Novel hand hygiene product to remove Clostridioides difficile spores

7.项目总结/摘要 C.艰难梭菌现在在美国引起的医院感染和死亡比任何其他病原体都多， 这是工业化国家成人中与医疗保健相关的腹泻的最重要原因。在2017年， 估计有462，100名与医疗保健和社区相关的C。艰难感染病例， 美国，20，500例住院死亡。在一项随机试验中，用肥皂和水洗涤30秒， 但不能消除CDI或无症状携带C.艰难，而 酒精洗手没有效果。医护人员的手经常被C。 艰难的孢子，但用肥皂和水洗手只有适度的功效，和酒精为主的手 消毒剂对孢子基本上没有效力。因此，有一个重要的发展需要没有得到满足 有效的策略来减少手上的孢子负担。考虑到未被承认的 无症状携带者对传播有很大贡献，迫切需要全面的 方法适用于直接护理CDI患者的人员，并且更普遍地适用于所有手 卫生。 我们制定了一个切实可行和高度创新的方法，通过发展 一种杀孢子洗手液，可以有效地减少C。皮肤上的艰难孢子。我们的洗手液 该配方基于使用由微纤化纤维素制成的新型微结构流体（MSF 这显着增强了C的去除。通过物理和机械方法从皮肤上分离艰难孢子 与传统的肥皂和水相比。在用洗涤剂洗涤期间在皮肤表面处产生的剪切应力 与传统的肥皂和水相比，MSF高出10到100倍。 重要的是，我们最近发现，当微结构化流体被制成包含新颖的纳米粒子时， 和中性pH下皮肤安全的杀孢子成分，我们能够实现C.艰难梭菌孢子 从猪皮中分离出来的蛋白质。这一发现构成了一个重要的 对传统肥皂和水的改进，原则上，应该导致高保证防止 发送C.艰难感染这一新发现意义重大，因为目前的酒精洗手液 对C无效。艰难孢子本项目的重点是：1）优化和最终确定MSF手 基于用已建立的皮肤模型进行的测试的洗涤制剂，目标是实现> 3个对数减少 梭区分孢子和来自皮肤的重要HAI感染; 2）在以下条件下制造MSF洗手产品 GMP，进行相容性/稳定性研究并制定质量控制要求;以及3）测试 FDA要求的MSF洗手液在皮肤上的安全性和耐受性。

7. Project Summary/Abstract C. difficile now causes more hospital-onset infections and deaths in the US than any other pathogen and is the most important cause of healthcare-associated diarrhea among adults in industrialized countries. In 2017, there were an estimated 462,100 combined healthcare- and community-associated C. difficile infection cases in the US, and 20,500 in-hospital deaths. In a randomized trial, soap and water washing for 30 seconds reduced but did not eliminate hand contamination in patients with CDI or asymptomatic carriage of C. difficile, whereas alcohol hand hygiene had no effect. The hands of healthcare workers frequently become contaminated with C. difficile spores, but hand washing with soap and water has only modest efficacy, and alcohol-based hand sanitizers have essentially no efficacy against spores. Thus, there is an important unmet need for development of effective strategies to reduce the burden of spores on hands. Given the concern that unrecognized asymptomatic carriers contribute significantly to transmission, there is an urgent need for comprehensive approaches applicable to persons who directly care for CDI patients, and also more generally for all hand hygiene. We have developed a practical and highly innovative approach to meet this need through the development of a sporicidal hand wash that is effective in significantly reducing C. difficile spores on skin. Our hand wash formulation is based on the use of a new class of microstructured fluid (MSF) made with microfibrillated cellulose which significantly enhances the removal of C. difficile spores from skin by physical and mechanical means compared to traditional soap and water. The shear stresses generated at the skin surface during washing with MSF are 10 to 100 times higher when compared to what can be obtained with traditional soap and water. Importantly, we have recently discovered that when the microstructured fluid is made with the inclusion of novel and skin-safe sporicidal ingredients at neutral pH, we are able to achieve ∼3.5 log reduction of C. difficile spores from porcine skin in 30 seconds according to comprehensive testing. This discovery constitutes a significant improvement over conventional soap and water, and in principal, should result in high assurance prevention of transmitting C. difficile infection. This new discovery is significant since current alcohol-based hand sanitizers are ineffective against C. difficile spores. This project is focused on: 1) optimizing and finalizing the MSF hand washing formulation based on testing with an established skin model with the goal of achieving >3 log reduction of C. diff spores and important HAI infections from skin; 2) manufacturing the MSF hand wash product under GMP, performing compatibility/stability studies and developing quality control requirements; and 3) testing the safety and tolerability of the MSF hand wash on skin as required by FDA.