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

描述（由申请人提供）：导管相关尿路感染（CANTI）是最常见的医院获得性感染，仅在美国每年就有超过100万例病例和超过5亿美元的医院费用。医疗保险和医疗补助服务中心最近的报销变化将直接将这一成本负担转嫁给医院，从而立即激励人们解决这一被忽视的护理问题。目前预防细菌性UTI的范例是引入抗菌剂以减少菌尿的发生。然而，抗菌剂产生的耐药性模式，使留置导管感染更难治疗。由于缺乏临床相关的支持数据，目前市场上没有抗菌导管得到CDC/APIC的认可。因此，Sharklet Technologies提出进一步开发一种新型Foley导管设计，该设计可抑制细菌定植，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微图案聚合物表面抑制细菌生物膜生长的可行性，为更大的第二阶段项目奠定了基础，该项目旨在充分原型化并展示Sharklet技术的潜力。该多阶段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，这将减少TBI。在第一阶段，Sharklet研发团队通过在体外测试三种Sharklet微图案相对于光滑表面，并通过在腔外和腔内表面成功制造具有Sharklet图案的硅胶管原型，减少尿路致病性大肠杆菌的定植，证明了这一新概念。基于这一成功，II期工作将集中在以下三个目标：首先，将体外疗效试验扩展到三个额外的相关尿路病原体，并在体外膀胱模型中测试细菌迁移的抑制作用。其次，Sharklet图案的Foley导管将通过我们的OEM合作伙伴Medical Components Inc.生产。制造的导管将接受标准试验，以确保其符合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试验，以获得FDA 510（k）申报的器械声明，该申报将在第II阶段结束时提交。第三，第二阶段将结束一项初步临床研究，以评价Sharklet图案Foley导管抑制导管表面细菌迁移的能力。本研究将是一项具有统计学效力的临床试验的不可或缺的先驱，以确认Sharklet Foley导管降低TBI的能力。第二阶段的成功将为临床医生/医院提供急需的工具，以改善患者护理，并通过Sharklet Foley导管减少感染负担来节省大量成本。第二阶段的数据对于吸引“第三阶段”投资者/行业合作伙伴至关重要，这些投资者/行业合作伙伴需要完成所需的开发/批准工作，并最终将这项新技术商业化。 公共卫生相关性：导管相关性尿路感染（CANTI）是最常见的医院获得性感染，仅在美国每年就导致显著的患者挫折、不适和超过5亿美元的医疗费用。凭借其成功的第一阶段SBIR工作，Sharklet Technologies证明了其新的Sharklet”微图案概念（基于鲨鱼皮）在Foley导管制造中的可行性，该概念可在不使用抗菌涂层或处理的情况下抑制细菌定植。Sharklet团队现在提出了一个第二阶段项目，以充分原型化并证明Sharklet Foley导管的有效性，为最终商业化一种新产品所需的FDA许可做准备，该产品将大大减少PADI的发生。

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.