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200万患者在医院获得医院感染，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，它们导致住院时间、人类痛苦和医疗保健费用的大幅增加。这些感染中有近一半与医疗器械的使用有关，导管相关尿路感染（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UTI与导尿管有关，这些导管相关的UTI估计每年的医院费用超过4亿美元。目前预防细菌性UTI的范例是引入抗微生物剂以降低与生物膜形成相关的细菌浓度。然而，使用抗菌药物导致耐药模式，使留置导管感染更难治疗。通过涂层导管，感染的风险降低;然而，这种策略充其量只能延迟感染发作。尽管在预防策略方面取得了进展，但目前还没有明确的方法来预防导管相关性UTI。因此，Sharklet Technologies提出开发一种新型导管设计，能够持续抑制细菌生物膜形成，而不依赖于传统的抗菌涂层或处理。初步研究表明，聚合物表面的微图案可以被设计成抑制细菌生物膜的生长，其中“小鲨鱼”的微图案是最有效的。因此，本项目的总体目标是开发、验证和商业化Sharklet显微模式（基于鲨鱼皮的独特生物膜特性）的使用，以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形成，不依赖于传统的抗菌涂层或处理。提出了一种能够持续抑制细菌生物膜形成的新型导管设计的开发，其不依赖于传统的抗微生物涂层或处理。提出了一种能够持续抑制细菌生物膜形成的新型导管设计的开发，其不依赖于传统的抗微生物涂层或处理。阶段I是1）验证Sharklet微图案化聚合物表面抑制尿路致病性大肠杆菌生物膜形成的有效性。大肠杆菌在生长培养基和人工尿液中培养14天，以及2）证明制造具有Sharklet图案的腔外和腔内表面的导管样原型的可行性。阶段I的成功将验证微图案化表面的使用以防止泌尿病原体的生物膜生长，并且将证明构建表现出图案的导管样原型的可行性。将设计后续II期项目，以开发管原型的制造方法，并证明体内猪模型的有效性。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/或战略合作伙伴至关重要，我们已经与他们讨论了这项技术。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合作关系，特别是导尿管市场。公共卫生相关性：在美国，每年大约有3000万根导尿管被插入500万名患者体内，由于在导尿管表面形成的细菌生物膜，这些患者中的每一个都有患尿路感染的风险。目前用于抑制导管表面上的生物膜形成的策略是昂贵的、无效的，并且引起严重的并发症，诸如毒副作用和多药耐药性。该项目的总体目标是开发、验证和商业化Sharklet显微模式（基于鲨鱼皮肤独特的生物膜特性）的使用，以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。