Micro-patterned surfaces for reducing the risk of catheter-associated UTI

描述（由申请人提供）：导尿管相关性尿路感染（CAUTI）是最常见的医院获得性感染，仅在美国每年就有超过100万例病例，医院费用超过5亿美元。最近医疗保险和医疗补助服务中心的报销变化将把这一成本负担直接转嫁到医院身上，从而产生了解决这一被忽视的护理方面的直接动力。目前预防细菌性尿路感染的范例是引入抗菌药物以减少细菌尿的发生。然而，抗菌剂产生的耐药模式使留置导管感染更难治疗。由于缺乏临床相关的支持数据，目前市场上还没有任何一种抗菌导管获得CDC/APIC的认可。因此，Sharklet Technologies建议进一步开发一种新的Foley导管设计，可以抑制细菌定植，并且不依赖于传统的抗生素涂层或治疗。我们的第一阶段SBIR工作证明了使用新型“Sharklet”微模式聚合物表面抑制细菌生物膜生长的可行性，为第二阶段更大的项目奠定了基础，该项目旨在完全原型化并展示Sharklet技术的潜力。这个多阶段SBIR项目的总体目标是将具有Sharklet微图案的硅胶Foley导管商业化，以减少CAUTI。在第一阶段，Sharklet研发团队通过测试三种相对于光滑表面的Sharklet微图案，以及成功地在腔外和腔内表面制造出带有Sharklet图案的硅胶管原型，来减少尿路致病性大肠杆菌的定殖，从而证明了这一新概念。基于这一成功，II期工作将集中于以下三个目标：首先，将体外功效测试扩展到另外三种相关的泌尿系统病原体，并在体外膀胱模型中测试细菌迁移的抑制作用。其次，鲨鱼图案的Foley导管将通过我们的OEM合作伙伴Medical Components Inc.生产。制造的导管将进行标准测试，以确保它们符合FDA的生物相容性和功能性能标准，以及重复的体外膀胱模型测试，以获得将在II期结束时提交的FDA 510(k)提交的设备声明。第三，II期将以一项试点临床研究结束，以评估鲨鱼图案Foley导管抑制导管表面细菌迁移的能力。这项研究将是一个完整的先驱，为统计支持的临床试验，以确认Sharklet Foley导管减少CAUTI的能力。二期试验的成功将为临床医生/医院提供一种急需的工具，以改善患者护理，并通过Sharklet Foley导管减少感染负担，大幅节省成本。第二阶段的数据对于吸引“第三阶段”投资者/行业合作伙伴完成所需的开发/批准工作并最终将这项新技术商业化至关重要。

DESCRIPTION (provided by applicant): Catheter-associated urinary tract infections (CAUTI) are the most common hospital- acquired infections, accounting for over one million cases and hospital costs of more than $500 million each year in the U.S. alone. Recent reimbursement changes from the Centers of Medicare and Medicaid Services will place this cost burden directly onto hospitals, creating an immediate incentive to address this neglected aspect of care. The current paradigm for preventing bacterial UTIs has been to introduce antimicrobial agents to reduce the occurrence of bacteriuria. However, antimicrobial agents produce resistance patterns that make indwelling catheter infections more difficult to treat. No antimicrobial catheter now on the market has been endorsed by either CDC/APIC due to a lack of clinically relevant supporting data. Sharklet Technologies therefore proposes to further develop a novel Foley catheter design that inhibits bacterial colonization and that does not rely on traditional antibiotic coatings or treatments. Our Phase I SBIR work proved the feasibility of using the novel Sharklet" micro-pattern polymer surface to inhibit bacterial biofilm growth-setting the stage for a larger Phase II project designed to fully prototype and demonstrate the potential for the Sharklet technology. The overall goal of this multi-phase SBIR project is to commercialize a silicone Foley catheter with the Sharklet micro-pattern that will reduce CAUTI. During Phase I the Sharklet R&D team demonstrated this new concept by reducing colonization of uropathogenic Escherichia coli with in vitro via testing of three Sharklet micro-patterns relative to a smooth surface and by successfully fabricating silicone tube prototypes with the Sharklet pattern on the extraluminal and intraluminal surfaces. Based on that success, Phase II work will focus on the following three Aims: First, to extend in vitro efficacy testing to three additional, relevant uropathogens and to test inhibition of bacterial migration in an in vitro bladder model. Second, Sharklet-patterned Foley catheters will be manufactured via our OEM partner, Medical Components Inc. The manufactured catheters will undergo standard testing to ensure they meet FDA criteria for biocompatibility and functional performance, as well as repeated in vitro bladder model testing to obtain device claims for the FDA 510(k) submission that will be made at the end of Phase II. Third, Phase II will conclude with a pilot clinical study to evaluate the ability of the Sharklet-patterned Foley catheter to inhibit bacterial migration on the catheter surface. This study will be an integral precursor to a statistically powered clinical trial for confirming the Sharklet Foley catheter's ability to reduce CAUTI. Phase II success will set the stage for providing a much-needed tool for clinicians/hospitals to improve patient care and reap significant cost savings with the reduced burden of infection enabled by the Sharklet Foley catheter. The Phase II data is critical for engaging the "Phase III" investors/industry partners needed to complete the required development/approval work and to ultimately commercialize this new technology. PUBLIC HEALTH RELEVANCE: Catheter-associated urinary tract infections (CAUTI) are the most common hospital- acquired infections, resulting in significant patient setbacks, discomfort, and medical costs of over half a billion dollars annually in the U.S. alone. With its successful Phase I SBIR work, Sharklet Technologies proved the feasibility of its new Sharklet" micro-pattern concept (based on shark skin) for Foley catheter manufacture that inhibits bacterial colonization without the use of antimicrobial coatings or treatments. The Sharklet team now proposes a Phase II project to fully prototype and demonstrate efficacy of the Sharklet Foley catheter in preparation for the FDA clearance required to ultimately commercialize a new product that will substantially reduce the occurrence of CAUTI.