含贝达喹啉的联合方案治疗耐多药结核病的疗效及安全性研究

Efficacy and safety of combination regimen containing betaquinoline in the treatment of multidrug-resistant tuberculosis

目的研究含贝达喹啉的联合抗结核方案治疗耐多药结核病的疗效及安全性。方法收集2018年3月-2019年8月成都市公共卫生临床医疗中心收治的采用含贝达喹啉的联合抗结核方案治疗的69例耐多药结核病患者作为试验组,同时将2016年6月-2017年12月接受不含贝达喹啉治疗的60例耐多药结核病患者作为对照组,比较两组的疗效及安全性。结果试验组69例,其中男44例,女25例;年龄21~63岁,平均(34.6±11.0)岁;58例(84.1%)完成24周贝达喹啉治疗,11例未完成治疗,包括死亡3例(4.3%)、失访1例(1.4%)、退出研究1例(1.4%)以及因不良事件停药6例(8.7%);54例基线痰培养抗酸杆菌阳性的患者中,49例在治疗24周内痰培养结核杆菌转为阴性(阴转率为90.7%),中位阴转时间为13.0周。对照组60例,其中男45例,女15例;年龄16~66岁,平均(35.5±13.2)岁;53例基线痰培养抗酸杆菌阳性的患者中,30例在治疗24周内痰培养结核杆菌转为阴性(阴转率为56.6%),中位阴转时间为12.0周。试验组的24周痰菌阴转率明显高于对照组(χ^(2)=16.133,P<0.001)。试验组最常见的不良反应是肝功能异常(42例,60.9%)、QTc间期延长(37例,53.6%)、电解质紊乱(20例,29.0%)及血液系统损害(20例,29.0%)。37例QTc间期延长的患者中,包括8例QTc间期≥500 ms及29例QTc间期≥450 ms且<500 ms,中位发生时间为16.0周,其中25例患者在贝达喹啉停药后4~48周发生QTc间期延长。结论含贝达喹啉的联合抗结核方案治疗耐多药结核病的痰培养阴转率高,但在治疗期间及治疗结束后需严密监测心电图,警惕贝达喹啉的潜在心脏毒副作用。

Objective To study the efficacy and safety of combined anti-tuberculosis regimen containing bedaquiline in the treatment of multidrug-resistant tuberculosis(MDR-TB).Methods A total of 69 MDR-TB patients treated by joint regimen combined bedaquiline with other anti-tuberculosis drugs between March 2018 and August 2019 in Public Health Clinical Center of Chengdu were taken as the trial group,and 60 MDR-TB patients received treatment without bedaquiline between June 2016 and December 2017 in the same hospital were taken as the control group.The efficacy and safety of the two groups were compared.Results The 69 patients in the trial group included 44 males and 25 females,aged from 21 to 63 years,with an average of(34.6±11.0)years;58 patients(84.1%)completed the 24-week treatment with bedaquiline,while 11 patients did not complete the treatment,including 3 deaths(4.3%),1 loss of followup(1.4%),1 withdrawal from the study(1.4%),and 6 discontinuation due to adverse events(8.7%).Among the 54 patients with positive results of tuberculosis on baseline sputum culture,49 transformed to negative results within 24 weeks of treatment(the negative conversion rate was 90.7%),and the median negative conversion time was 13.0 weeks.The 60 patients in the control group included 45 males and 15 females,aged from 16 to 66 years,with an average of(35.5±13.2)years.Among the 53 patients with positive results of tuberculosis on baseline sputum culture,30 transformed to negative results within 24 weeks of treatment(the negative conversion rate was 56.6%),and the median negative conversion time was 12.0 weeks.The negative conversion rate of sputum bacteria in the trial group was significantly higher than that in the control group(χ^(2)=16.133,P<0.001).The most common adverse reactions in the trial group were liver function abnormalities(42 cases,60.9%),prolonged QTc interval(37 cases,53.6%),electrolyte disturbances(20 cases,29.0%),and blood system damage(20 cases,29.0%).In the 37 patients who experienced prolonged QTc interval,there were 8 patients with QTc intervals≥500 ms and 29 patients with QTc intervals≥450 ms and<500 ms,with a median occurrence time of16.0 weeks,among whom 25 patients experienced prolonged QTc interval in 4-48 weeks after the withdrawal of bedaquiline.Conclusion The negative conversion rate of tuberculosis sputum culture of patients with MDR-TB treated by bedaquiline combined with other anti-tuberculosis drugs is high,but electrocardiogram should be closely monitored during and after the treatment in order to guard against the potential cardiac toxic effects of bedaquiline.