Micro-patterned Surfaces for Reducing the Risk of Ventilator-Associated Pneumonia

用于降低呼吸机相关肺炎风险的微图案表面

• 批准号: 8199530
• 负责人: Shravanthi Reddy
• 金额: $ 21.58万
• 依托单位: SHARKLET TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8199530
• 关键词: Accounting; Address; Animal Model; Antibiotics; Bacterial Antibiotic Resistance; Bacterial Infections; Biomimetics; Cause of Death; Clinical; Culture Media; Data; Death Rate; Device Designs; Drug resistance; Ensure; Environment; Goals; Hospital Costs; In Vitro; Incidence; Infection; Intensive Care Units; Intubation; Lead; Marketing; Mechanical ventilation; Medical; Medical Device; Methods; Microbial Biofilms; Microbial Drug Resistance; Microscopic; Modeling; Modification; Mucins; Mucous body substance; Multi-Drug Resistance; Nosocomial Infections; Nosocomial pneumonia; Patient Care; Patients; Pattern; Performance; Phase; Pneumonia; Polymers; Prevention; Private Sector; Protocols documentation; Pseudomonas aeruginosa; Publishing; Qualifying; Relative (related person); Research; Resistance; Resistance to infection; Risk; Safety; Simulate; Small Business Innovation Research Grant; Social Welfare; Solutions; Staphylococcus aureus; Surface; Technology; Testing; Time; Tracheostomy procedure; Tube; Tympanostomy; Ventilator; Work; antimicrobial; antimicrobial drug; clinically relevant; commercialization; cost; design; drug resistant bacteria; endotracheal; implantable device; improved; in vivo; in vivo Model; indexing; innovation; manufacturing scale-up; meetings; methicillin resistant Staphylococcus aureus; mortality; next generation; novel; pathogen; pathogenic bacteria; patient safety; prevent; research and development

DESCRIPTION (provided by applicant): Ventilator-associated pneumonia (VAP) is the most costly and second most common hospital-acquired infection (HAI), accounting for over 86% of hospital-acquired pneumonia (HAP). Some 300,000 HAP patients are treated annually in the U.S., at an estimated annual hospital cost of more than $1.5 billion. The current paradigm for preventing VAP has been to implement patient care bundle practices and to use endotracheal tube (ETT) technologies that reduce bacterial access to and colonization on the tube surfaces. However, these strategies do not offer sustained inhibition of bacterial biofilm that is associated with VAP; their limited duration of efficacy hampers their value-particularly for late-onset VAP, which is more often associated with drug-resistant microbial species. Additionally, use of antimicrobial agents leads to resistance patterns that make infections more difficult to treat. By coating the tube surface, the risk of infection is reduced; however, this strategy at best only delays the infection onset. There are currently no definitive methods to prevent late-onset VAP associated with multi-drug-resistant pathogens. Sharklet Technologies therefore proposes to develop a novel ETT design capable of sustained biofilm inhibition that does not rely on traditional antibiotic coatings. Preliminary studies have shown that micro-patterns on polymer surfaces can be designed to inhibit bacterial biofilm-with the Sharklet" micro-pattern being the most effective. Therefore, the overall goal of this multi-phase SBIR project is to develop, validate, and commercialize the use of the biomimetic Sharklet microscopic pattern to inhibit bacterial biofilm formation on the ETT lumen, cuff, and outer surfaces without the use of antimicrobial agents. The Specific Aims for Phase I are to 1) optimize performance of the Sharklet micro-pattern, and 2) test the most effective Sharklet micro-patterns for inhibition of biofilm formation with clinical isolates of the most common VAP causative pathogens in a mucin-modified growth media over the course of 14 days. (Previous projects have already proven the feasibility of manufacturing tubes with the Sharklet pattern on the inner or outer surfaces.) A follow-on Phase II project will be designed to develop scaled-up manufacturing methods for ETTs with Sharklet-patterned inner, outer, and cuff surfaces and to further demonstrate efficacy with an in vivo animal model. Additionally, Phase II will offer an opportunity to investigate a possible added benefit of a Sharklet-patterned ETT-reduced occlusion due to enhanced surface energy, which will be studied in an in vitro mucus occlusion model. The Phase I and Phase II SBIR data will be essential in attracting and fully engaging 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 ETT markets. PUBLIC HEALTH RELEVANCE: Every patient who receives mechanical ventilation via an endotracheal tube (ETT) is at risk for developing ventilator-associated pneumonia (VAP)-the second most common hospital-acquired infection, which has a high mortality rate and results in medical costs of some $1.5 billion annually in the U.S. alone. Given that an effective solution to this problem has not been developed, particularly for late-onset VAP, Sharklet Technologies, Inc., proposes to pursue the needed advance in the state-of-the-art by incorporating its Sharklet" microscopic pattern onto the ETT components to inhibit biofilm formation that leads to bacterial infections and to ultimately reduce the incidence of VAP. This multi-phase SBIR research effort is focused on developing/commercializing a Sharklet-patterned ETT that significantly augments current ETT designs with the goal of increasing patient welfare and safety while greatly reducing medical costs.

