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

微图案表面可降低导管相关尿路感染的风险

• 批准号: 7744454
• 负责人: Shravanthi Reddy
• 金额: $ 16.84万
• 依托单位: SHARKLET TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7744454
• 关键词: Accounting; Address; Adverse effects; Affect; Animal Model; Antibiotic Prophylaxis; Antibiotic Therapy; Antibiotics; Area; Bacteria; Bacteriocides; Biocompatible Materials; Biological; Biological Assay; Categories; Catheters; Cause of Death; Cell Survival; Cessation of life; Characteristics; Chemicals; Chemistry; Clinical; Culture Media; Data; Development; Devices; Effectiveness; Elastomers; Environment; Exhibits; Family suidae; Goals; Growth; Health Care Costs; Hospital Costs; Hospital Nursing; Hospitals; Housing; Human; Image; In Vitro; Indwelling Catheter; Infection; Interferometry; Knowledge; Length of Stay; Letters; Light; Marketing; Measures; Medical Device; Methods; Metric; Microbial Biofilms; Microscopic; Modeling; Multi-Drug Resistance; Nosocomial Infections; Nursing Homes; Organism; Patient Care; Patients; Pattern; Phase; Polymers; Private Sector; Property; Publishing; Relative (related person); Research; Resistance; Resistance to infection; Risk; Sampling; Scanning; Scanning Electron Microscopy; Shark; Simulate; Skin; Small Business Innovation Research Grant; Solutions; Specific qualifier value; Surface; Technology; Testing; Tube; Urinary tract; Urinary tract infection; Urine; Uropathogen; Uropathogenic E. coli; Validation; Veterans; Work; antimicrobial; antimicrobial drug; base; catheter associated UTI; commercialization; design; drug resistant bacteria; economic evaluation; experience; falls; improved; in vitro Assay; in vivo; interest; manufacturing process; meetings; microorganism; next generation; novel; pathogenic bacteria; polydimethylsiloxane; prevent; prophylactic; prototype; public health relevance; research and development; response; scale up; soy; success; urinary

DESCRIPTION (provided by applicant): In the U.S. alone, nearly two million patients acquire a nosocomial infection in the hospital each year, and approximately 100,000 of them die. Nosocomial infections are a leading cause of death in the U.S., and they result in major increases in hospital stays, human suffering, and healthcare costs. Nearly half of these infections are associated with the use of a medical device, and catheter-associated urinary tract infection (UTI) is the most common type of nosocomial infection, accounting for over 40% of infections in hospitals and nursing homes. Some 95% of UTIs are associated with urinary catheters, and these catheter-associated UTIs account for an estimated annual hospital cost of more than $400 million. The current paradigm for preventing bacterial UTIs has been to introduce antimicrobial agents to reduce the concentrations of bacteria associated with biofilm formation. However, use of antimicrobial agents leads to resistance patterns that make indwelling catheter infections more difficult to treat. By coating the catheter, the risk of infection is reduced; however, this strategy at best only delays the infection onset. Despite advances in prophylactic strategies, there are currently no definitive methods to prevent catheter-associated UTI. Sharklet Technologies therefore proposes development of a novel catheter design capable of sustained inhibition of bacterial biofilm formation that does not rely on traditional antimicrobial coatings or treatments. Preliminary studies have shown that micro-patterns on polymer surfaces can be designed to inhibit bacterial biofilm growth-with the Sharklet" micro-pattern being the most effective. Therefore, the overall goal of this project is to develop, validate, and commercialize the use of the Sharklet microscopic pattern (based on the unique antifouling characteristics of shark skin) to inhibit bacterial biofilm formation on urinary catheters without the use of antimicrobial agents. The Specific Aims for proposes development of a novel catheter design capable of sustained inhibition of bacterial biofilm formation that does not rely on traditional antimicrobial coatings or treatments. proposes development of a novel catheter design capable of sustained inhibition of bacterial biofilm formation that does not rely on traditional antimicrobial coatings or treatments. proposes development of a novel catheter design capable of sustained inhibition of bacterial biofilm formation that does not rely on traditional antimicrobial coatings or treatments. Phase I are 1) to validate the effectiveness of the Sharklet micro-patterned polymer surface for inhibiting biofilm formation with uropathogenic E. coli in growth media and artificial urine over the course of 14 days, and 2) to prove the feasibility of fabricating catheter-like prototypes that exhibit Sharklet-patterned extraluminal and intraluminal surfaces. Phase I success will validate the use of micro- patterned surfaces to prevent biofilm growth of a uropathogen and will demonstrate the feasibility of constructing a catheter-like prototype exhibiting the pattern. A follow-on Phase II project will be designed to develop manufacturing methods for the tube prototypes and to demonstrate efficacy with an in vivo pig model. The Phase I and Phase II SBIR data will be essential in attracting the types of "Phase III" private-sector investors and/or strategic partners with whom we are already discussing this technology. Phase III commercialization efforts will therefore be focused on establishing partnerships with medical device partners and distributors-particularly those in the urinary catheter markets. PUBLIC HEALTH RELEVANCE: Some 30 million urinary catheters are inserted into 5 million patients in the U.S. each year, and each one of those patients is at risk for acquiring a urinary tract infection due to the bacterial biofilms that form on the catheter surface. Current strategies for inhibiting biofilm formation on the catheter surfaces are expensive, ineffective, and give rise to serious complications such as toxic side-effects and multi-drug resistance. The overall goal of this project is to develop, validate, and commercialize the use of the Sharklet microscopic pattern (based on the unique antifouling characteristics of shark skin) to inhibit bacterial biofilm formation on urinary catheters without the use of antimicrobial agents.

