Unlocking the sporicidal potential of alcohol against Clostridium difficile

 描述（由申请人提供） 酒精洗手液，在医疗机构的手卫生的支柱，没有对细菌孢子的活动。酒精活性谱中的这种差距至关重要，因为孢子形成厌氧菌艰难梭菌是医疗机构和社区中的主要病原体。由于目前可用的杀孢子消毒剂对皮肤的常规使用过于苛刻，我们已经研究了通过将它们与改变孢子以使它们到达其目标的试剂组合来诱导酒精和其他皮肤消毒剂中杀孢子活性的新方法。我们已经证明，酸化的醇（pH 1.5至2）的结果，快速杀孢子活性对C。艰难梭菌在体外和皮肤上。本提案的目标是开发具有最佳安全性和耐受性的酸化乙醇制剂，并确定预防传播所需的孢子活力降低程度。我们的中心假设是，减少C。艰难梭菌孢子在志愿者手上的回收率达到97%或更高将有效防止孢子从医护人员手中转移。我们的第一个具体目标是确定酸化乙醇的修饰，优化皮肤的安全性和耐受性，同时保持对C。艰难孢子为了实现这一目标，我们将研究提高酸化乙醇杀孢子活性的策略，包括增加离子强度，加入diluteperacetic酸，和温和的温度升高，并测试优化的解决方案在离体猪皮肤模型和人类志愿者手上的有效性。我们的第二个具体目标是确定酸化乙醇溶液防止C转移的有效性。艰难梭菌孢子从医护人员的手中。 为了实现这一目标，我们将确定酸化乙醇溶液在减少实验室模拟中志愿者手中和医护人员手中孢子转移方面的有效性。由于C.艰难梭菌是发病和死亡的主要原因，并且对于开发杀孢子手卫生产品存在重要的未满足的需求。

 DESCRIPTION (provided by applicant) Alcohol hand sanitizers, the mainstay of hand hygiene in healthcare settings, do not have activity against bacterial spores. This gap in the spectrum of activity of alcohol is of critical importance because the spore-forming anaerobe Clostridium difficile is a major pathogen in healthcare facilities and in the community. Because currently available sporicidal disinfectants are too harsh for routine use on skin, we have investigated the novel approach of inducing sporicidal activity in alcohol and other skin disinfectants by combining them with agents that alter the spore to allow them to reach their target. We have demonstrated that acidification of alcohols (pH 1.5 to 2) results in rapid sporicidal activity against C. difficile in vitro and on skn. The goal of this proposal is to develop formulations of acidified ethanol with optimal safety and tolerability and to determine the degree of reduction in spore viability that is necessary to prevent transmission. Our central hypothesis is that modified acidified ethanol solutions that reduce C. difficile spore recovery by 97% or more on hands of volunteers will be effective in preventing transfer of spores from the hands of healthcare personnel. Our first specific aim is to identify modifications of acidified ethanol that optimize safety and tolerability on skin while maintaining efficacy against C. difficile spores. To accomplish this aim, we will examine strategies to enhance the sporicidal activity of acidified ethanol, including increased ionic strength, addition of diluteperacetic acid, and mild temperature elevation, and test the effectiveness of optimized solutions in an ex vivo porcine skin model and on hands of human volunteers. Our second specific aim is to determine the effectiveness of acidified ethanol solutions for prevention of transfer of C. difficile spores from the hands of healthcare personnel. To accomplish this aim, we will determine the effectiveness of acidified ethanol solutions in reducing transfer of spores from hands of volunteers in lab simulations and from hands of healthcare personnel. The results will be significant because C. difficile is a major cause of morbidity and mortality and there is an important unmet need for development of sporicidal hand hygiene products.