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: 8735176
• 负责人: Shravanthi Reddy
• 金额: $ 67.88万
• 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/8735176
• 关键词: Accounting; Achievement; Address; Adoption; Analysis of Variance; 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).

描述（由申请人提供）：呼吸机相关的肺炎（VAP）是最昂贵，第二大医院获得的感染（HAI），占医院获得的肺炎（HAP）的86％以上。在美国，每年约有30万例HAP患者接受治疗，估计年度医院费用超过15亿美元。当前用于预防VAP的范例是实施患者护理束实践，并使用减少管表面细菌定植的抗菌剂。但是，这些策略尚未表现出一致的功效或广泛采用。一个主要问题是使用抗菌剂，从而导致抗性模式，从而使感染更难治疗。因此，在这个多相SBIR项目下，鲨鱼技术提议通过开发，验证和商业化一种能够持续的生物膜抑制作用且能够通过开发，验证和商业化的新型气管导管（ETT）设计来推进该关键领域的最新面积。不依赖传统的抗生素涂料。这项新颖的技术基于在先前的SBIR资金下成功开发的已验证的Sharkarearp图案表面。第一阶段的研究达到并超出了研究目标，以优化鲨鱼模式，并在加剧生物膜生长（如富含粘液蛋白的培养基且存在）的条件下，至少降低了铜绿假单胞菌和MRSA的细菌生物膜覆盖率（p <0.05）（P <0.05）（P <0.05）。亚致致命浓度的抗生素。这个多相SBIR项目的总体目标是进一步开发，验证和商业化仿生鲨鱼显微镜模式在不使用抗菌剂的情况下抑制ETT表面上细菌生物膜形成的情况。 II期的具体目的是1）制造鲨鱼微图案的原型，以完成调节验证和验证测试； 2）执行FDA识别的体外呼吸机 - 内齿气管模型，以测试鲨鱼微观图案ETT原型，以抑制定殖和生物膜形成，并具有最常见的临床分离株的临床分离株； 3）表明绵羊模型中的微生物定植，生物膜形成和腔内闭塞； 4）在马萨诸塞州综合医院的ICU进行临床试验研究，以证明ETT定殖，生物膜形成和腔内闭塞的降低。我们还将提交具有所有II期数据的510（k），以获得设备级的索赔。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，并完成了II阶段和II阶段SBIR项目的成功。相结合后的商业化将涉及具有鲨鱼形式内部，外部和袖口表面的ETT的扩展制造方法。第二阶段SBIR数据对于吸引和完全吸引的行业合作伙伴至关重要，我们已经与之讨论了这项技术（请参阅信件）。