描述（由申请人提供）：仅在美国，每年就有近 200 万患者在医院发生院内感染，其中约 10 万人死亡。医院感染是美国死亡的主要原因，导致住院时间、人类痛苦和医疗费用大幅增加。其中近一半的感染与医疗器械的使用有关，导管相关尿路感染 (UTI) 是最常见的院内感染类型，占医院和疗养院感染的 40% 以上。约 95% 的尿路感染与导尿管有关，这些与导尿管相关的尿路感染每年造成的住院费用估计超过 4 亿美元。目前预防细菌性尿路感染的范例是引入抗菌剂来降低与生物膜形成相关的细菌浓度。然而，抗菌药物的使用会产生耐药性，从而使留置导管感染更难以治疗。通过对导管进行涂层，可以降低感染的风险；然而，这种策略最多只能延迟感染的发生。尽管预防策略取得了进展，但目前尚无确定的方法来预防导管相关性尿路感染。因此，Sharklet Technologies 建议开发一种新型导管设计，能够持续抑制细菌生物膜的形成，且不依赖传统的抗菌涂层或处理。初步研究表明，可以设计聚合物表面的微图案来抑制细菌生物膜的生长——其中“Sharklet”微图案最为有效。因此，该项目的总体目标是开发、验证和商业化使用Sharklet微图案（基于鲨鱼皮独特的防污特性）来抑制导尿管上细菌生物膜的形成 不使用抗菌剂。具体目标建议开发一种新型导管设计，能够持续抑制细菌生物膜的形成，且不依赖传统的抗菌涂层或治疗。建议开发一种新颖的导管设计，能够持续抑制细菌生物膜的形成，而不依赖于传统的抗菌涂层或治疗。提出开发一种新颖的导管设计，能够 持续抑制细菌生物膜形成，不依赖传统的抗菌涂层或处理。第一阶段是 1) 验证 Sharklet 微图案聚合物表面在 14 天的时间内抑制生长培养基和人工尿液中尿路致病性大肠杆菌生物膜形成的有效性，以及 2) 证明制造具有以下特性的导管样原型的可行性： 鲨鱼鳍图案的腔外和腔内表面。第一阶段的成功将验证使用微图案表面来防止尿路病原体生物膜生长，并将证明构建具有该图案的导管样原型的可行性。后续第二阶段项目将旨在开发管原型的制造方法，并通过体内猪模型证明其功效。一期及二期 II SBIR 数据对于吸引我们已经在讨论这项技术的“第三阶段”私营部门投资者和/或战略合作伙伴至关重要。因此，第三阶段的商业化工作将集中于与医疗器械合作伙伴和分销商建立合作伙伴关系，特别是导尿管市场的合作伙伴和分销商。公共卫生相关性：美国每年有 500 万名患者插入约 3000 万根导尿管，而这些患者中的每一位都处于 由于导管表面形成细菌生物膜，有发生尿路感染的风险。目前抑制导管表面生物膜形成的策略昂贵、无效，并且会引起严重的并发症，例如毒副作用和多重耐药性。该项目的总体目标是开发、验证 Sharklet 微观模式并将其商业化（基于独特的防污性能） 鲨鱼皮的特性）可在不使用抗菌剂的情况下抑制导尿管上细菌生物膜的形成。