were analyzed. Results: The incidence of QTc interval prolongation in the observation group was 48.5% (32/66), which was significantly higher than that in the control group (26.2% (16/61)) (χ2=6.678, P=0.001). There were 3 cases (4.5%) and 1 case (1.6%) with QTc interval >500 ms in the observation group and the control group, respectively. The difference was not statistically significant (Fisher exact probability method, P=0.143). There was no difference in the occurrence of other adverse drug reactions between the two groups. The QTc interval in the observation group gradually increased with the use time of the treatment regimen containing bedaquiline. At the end of the 4th week, the QTc interval was (435.1±28.8) ms, which was significantly higher than that in the baseline period ((419.0±23.2) ms) (t=3.477, P=0.001), and the peak appeared at the end of the 12th week ((439.5±30.7) ms). Multivariate analysis showed that, if treated with bedaquiline containing regimen, the risk of QTc interval prolongation in patients aged ≥45 years was 9.027 times (95%CI: 1.033-78.859) of that in patients aged 18-45 years; combined use of other drugs that can lead to QTc interval prolongation was also an independent risk factor for QTc interval prolongation (OR (95%CI)=9.033 (1.042-78.326)). Conclusion: The incidence of QTc interval prolongation increased in patients with drug-resistant pulmonary tuberculosis after treatment with bedaquiline containing regimen, but there was no serious adverse cardiac events. The incidence of adverse events in other systems did not increase. Elderly patients were at high risk of QTc interval prolongation.

Key words: Tuberculosis,pulmonary, Tuberculosis,multidrug-resistant, Drug toxicity, Bedaquiline

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