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: 8524918
• 负责人: Shravanthi Reddy
• 金额: $ 110.51万
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8524918
• 关键词: Accounting; Achievement; Address; Adoption; Animal Model; Antibiotics; Area; Bacterial Antibiotic Resistance; Biomimetics; Cause of Death; Clinical; Clinical Research; Complex; Cost Savings; Data; Death Rate; Development; Device Designs; Devices; Environmental air flow; Funding; General Hospitals; Goals; Growth; Hospital Costs; Hospitals; Hour; In Vitro; Incidence; Infection; Intensive Care Units; Intubation; Lead; Letters; Lung; Massachusetts; Mechanical ventilation; Medical; Methods; Microbial Biofilms; Microbiology; Microfluidics; Microscopic; Modeling; Modification; Molds; Mucins; Nosocomial Infections; Nosocomial pneumonia; Outcome; Patient Care; Patients; Pattern; Phase; Physiological; Pilot Projects; Pneumonia; Polyurethanes; Procedures; Pseudomonas; Pseudomonas aeruginosa; Relative (related person); Research; Resistance; Resistance to infection; Risk; Safety; Sheep; Silicones; Silver; Small Business Innovation Research Grant; Social Welfare; Solutions; Staging; Suction; Surface; Surgical Intensive Care; Symptoms; Technology; Testing; Time; Tube; United States National Institutes of Health; Ventilator; Work; antimicrobial; antimicrobial drug; base; biomaterial compatibility; clinically relevant; commercialization; cost; design; drug resistant bacteria; endotracheal; improved; in vivo; industry partner; manufacturing process; manufacturing scale-up; meetings; methicillin resistant Staphylococcus aureus; microbial; microbial colonization; mortality; new technology; next generation; novel; pathogen; phase 1 study; prevent; prototype; public health relevance; research and development; success; tool; trend; verification and validation

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 antimicrobial agents that reduce bacterial colonization on the tube surfaces. However, these strategies have not demonstrated consistent efficacy or widespread adoption. A major concern is the use of antimicrobial agents that lead to resistance patterns that make infections more difficult to treat. Under this multi-phase SBIR project, Sharklet Technologies therefore proposes to advance the state-of-the-art in this key area by developing, validating, and commercializing a novel endotracheal tube (ETT) design that is capable of sustained biofilm inhibition and that does not rely on traditional antibiotic coatings. This novel technology is based upon the proven Sharket-patterned surface that has been developed successfully under previous SBIR funding. Phase I studies met and exceeded research goals to optimize the Sharklet pattern and to obtain at least 50% reduction (p<0.05) of bacterial biofilm coverage of P. aeruginosa and MRSA in conditions that exacerbated biofilm growth such as mucin-rich media and presence of sub-lethal concentrations of antibiotics. The overall goal of this multi-phase SBIR project is to further develop, validate, and commercialize the use of the biomimetic Sharklet microscopic pattern to inhibit bacterial biofilm formation on the ETT surfaces without the use of antimicrobial agents. The Specific Aims for Phase II are to 1) manufacture prototypes of the Sharklet micro-pattern for completion of regulatory verification and validation testing; 2) carry out an FDA-recognized in vitro ventilator-endotracheal- lung model to test Sharklet micro-patterned ETT prototypes for inhibition of colonization and biofilm formation with clinical isolates of the most common VAP causative pathogens; 3) demonstrate reduced microbial colonization, biofilm formation, and lumen occlusion in a sheep model; and 4) carry out a clinical pilot study in the Massachusetts General Hospital's Surgical ICU to demonstrate reduced ETT colonization, biofilm formation and lumen occlusion. We will also submit a 510(k) with all of the Phase II data to obtain a device-level claim. The Phase II project will be carried out by the expert interdisciplinary R&D team that completed the Phase I work and that has completed successful Phase I and Phase II SBIR projects for NIH previously. Post-Phase II commercialization will involve scaled-up manufacturing methods for ETTs with Sharklet-patterned inner, outer, and cuff surfaces. The Phase II SBIR data will be essential in attracting and fully engaging industry partners with whom we are already discussing this technology (see letters).

说明(申请人提供)：呼吸机相关肺炎(VAP)是最昂贵和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。在美国，每年约有30万HAP患者接受治疗，估计每年的医院费用超过15亿美元。目前预防VAP的范例是实施患者护理捆绑实践，并使用抗菌剂来减少细菌在管子表面的定植。然而，这些战略并没有表现出一致的有效性或广泛采用。一个主要的担忧是抗菌剂的使用导致耐药模式，使感染更难治疗。因此，在这个多阶段的SBIR项目中，Sharklet Technologies建议通过开发、验证和商业化一种能够持续抑制生物膜且不依赖传统抗生素涂层的新型气管内管(ETT)设计，来推进这一关键领域的最先进技术。这项新技术是基于在之前的SBIR资助下成功开发的经过验证的锐利图案表面。第一阶段研究达到并超过了优化Sharklet模式和获得至少50%(p&lt；0.05)铜绿假单胞菌和耐甲氧西林金黄色葡萄球菌(MRSA)细菌生物膜覆盖率的研究目标，这些条件会加剧生物膜的生长，例如富含粘液的介质和存在亚致死浓度的抗生素。这一多阶段SBIR项目的总体目标是进一步开发、验证仿生鲨鱼显微图案并将其商业化，以在不使用抗菌剂的情况下抑制ETT表面细菌生物膜的形成。第二阶段的具体目标是1)制造Sharklet微模式原型，以完成监管验证和有效性测试；2)开展FDA认可的体外呼吸机-气管内-肺模型以测试Sharklet微模式ETT原型对最常见VAP病原体的定植和生物膜形成的抑制作用；3)在绵羊模型上展示微生物定植、生物被膜形成和管腔闭塞的减少；4)在马萨诸塞州总医院外科ICU进行临床先导研究，以证明ETT的定植、生物被膜形成和管腔闭塞的减少。我们还将提交包含所有第二阶段数据的510(K)计划，以获得设备级索赔。第二阶段项目将由专家跨学科研发团队进行， 完成了第一阶段的工作，并成功地完成了国家卫生研究院的第一阶段和第二阶段SBIR项目。第二阶段后的商业化将涉及扩大具有鲨鱼图案的内、外和袖口表面的ETT的制造方法。第二阶段的SBIR数据将对吸引和充分参与我们已经在与其讨论这项技术的行业合作伙伴至关重要(见信函)。