Giles Joanna, Roberts April
MicroPharm Ltd, Newcastle Emlyn, United Kingdom.
Toxins Group, National Infection Service, Public Health England, Porton Down, United Kingdom.
Adv Protein Chem Struct Biol. 2022;129:215-245. doi: 10.1016/bs.apcsb.2021.11.003. Epub 2022 Jan 7.
The most common world-wide cause of antibiotic-associated infectious diarrhea and colitis is the toxin producing bacterium, Clostridioides difficile (C. difficile). Here we review the background and characteristics of the bacterium and the toxins produced together with the epidemiology and the complex pathogenesis that leads to a broad clinical spectrum of disease. The review describes the difficulties faced in obtaining a quick and accurate diagnosis despite the range of sensitive and specific diagnostic tools available. We also discuss the problem of disease recurrence and the importance of disease prevention. The high rates of infection recurrence mean that treatment strategies are constantly under review and we outline the diverse treatment options that are currently in use and explore the emerging treatment options of pulsed antibiotic use, microbial replacement therapies and the use of monoclonal antibodies. We summarize the future direction of treatment strategies which include the development of novel antibiotics, the administration of oral polyclonal antibody formulations, the use of vaccines, the administration of competitive non-toxigenic spores and the neutralization of antibiotics at the microbiota level. Future successful treatments will likely involve a combination of therapies to provide the most effective and robust approach to C. difficile management.
全球范围内，抗生素相关性感染性腹泻和结肠炎最常见的病因是产毒素细菌艰难梭菌（C. difficile）。在此，我们综述该细菌及其产生的毒素的背景和特征，以及导致广泛疾病临床谱的流行病学和复杂发病机制。本综述描述了尽管有一系列敏感且特异的诊断工具，但在获得快速准确诊断方面所面临的困难。我们还讨论了疾病复发问题以及疾病预防的重要性。感染复发率高意味着治疗策略不断受到审视，我们概述了目前正在使用的多种治疗选择，并探讨了脉冲式抗生素使用、微生物替代疗法和单克隆抗体使用等新兴治疗选择。我们总结了治疗策略的未来方向，包括新型抗生素的研发、口服多克隆抗体制剂的给药、疫苗的使用、竞争性非产毒孢子的给药以及在微生物群水平对抗生素的中和。未来成功的治疗可能需要多种疗法的组合，以提供针对艰难梭菌管理的最有效和有力方法。