描述（由申请人提供）：呼吸机相关性肺炎 (VAP) 是最昂贵且第二常见的医院获得性感染 (HAI)，占医院获得性肺炎 (HAP) 的 86% 以上。美国每年约有 30 万名 HAP 患者接受治疗，估计每年的医院费用超过 15 亿美元。当前预防 VAP 的范例是实施患者护理捆绑实践并使用气管插管 (ETT) 技术来减少细菌进入和在管表面定植。然而，这些策略并不能持续抑制与 VAP 相关的细菌生物膜；它们有限的疗效持续时间限制了它们的价值，特别是对于晚发型 VAP，这通常与耐药微生物物种有关。此外，抗菌药物的使用会导致耐药性，使感染更难治疗。通过管表面涂层，降低感染风险；然而，这种策略最多只能延迟感染的发生。目前尚无确定的方法来预防与多重耐药病原体相关的迟发性 VAP。 因此，Sharklet Technologies 提议开发一种新型 ETT 设计，能够持续抑制生物膜，且不依赖传统的抗生素涂层。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，其中“Sharklet”微图案最为有效。因此，这个多阶段SBIR项目的总体目标是开发、验证和商业化仿生Sharklet微图案的使用，以抑制ETT管腔、袖带和外部的细菌生物膜形成。 不使用抗菌剂的表面。 第一阶段的具体目标是 1) 优化 Sharklet 微图案的性能，2) 在 14 天的时间里，在粘蛋白修饰的生长培养基中使用最常见的 VAP 致病病原体的临床分离株来测试最有效的 Sharklet 微图案抑制生物膜形成的效果。 （之前的项目已经证明了制造的可行性 内表面或外表面上具有 Sharklet 图案的管。）后续第二阶段项目将旨在开发具有 Sharklet 图案内表面、外表面和袖带表面的 ETT 的放大制造方法，并进一步证明体内动物模型的功效。此外，第二阶段将提供一个机会来研究 Sharklet 图案 ETT 减少闭塞由于表面能增强而可能带来的额外好处，这将是 在体外粘液闭塞模型中进行了研究。第一阶段和第二阶段的 SBIR 数据对于吸引和充分参与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设备合作伙伴和分销商建立合作伙伴关系，特别是 ETT 市场的合作伙伴和分销商。 公共卫生相关性：每位通过气管插管 (ETT) 接受机械通气的患者都有患呼吸机相关性肺炎 (VAP) 的风险，这是第二常见的医院获得性感染，死亡率很高，仅在美国每年就造成约 15 亿美元的医疗费用。鉴于尚未开发出针对这一问题的有效解决方案，特别是对于迟发性 VAP，Sharklet Technologies, Inc. 提议通过将其 Sharklet”微观模式整合到 ETT 组件上来追求最先进的技术进步，以抑制导致细菌感染的生物膜形成，并最终降低 VAP 的发病率。这项多阶段 SBIR 研究工作的重点是开发/商业化 Sharklet 图案的 ETT 显着增强了当前的 ETT 设计，旨在提高患者福利和安全，同时大大降低医疗成本。