Novel hand hygiene product to remove Clostridioides difficile spores

7. 项目总结/摘要 目前，艰难梭菌在美国造成的院内感染和死亡人数比任何其他病原体都多，并且 工业化国家成年人中与医疗相关的腹泻的最重要原因。 2017年， 估计有 462,100 例与医疗保健和社区相关的艰难梭菌感染病例 美国，20,500 人在医院死亡。在一项随机试验中，肥皂和水清洗 30 秒可减少 但并没有消除 CDI 患者或无症状艰难梭菌携带者的手部污染，而 酒精手部卫生没有效果。医护人员的手经常被 C. 艰难梭菌孢子，但用肥皂和水洗手效果有限，而含酒精的洗手液 消毒剂对孢子基本上没有功效。因此，存在一个重要的未满足的发展需求 减少手上孢子负担的有效策略。考虑到不被认可的担忧 无症状携带者对传播的贡献很大，迫切需要全面的 适用于直接护理 CDI 患者的方法，并且更普遍地适用于所有手部患者 卫生。 我们开发了一种实用且高度创新的方法来通过开发来满足这一需求 一种杀孢子洗手液，可有效显着减少皮肤上的艰难梭菌孢子。我们的洗手 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) 通过物理和机械手段显着增强从皮肤上去除艰难梭菌孢子的能力 与传统的肥皂和水相比。洗涤过程中皮肤表面产生的剪切应力 与传统肥皂和水相比，MSF 高出 10 至 100 倍。 重要的是，我们最近发现，当微结构流体包含新颖的 和中性 pH 值下对皮肤安全的杀孢子成分，我们能够将艰难梭菌孢子减少约 3.5 个对数 根据综合测试，30 秒内即可从猪皮中提取。这一发现具有重大意义 原则上，对传统肥皂和水的改进应能高度保证预防 传播艰难梭菌感染。这一新发现意义重大，因为目前的酒精类洗手液 对艰难梭菌孢子无效。该项目的重点是：1）优化并最终确定 MSF 手 洗涤配方基于已建立的皮肤模型的测试，目标是实现 >3 log 减少 艰难梭菌孢子和来自皮肤的重要 HAI 感染； 2) 生产无国界医生组织洗手产品 GMP，进行兼容性/稳定性研究并制定质量控制要求； 3）测试 MSF 洗手液在皮肤上的安全性和耐受性符合 FDA 的要求。

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.