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Inhibition of spores to prevent the recurrence of Clostridioides difficile infection - A possibility or an improbability?
Journal of Microbiology, Immunology and Infection ( IF 7.4 ) Pub Date : 2021-06-26 , DOI: 10.1016/j.jmii.2021.06.002
Chun-Wei Chiu , Pei-Jane Tsai , Ching-Chi Lee , Wen-Chien Ko , Yuan-Pin Hung

Clostridioides difficile is one of the most common nosocomial gastrointestinal pathogens, and recurrence is a problematic issue because approximately 20–30% of patients experience at least one episode of recurrence, even after treatment with a therapeutic drug of choice for C. difficile infection (CDI), such as vancomycin. CDI recurrence has a multifactorial complex mechanism, in which gut microbiota disruption coincident with viable C. difficile spores, is considered the most important factor. The effectiveness of an anti-C. difficile antimicrobial agent against CDI cannot guarantee its inhibitory effect on C. difficile spores and vice versa. However, an antimicrobial agent, such as fidaxomicin, which has a good inhibitory effect on both C. difficile vegetative cells and spores is assumed to not only treat CDI but also prevent its recurrence. Prolonged adherence to the exosporium has been proposed as a possible mechanism of inhibiting spores, and as a result, redesigning anti-C. difficile antimicrobial agents with the ability to adhere to the exosporium may provide another pathway for the development of anti-C. difficile spore agents. For example, vancomycin lacks an inhibitory effect against C. difficile spores, but a vancomycin-loaded spore-targeting iron oxide nanoparticle that selectively binds to C. difficile spores has been developed to successfully delay spore germination. Some new antimicrobial agents in phase II clinical trials, including cadazolid and ridinilazole, have shown exceptional anti-C. difficile and spore-inhibiting effects that can be expected to not only treat CDI but also prevent its recurrence in the future.



中文翻译:

抑制孢子以防止艰难梭菌感染复发 - 可能还是不可能?

艰难梭菌是最常见的医院胃肠道病原体之一,并且复发是一个问题,因为大约 20-30% 的患者经历至少一次复发,即使在使用艰难梭菌感染的首选治疗药物(CDI ) 治疗后也是如此),如万古霉素。CDI 复发具有多因素复杂机制,其中肠道微生物群破坏与可行的艰难梭菌孢子一致,被认为是最重要的因素。抗艰难梭菌抗微生物剂对 CDI 的有效性不能保证其对艰难梭菌的抑制作用孢子,反之亦然。然而,一种抗菌剂,如非达霉素,对艰难梭菌营养细胞和孢子都有良好的抑制作用,被认为不仅可以治疗 CDI,还可以防止其复发。已提出延长对外壁的粘附作为抑制孢子的可能机制,因此,重新设计能够粘附到外壁的抗艰难梭菌抗菌剂可能为开发抗艰难梭菌提供另一条途径孢子剂。例如,万古霉素对艰难梭菌孢子缺乏抑制作用,但载有万古霉素的孢子靶向氧化铁纳米颗粒可选择性地与艰难梭菌结合孢子已被开发用于成功地延迟孢子萌发。一些处于 II 期临床试验的新型抗菌药物,包括卡达唑胺和利地尼唑,已显示出卓越的抗艰难梭菌和抑制孢子的作用,预计不仅可以治疗 CDI,而且可以防止其在未来的复发。

更新日期:2021-06-26
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