Prevention of Clostridium difficile-associated disease

描述（由申请人提供）：艰难梭菌相关疾病（CDAD）是常规抗生素治疗后的医院获得性问题。其影响可能超过任何其他医院感染。产生毒素的病原体的孢子对抗生素具有高度耐药性，因此当广谱口服抗生素杀死竞争细菌时，它们会在肠道内过度生长。难辨梭菌孢子对医院常用消毒剂具有耐药性，从而污染医院环境，为患者，特别是极易感染的老年人提供了接种剂。疾病症状包括腹泻和假膜性结肠炎。治疗方法为甲硝唑或万古霉素，但复发率一般超过20%。最近传播了一种更具攻击性的菌株，其产生毒素a和B的量分别是其16倍和23倍，这是一种二元毒素，对氟喹诺酮类药物具有耐药性，孢子产量高，导致死亡率超过16%。拟议的研究是为常规使用的抗生素开发佐剂，从而减少肠道中孢子的数量，从而抑制艰难梭菌的萌发和生长。治疗应防止艰难梭菌在胃肠道过度生长，使竞争细菌在肠道定植，抑制艰难梭菌和CDAD的生长。公共卫生相关性：艰难梭菌相关疾病（CDAD）是由抗生素治疗引起的，已成为最昂贵和最具破坏性的医院获得性感染。这项SBIR研究提出通过使用抗生素佐剂来预防CDAD。

DESCRIPTION (provided by applicant): Clostridium difficile-associated disease (CDAD) is a hospital-acquired problem following routine antibiotic treatment. Its impact may exceed that of any other nosocomial infection. Spores of the toxin-producing pathogen are highly resistant to antibiotics and therefore overgrow the gut when broad-spectrum oral antibiotics kill off the competing bacteria. The C. difficile spores are resistant to common hospital disinfectants, thus contaminating the hospital environment and providing inoculum for infection of patients, especially the highly vulnerable elderly. Disease symptoms include diarrhea and pseudomembranous colitis. Treatment of the disease is with metronidazole or vancomycin, but relapse is commonly more than 20%. Recent spread of a more aggressive strain, that produces toxins A and B at 16 times and 23 times greater, a binary toxins, is resistant to fluoroquinolones, is hyper-productive of spores, and leads to mortality rates greater than 16%. The proposed research is to develop adjuvants for routinely used antibiotics, enabling reduction of numbers of spores in the gut and subsequently inhibiting the germination and growth of C. difficile. The treatment should prevent C. difficile overgrowth of the GI tract, allowing competing bacteria to colonize the gut and suppress the growth of C. difficile and CDAD. PUBLIC HEALTH RELEVANCE: Clostridium difficile-associated disease (CDAD) is caused by antibiotic treatment and has become the most costly and injurious hospital-acquired infection. This SBIR research proposes prevention of CDAD through the use of adjuvants with the antibiotics.