Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan.
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Medical College, Tainan, Taiwan.
J Microbiol Immunol Infect. 2021 Dec;54(6):1011-1017. doi: 10.1016/j.jmii.2021.06.002. Epub 2021 Jun 26.
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.
艰难梭菌是最常见的医院获得性胃肠道病原体之一，复发是一个问题，因为大约 20-30%的患者在经历一次复发后，甚至在使用艰难梭菌感染（CDI）的治疗药物（如万古霉素）治疗后，至少会经历一次复发。CDI 的复发有一个多因素的复杂机制，其中肠道微生物群的破坏与存活的艰难梭菌孢子同时发生，被认为是最重要的因素。抗艰难梭菌抗菌药物对 CDI 的有效性并不能保证其对艰难梭菌孢子的抑制作用，反之亦然。然而，一种抗菌药物，如非达霉素，对艰难梭菌的营养细胞和孢子都有很好的抑制作用，不仅可以治疗 CDI，还可以预防其复发。延长对外孢囊的附着被认为是抑制孢子的一种可能机制，因此，重新设计具有附着外孢囊能力的抗艰难梭菌孢子的抗菌药物可能为开发抗艰难梭菌孢子药物提供另一种途径。例如，万古霉素对艰难梭菌孢子没有抑制作用，但已经开发出一种载有万古霉素的靶向艰难梭菌孢子的氧化铁纳米颗粒，它可以选择性地结合艰难梭菌孢子，成功地延迟孢子萌发。一些处于 II 期临床试验阶段的新型抗菌药物，包括卡他唑利和利奈唑胺，显示出了出色的抗艰难梭菌和抑制孢子的效果，有望不仅治疗 CDI，还能预防其未来的复发。
