含贝达喹啉方案治疗44例痰菌阳性耐多药/广泛耐药肺结核24周疗效分析

Analysis of efficacy in the treatment of 44 pulmonary tuberculosis patients with mycobacterium culture-positive multidrug-resistant/extensively drug-resistant with bedaquiline-containing regimen for 24 weeks

目的评估含贝达喹啉(bedaquiline,Bdq)方案治疗菌阳耐多药肺结核(MDR-PTB)/准广泛耐药肺结核(pre-XDR-PTB)/广泛耐药肺结核(XDR-PTB)的有效性和安全性,为中国耐药肺结核患者使用Bdq提供临床数据支持。方法纳入2018年3月至2020年3月就诊于南华大学附属长沙中心医院痰分枝杆菌培养阳性的MDR-PTB、pre-XDR-PTB和XDR-PTB患者44例,其中男性31例,女性13例,中位年龄38.2(26,49)岁,25例并发空洞。给予含贝达喹啉方案治疗,分析24周痰分枝杆菌培养阴转率和肺部空洞闭合率评估方案的有效性,分析不良事件(adverse event,AE)发生情况,尤其是QT间期延长的不良事件评估方案的安全性。结果 44例患者中,38例痰菌阴转成功,2例痰菌阴转失败,2例死亡,1例退组,1例失访,良好转归占比86.4%(38/44)。完成24周治疗患者第2、4、8、12、24周痰分枝杆菌培养阴转率分别为45.5%(20/44)、72.5%(29/40)、95.0%(38/40)、100.0%(40/40)和95.0%(38/40),痰菌阴转的中位时间为22 (18,59)d。并发空洞的25例患者中,23例完成24周治疗,12周和24周末空洞闭合率分别为39.1%(9/23)和82.6%(19/23)。29例患者(65.9%,29/44)累积报告了81次AE,72.8%(59/81)为1级或2级,与Bdq相关的AE主要为QT间期延长(18例,40.9%)。结论 MDR-PTB、pre-XDR-PTB和XDR-PTB患者使用含Bdq的治疗方案24周痰菌阴转率和空洞闭合率较高,安全性及耐受性良好。

Objective To evaluate the efficacy and safety of 24-week bedaquiline(Bdq)-containing regimen on multidrug-resistant pulmonary tuberculosis and extensively drug-resistant pulmonary tuberculosis(MDR/XDRPTB)patients and provide clinical evidence for further safe and effective use in more Chinese MDR/XDR-PTB patients. Methods Forty-four patients with mycobacterium culture-positive MDR-TB and XDR-TB were enrolled in Changsha Central Hospital Affiliated to University of South China from March 2018 to March 2020 and then treated with Bdq-containing regimen.Out of them,31 were males and 13 were females with a median age of 38.2(26,49)years in the whole,while 25 with pulmonary cavities.The efficacy of the regimen was evaluated by culture conversion rates and pulmonary cavity closure rate at the end of 24 weeks,and the safety was evaluated by the incidence of adverse events,especially the occurrence of QT prolongation.Results Out of 44 patients,38 achieved successful culture conversion,2 failed sputum conversion,2 died,1 dropped out,and 1 lost to follow-up,with favorable outcome at 86.4%(38/44).Forty patients completed 24 weeks of Bdq treatment,and the culture conversion rates were 45.5%(20/44),72.5%(29/40),95.0%(38/40),100.0%(40/40)and 95.0%(38/40)at the end of 2,4,8,12 and 24 weeks,respectively,with the median conversion time at 22 days(interquartile range IQR18-59).Among the 25 patients with pulmonary cavities,23 completed 24 weeks of treatment,and the rate of pulmonary cavity closure was 39.1%(9/23)and 82.6%(19/23)at the end of 12 and 24 weeks,respectively.Twenty-nine patients(65.9%,29/44)reported a total of 81 adverse events(AEs),72.8%(59/81)of which were grade 1 or 2.QT prolongation was the most common one probably associated with Bdq(40.9%,18/44).Conclusion Inclusion of Bdq in the regimen can achieve higher rates of culture conversion and cavity closure at the end of 24 weeks with acceptable safety profiles in MDR/XDR-TB patients.