含贝达喹啉方案治疗耐多药/广泛耐药结核病的24周单臂临床疗效观察

目的 评价含贝达喹啉方案治疗耐多药/广泛耐药结核病的疗效，并探索其发生的不良反应，为临床安全合理用药提供参考。方法 回顾性分析2019年10月至2021年10月昆明市第三人民医院收治的使用含贝达喹啉方案治疗的62例耐多药/广泛耐药结核病患者的临床资料，对含贝达喹啉方案的有效性和安全性进行评价；统计背景药品组成种类、痰菌阴转例数与天数、病灶吸收、空洞闭合及不良反应事件分布，并分析其相关性；记录服药前后QTcF值（按心率校正，采用Fridericia公式计算的QT间期值），对比分析各监测点与基线的变化。结果 62例患者24周随访全部到位，无死亡、失访或退组病例；治疗24周末62例患者痰涂片阴转率为93.5%(58/62)，痰培养阴转率为85.4%(53/62)，病灶吸收率为87.1%(54/62)，并发空洞的39例患者空洞闭合率为92.3%(36/39)。不良事件共计217次，203次（93.5%）为轻中度（Ⅰ～Ⅱ级）不良事件，14次（6.5%）为严重（Ⅲ～Ⅴ级）不良事件；治疗期间共停药22次，与贝达喹啉相关的不良事件停药11次，主要表现为QTc间期延长9次（41.0%），肝脏毒性2次（9...

Early Effectiveness of Bedaquiline Containing Regimen in Treatment of Multidrug-resistant and Extensively Drug-resistant Pulmonary Tuberculosis: An One-arm Observational Study of 24 Weeks

  Objective   To evaluate the efficacy of a bedaquiline-containing regimen in the treatment of multidrug-resistant/extensively drug-resistant tuberculosis, and to explore the adverse reactions, so as to provide a reference for safe and rational drug use in clinical practice.   Methods   The clinical data of 62 patients with multi-drug resistant/extensively drug-resistant tuberculosis treated with a bedaquiline-containing regimen from October 2019 to October 2021 in the Third People’s Hospital of Kunming were retrospectively analyzed to evaluate the efficacy and safety of bedaquiline-containing regimen. Background Drug composition, number and days of sputum negative conversion, lesion absorption, cavity closure, and distribution of adverse events were counted, and their correlation was analyzed. QTcF values （corrected for heart rate, QT interval values calculated using the Fridericia formula） were recorded before and after medication, and changes from baseline at each monitoring point were compared and analyzed.   Results  All 62 patients were followed up for 24 weeks, and there were no deaths, lost to follow-up or withdrawal cases; At the end of 24 weeks of treatment, the sputum smear-negative conversion rate was 93.5% （58/62）, the sputum culture negative conversion rate was 85.4% （53/62）, the lesion absorption rate was 87.1% （54/62）, and the cavity closure rate was 92.3% （36/39） in 39 patients with cavities. There were a total of 217 adverse events, 203 （93.5%） were mild to moderate （grade 1 to 2） adverse events and 14 （6.5%） were serious （grade 3 to 5） adverse events. A total of 22 discontinuations were performed during treatment. Bedaquiline-related adverse events were 11 discontinuations, mainly manifested as QTc prolongation in 9 （41.0%） and hepatotoxicity in 2 （9.1%）. Statistical calculation results showed that abnormal liver function was negatively correlated with sputum negative conversion time （z = -0.293, P < 0.01）; QTc interval prolongation was negatively correlated with sputum negative conversion time （z = -0.544, P < 0.01）. Sixty-two patients were compared between the mean QTcF value at each monitoring site and the baseline QTcF value, and the QTcF value gradually increased with the extension of the course of treatment, and the differences at weeks 4, 8, 12, 16, and 24 were statistically significant.   Conclusions  Bedaquiline-containing regimens achieve a high rate of sputum negative conversion at 24 weeks in the treatment of multidrug-resistant/extensively drug-resistant tuberculosis and can promote the absorption of imaging lesions in patients. Although the incidence of adverse drug reactions is high, they are generally controllable and tolerable to most patients. Special attention should be paid to QTc prolongation and liver injury during medication.