摘要
目的分析16例应用含贝达喹啉方案治疗的耐多药/广泛耐药结核病(MDR-TB/XDR-TB)患者的近期疗效及安全性。方法选取2018年9月至2020年1月福建省福州肺科医院使用含贝达喹啉方案治疗且符合MDR-TB纳入标准的患者16例作为研究对象,其中MDR-TB患者4例,XDR-TB患者6例,pre-XDR-TB患者6例,分析24周痰培养阴转情况和监测入组前1周内、2周、4周、8周、12周、16周、20周、24周心电图QTc间期的变化及入组前1周内、12周、24周胸部病灶变化,记录药物不良反应及处理情况。结果16例患者均完成24周强化治疗,痰菌中位阴转时间为8(4,12)周,阴转时间2例为4周、10例为8周、3例为12周,1例患者培养持续阳性;胸部CT扫描肺部病灶显示7例显著吸收,7例部分吸收,2例不变。不良反应以例次计算,主要集中在QTc间期延长(25.8%,42/163)、可以耐受的胃肠道反应(22.1%,36/163)、肝功能异常(3.7%,6/163)、高尿酸血症(36.8%,60/163)、白细胞减少(4.3%,7/163)、乏力、关节肌肉酸痛(3.1%,5/163)、呼吸衰竭(0.6%,1/163)、皮肤红染(3.7%,6/163)。16例患者的基线心电图QTc间期值中位数为412.50(398.25,420.75)ms;各监测时间[治疗2周为414.00(405.00,426.75)ms,治疗4周为419.50(402.00,434.50)ms,治疗8周为410.50(398.25,421.25)ms,治疗12周为421.50(409.50,434.75)ms,治疗16周为424.50(413.75,432.25)ms,治疗20周为421.50(409.50,434.75)ms,治疗24周为424.00(414.00,435.25)ms]的QTc间期值与基线QTc间期值对比,治疗开始后12周、16周、20周、24周差异有统计学意义(Z=-2.198,P=0.028;Z=-2.096,P=0.036;Z=-1.965,P=0.049;Z=-2.406,P=0.016)。16例患者均未出现QTc间期>500ms。结论含贝达喹啉方案治疗MDR-TB患者获得了较好的临床疗效,且临床安全性较高,丰富了MDR-TB患者的临床药物选择。
Objective To analyze the short-term effectiveness and safety of bedaquiline-containing regimen in16 patients with multidrug-resistant tuberculosis(MDR-TB)or extensively drug-resistant tuberculosis(XDR-TB).Methods From September 2018 to January 2020,16 patients treated with bedaquiline regimen and met the inclusion criteria in Fuzhou Pulmonary Hospital were selected,including 4 MDR-TB patients,6 XDR-TB patients,and 6 pre-XDR-TB patients.The conversion of sputum culture for Mycobacterium tuberculosis at 24 weeks was analyzed.Changes of electro-cardiogram QTcF at 1,2,4,8,12,16,20,24 weeks before enrollment and changes of chest lesions at 12 and 24 weeks after treatment were monitored,and adverse drug reactions and treatment for them were recorded.Results All of the 16 patients completed 24 weeks of intensive therapy,and the median time of sputum culture conversion was 8(IQR:4,12)weeks.The time of conversion was 4 weeks in 2 patients,8 weeks in 10 patients,and 12 weeks in 3 patients,1 patient was continuously positive in culture.Chest CT scan of lung lesions showed significant absorption in 7 cases,partial absorption in 7 cases,and no change in 2 cases.Adverse reactions mainly were prolonged QTcF(25.8%,42/163),tolerable gastrointestinal reactions(22.1%,36/163),abnormal liver function(3.7%,6/163),hyperuricemia(36.8%,60/163),and leukopenia(4.3%,7/163),fatigue,joint muscle soreness(3.1%.5/163),respiratory failure(0.6%,1/163),and skin redness(3.7%,6/163).The median ECG QTcF value at baseline time for those 16 patients was 412.50(IQR:398.25,420.75)ms,while it changed to 414.00(405.00,426.75)ms at 2 weeks,419.50(402.00,434.50)ms at4 weeks,410.50(398.25,421.25)ms at 8 weeks,421.50(409.50,434.75)ms at 12 weeks,and 424.50(413.75,432.25)ms at 16 weeks,421.50(409.50,434.75)ms at 20 weeks and 424.00(414.00,435.25)ms at24 weeks.There were statistically significant differences at 12,16,20 and 24 weeks comparing with the baseline(Z=-2.198,P=0.028;Z=-2.096,P=0.036;Z=-1.965,P=0.049;Z=-2.406,P=0.016).None of the16 patients had QTcF>500 ms.Conclusion The treatment regimen containing bedaquiline showed good clinical effectiveness and high safety in the treatment of MDR-TB patients,which can enrich the clinical drug selection for treating MDR-TB.
作者
吴国兰
高静韬
陈晓红
陈力舟
翁丽珍
郭志平
陈秀平
林剑东
陈素霞
高孟秋
刘宇红
WU Guo-lan;GAO Jing-tao;CHEN Xiao-hong;CHEN Li-zhou;WENG Li-zhen;GUO Zhi-ping;CHEN Xiu-ping;LIN Jian-dong;CHEN Su-xia;GAO Meng-qiu;LIU Yu-hong(Fuzhou Pulmonary Hospital of Fujian,Fuzhou 350008,China;不详)
出处
《中国防痨杂志》
CAS
CSCD
2021年第9期899-904,共6页
Chinese Journal of Antituberculosis
基金
福建省福州市临床医学中心项目(2018080305)。
关键词
泛耐药结核病
贝达喹啉
药物评价
观察性研究
Extensively drug-resistant tuberculosis
Bedaquiline
Drug evaluation
Observational study
