205例含贝达喹啉方案治疗耐多药肺结核的24周有效性与安全性分析

Efficacy and safety analysis of a 24-week bedaquiline-containing regimen in 205 cases of multidrug-resistant pulmonary tuberculosis

摘要:

目的 评估贝达喹啉联合新型或常规药物方案治疗耐多药肺结核患者24周的临床有效性与安全性。方法 纳入2019年3月至2024年6月于广州市胸科医院接受贝达喹啉方案治疗的205例耐多药肺结核患者，收集人口学资料、治疗效果以及服药前后多时间点心电图经Fridericia公式校正的QT间期（QTcF）值变化情况，观察治疗期间不良反应的发生。结果 （1）痰菌阴转：治疗2个月末痰菌阴转率为89.76%，6个月末痰菌阴转率为98.05%。（2）安全性：205例中有4例因不良反应中途停用贝达喹啉，常见不良反应包括胃肠道症状、头晕、视物模糊及肝功能异常等，大多可耐受或经对症处理好转。（3） QTcF变化：服药前QTcF中位数值为392.92 ms，治疗期间各时间点呈一过性延长趋势，于第20周达到最高（422.52 ms）后趋于平稳。Friedman检验提示各时间点间QTcF值差异有统计学意义（P＜0.001），进一步Wilcoxon检验结果显示，与服药前相比，多数时间点QTcF值升高明显，治疗后期QTcF值相对稳定。7例同时接受贝达喹啉与德拉马尼联合治疗的患者，在各观察时间点与单用贝达喹啉的患者相比，其QTcF值差异均无统计学意义（P＞0.05）。治疗期间未观察到严重不良反应。结论 贝达喹啉联合多药治疗方案可在较短时间内显著提高耐多药结核病患者的痰菌阴转率，安全性良好；一定程度上可导致QTcF延长，但在临床监测下总体风险可控。德拉马尼的联合使用对QTcF延长的影响尚需进一步扩大样本、多中心的研究加以证实。

Abstract:

Objective To assess the clinical efficacy and safety of bedaquiline combined with new or conventional drug-resistant pulmonary tuberculosis (TB) for 24 weeks.Methods A total of 205 patients with multidrug-resistant pulmonary tuberculosis who received bedaquiline-based treatment at Guangzhou Chest Hospital from March 2019 to June 2024 were included. Demographic data, treatment outcomes, and changes in the Fridericia-corrected QT interval (QTcF) values at multiple time points before and after medication were collected. Adverse reactions during the treatment period were observed.Results (1) Sputum conversion rate: At the end of the second month of treatment, the sputum conversion rate was 89.76%, and at the end of the sixth month, the sputum conversion rate was 98.05%. (2) Safety: Among the 205 cases, bedaquiline was discontinued due to adverse reactions, and the common adverse reactions included gastrointestinal symptoms, dizziness, blurred vision, and abnormal liver function, most of which were tolerated or improved by symptomatic treatment. (3) Change of QTcF: the median QTcF value before administration was 392.92 ms, which showed a transient prolongation trend at each time point during the treatment period, reaching the highest (422.52 ms) at the 20th week and then stabilizing it. The Friedman test showed that there was a statistically significant difference in QTcF value between different time points (P＜0.001). Further Wilcoxon test results showed that the QTcF value was significantly increased at most time points compared with before drug administration, and the QTcF value was relatively stable in the late treatment period. There was no significant difference in the distribution of QTcF values between the seven patients who received bedaquiline and delamanid at each observation time point compared with the patients who received bedaquiline alone (P＞0.05). No serious adverse effects were observed during the treatment period.Conclusion Bedaquiline combined with multi-drug therapy regimen can significantly increase the sputum bacterial conversion rate in patients with multidrug-resistant (MDR)-TB in a short period of time, and the safety profile is good. To a certain extent, it can lead to QTcF prolongation, but the overall risk is controllable under clinical monitoring. The effect of the combination of delamanid on QTcF prolongation needs to be confirmed in a further sample, multicenter study.