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200万患者在医院感染，其中约10万人死亡。在美国，医院感染是导致死亡的主要原因，它导致住院时间、人类痛苦和医疗费用的大幅增加。这些感染中近一半与使用医疗器械有关，导尿管相关性尿路感染（UTI）是最常见的医院感染类型，占医院和疗养院感染的40%以上。大约95%的尿路感染与导尿管有关，这些导尿管相关的尿路感染估计每年的医院费用超过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，抗菌剂的使用导致耐药性模式，使留置导管感染更难治疗。通过涂覆导管，降低了感染的风险；然而，这一策略充其量只能延缓感染的发生。尽管预防策略取得了进展，但目前还没有明确的方法来预防导管相关的尿路感染。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，而不依赖于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“鲨鱼”微图案是最有效的。因此，本项目的总体目标是开发、验证并商业化使用Sharklet显微模式（基于鲨鱼皮肤独特的防污特性），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。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，而不依赖于传统的抗菌涂层或处理。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，而不依赖于传统的抗菌涂层或处理。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，而不依赖于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生长培养基和人工尿液中抑制尿源性大肠杆菌生物膜形成的有效性，为期14天；2)证明制造具有Sharklet图案腔外和腔内表面的导管样原型的可行性。第一阶段的成功将验证微图案表面的使用，以防止尿路病原体的生物膜生长，并将证明构建显示该图案的导管样原型的可行性。后续二期项目将设计用于开发试管原型的制造方法，并在体内猪模型上证明其有效性。第一阶段和第二阶段SBIR数据对于吸引“第三阶段”私营部门投资者和/或战略伙伴至关重要，我们已经在与他们讨论这项技术。因此，第三阶段的商业化工作将侧重于与医疗器械合作伙伴和分销商建立伙伴关系，特别是在导尿管市场。公共卫生相关性：在美国，每年约有500万患者插入3000万个导尿管，由于导尿管表面形成的细菌生物膜，这些患者中的每个人都有获得尿路感染的风险。目前抑制导管表面生物膜形成的策略价格昂贵，效果不佳，并且会引起严重的并发症，如毒副作用和多重耐药。该项目的总体目标是开发、验证和商业化使用Sharklet显微模式（基于鲨鱼皮肤独特的防污特性），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。