含新药口服短程方案治疗耐多药/利福平耐药结核病三例并文献复习

An all-oral shortened regimen containing new drugs to treat MDR/rifampicin-resistant tuberculosis:three case reports and literature review

目的:探讨含新药口服短程方案治疗耐多药/利福平耐药结核病的疗效和安全性,为临床医师应用该方案治疗提供更多的依据。方法:回顾性分析2023年12月北京胸科医院收治的3例应用含新药口服短程方案(贝达喹啉、康替唑胺、德拉马尼)治疗的耐多药/利福平耐药结核病患者的相关临床资料,通过查阅中国知网、万方数据库及PubMed数据库,以“耐多药结核、康替唑胺”和“耐多药结核、贝达喹啉、德拉马尼”为中文关键词,以“contezolid、multidrug-resistant tuberculosis”及“multidrug-resistant tuberculosis、bedaquiline、delamanid”为英文关键词进行文献检索,共搜索到国内外相关文献11篇,本研究主要选取含新药康替唑胺、德拉马尼、贝达喹啉短程治疗的文献8篇,结合本组3例患者的病历资料进行有效性和安全性分析。结果:有效性分析显示,含康替唑胺方案治疗的患者中,84%的患者痰培养和(或)涂片结核分枝杆菌阴性,且持续为阴性。治疗期间胸部CT检查显示病灶缩小,停药后胸部CT检查提示病灶稳定。含贝达喹啉、德拉马尼方案治疗的患者中,91%的患者获得了良好的结果。在治疗第8周,痰结核分枝杆菌培养阴转率为95%,第24周时为95%。贝达喹啉联合德拉马尼组的痰涂片和培养阴转中位时间均快于贝达喹啉组。安全性分析显示,含康替唑胺方案治疗的患者未发生骨髓抑制、周围神经病变和视神经病变等在内的利奈唑胺常见不良反应。而在含贝达喹啉和德拉马尼治疗的患者中,QTcF间期相比基线延长了20.7ms(平均16.1~25.3ms),2例患者出现QT间期延长大于500ms,4例患者发生6次QTcF间期延长超过基线值60ms,在治疗期间没有发生3级或4级不良QTc延长事件,未发生心律失常,没有一例永久停药,也没有发生死亡。贝达喹啉联合德拉马尼组QTc间期延长少于贝达喹啉组。在治疗过程中,52%的患者出现骨髓抑制,42%的患者出现周围神经病变。在48周随访时,大多数不良事件得到解决。结论:含新药贝达喹啉、德拉马尼、康替唑胺的全口服方案在耐药结核病短程治疗中取得了较好的效果。治疗期间仅出现轻度药物不良反应,经对症治疗后均缓解,未出现严重药物不良反应。

Objective:To evaluate the efficacy and safety of a novel all-oral short-course regimen for the treatment of multidrug-resistant(MDR)and rifampicin-resistant(RR)tuberculosis(TB).Methods:A retrospective analysis was conducted on the clinical data of three MDR/RR-TB patients who received a short-course oral regimen containing new drugs(bedaquiline,contezolid and delamanid)at Beijing Chest Hospital in December 2023.Using the keywords“multidrug-resistant tuberculosis,contezolid”and“multidrug-resistant tuberculosis,bedaquiline,delamanid”relevant studies were retrieved from CNKI,Wanfang,and PubMed databases.A total of 11 studies were identified,8 of which included new drugs such as contezolid,delamanid and bedaquiline.The efficacy and safety of these regimens were analyzed in combination with the clinical data of the three reported cases.Results:Efficacy analysis revealed that 84%of patients receiving contezolid-based regimens achieved negative sputum cultures and(or)smears for Mycobacterium tuberculosis.Chest CT scans indicated lesion improvement,with stability maintained after treatment cessation.Among patients treated with bedaquiline and delamanid-based regimens,91%showed favorable outcomes.The sputum culture conversion rate for Mycobacterium tuberculosis was 95%at week 8 and remained at 95%at week 24 of treatment.Additionally,the median time to sputum culture conversion in the bedaquiline and delamanid group was shorter compared to that of the bedaquiline-only group.Safety analysis revealed that no cases of myelosuppression,peripheral neuropathy,or optic neuropathy were observed in patients receiving contezolid-based regimens.In the bedaquiline and delamanid group,the QTcF interval increased by an average of 20.7 ms from baseline(mean range:16.1 ms to 25.3 ms),with 2 patients experiencing a QT prolongation of>500 ms.Additionally,4 patients experienced 6 instances of QTcF prolongation exceeding baseline by 60 ms.No grade 3 or 4 QTc prolongation events,arrhythmias,permanent treatment discontinuations,or deaths were reported.The extent of QTc prolongation was lower in the bedaquiline and delamanid group compared to the bedaquiline-only group.During treatment,52%of patients developed myelosuppression,and 42%experienced peripheral neuropathy.By 48 weeks of follow-up,most adverse events had resolved.Conclusion:The all-oral short-course regimen containing new drugs(bedaquiline,delamanid,and contezolid)demonstrated promising efficacy in patients with multidrug-resistant or rifampicin-resistant tuberculosis.No serious drug-related adverse events were observed throughout the treatment course.