Unlocking the sporicidal potential of alcohol against Clostridium difficile

 描述(由申请人提供) 酒精洗手液是医疗机构手卫生的中流砥柱，对细菌孢子没有活性。酒精活性谱中的这种差距是至关重要的，因为形成孢子的厌氧菌艰难梭菌是医疗机构和社区的主要病原体。由于目前可用的杀孢子剂对皮肤的常规使用过于苛刻，我们研究了在酒精和其他皮肤消毒剂中诱导杀孢子活性的新方法，方法是将它们与改变孢子的药剂结合起来，使它们达到目标。我们已经证明，在体外和SKN上，酒精的酸化(pH 1.5到2)导致了对艰难梭菌的快速杀菌活性。这项建议的目标是开发具有最佳安全性和耐受性的酸化乙醇配方，并确定防止传播所需的孢子活力降低的程度。我们的中心假设是，将艰难梭菌在志愿者手中的孢子回收率降低97%或更多的改良酸化乙醇溶液将有效地防止医护人员手中的孢子转移。我们的第一个具体目标是确定酸化乙醇的修饰，在保持对艰难梭菌孢子的有效性的同时，优化皮肤的安全性和耐受性。为了实现这一目标，我们将研究增强酸化乙醇杀孢子活性的策略，包括增加离子强度、添加稀释过醋酸和温和升温，并在体外猪皮肤模型和人类志愿者手中测试优化溶液的有效性。我们的第二个具体目标是确定酸化乙醇溶液防止艰难梭菌孢子从医护人员手中转移的有效性。 为了实现这一目标，我们将在实验室模拟中确定酸化乙醇溶液在减少志愿者手中和医护人员手中的孢子转移方面的有效性。这一结果将是重要的，因为艰难梭菌是发病率和死亡率的主要原因，而且对开发杀灭孢子的手卫生产品有重要的未得到满足的需求。

 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.