艰难梭菌感染的临床治疗策略及新药物研究进展

Research progress of clinical treatment strategies and new drugs for Clostridium difficile infection

艰难梭菌(Clostridium difficile)是一种革兰阳性厌氧芽孢杆菌,因导致医院内腹泻备受关注。由于C. difficile的分离培养需要在厌氧状态下实现,这给国内外研究者带来非常大的限制和挑战。目前临床治疗手段主要采取抗生素和粪便微生物群移植(fecal microbiota transplantation, FMT)。据统计艰难梭菌感染(C. difficile infection, CDI)经万古霉素治疗后复发率高达30%,死亡率达15%,是临床上亟待解决的难题。目前,许多国家在大力开发有效的新型药物来治疗CDI。本文根据目前的临床治疗现状和正在开发中的新药物进行了简要总结,更新了目前5种已有临床实验的新型抗菌药物和11种新开发的不同抗菌剂,前者包括ridinilazole、surotomycin、cadazolid、CRS3123和DS-2969b;后者包括黄芩苷、rhodomyrtone、OPS-2071、rakicidin B、依拉环素、双环胍、CM-A、月桂酸、NCK-10、Raja 42和AJ-024。针对现有临床前和临床抗菌数据,将这些潜在药物与传统抗生素进行比较,分析其所具有的药代动力学和药效特征优势,以期为CDI的新药研发提供新思路。

Clostridium difficile,a Gram-positive anaerobic bacillus,has attracted much attention for causing nosocomial diarrhea.The isolation and cultivation of C.difficile need to be achieved under anaerobic conditions,which brings great limitations and challenges to researchers.At present,the main clinical treatment methods are antibiotics and fecal microbiota transplantation(FMT).According to the survey analysis,the recurrence rate of C.difficile infection(CDI)after vancomycin treatment is as high as 30%,and the mortality rate is 15%,which is an urgent clinical problem needs to be solved.At present,many countries are vigorously developing effective new drugs to treat CDI.This article briefly summarizes the current status of clinical treatment and new drugs in development,and updates the current five new antibacterial agents that have been tested in clinical trials and 11 different newly developed antimicrobials.The former category includes ridinilazole,surotomycin,cadazolid,CRS3123,and DS-2969b.The latter includes baicalin,rhodomyrtone,OPS-2071,rakicidin B,eravacycline,bicycloguanidine,CM-A,lauric acid,NCK-10,Raja 42,and AJ-024.Based on the existing pre-clinical and clinical antibacterial data,these potential drugs were compared with traditional antibiotics for their pharmacokinetic and pharmacodynamic characteristics in order to provide new ideas for the development of new drugs for CDI.