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

基本信息

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
项目类别：
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

项目摘要

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抗菌剂来减少管表面的细菌定植。然而，这些策略尚未表现出一致的功效或广泛采用。一个主要问题是抗菌药物的使用会导致耐药性模式，从而使感染更难以治疗。因此，在这个多阶段 SBIR 项目下，Sharklet Technologies 建议通过开发、验证和商业化一种新型气管插管 (ETT) 设计来推进这一关键领域的最先进技术，该设计能够持续抑制生物膜，并且不依赖传统的抗生素涂层。这项新技术基于经过验证的Sharket 图案表面，该表面已在之前的 SBIR 资助下成功开发。第一阶段研究达到并超越了优化 Sharklet 模式的研究目标，并在富含粘蛋白的培养基和存在等加剧生物膜生长的条件下，使铜绿假单胞菌和 MRSA 的细菌生物膜覆盖率减少至少 50% (p<0.05)抗生素的亚致死浓度。这个多阶段 SBIR 项目的总体目标是进一步开发、验证和商业化仿生 Sharklet 微观模式的使用，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 微图案原型，以完成监管验证和验证测试； 2) 开展 FDA 认可的体外呼吸机-气管内-肺模型，以测试 Sharklet 微图案 ETT 原型对最常见 VAP 致病病原体临床分离株的定植和生物膜形成的抑制作用； 3) 在绵羊模型中证明微生物定植、生物膜形成和管腔阻塞减少； 4) 在马萨诸塞州总医院的外科 ICU 进行临床试点研究，以证明 ETT 定植、生物膜形成和管腔闭塞减少。我们还将提交包含所有 II 期数据的 510(k)，以获得设备级索赔。二期项目将由跨学科专家研发团队负责实施完成了第一阶段的工作，并且之前已经成功完成了 NIH 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具有 Sharklet 图案的内表面、外表面和袖口表面的 ETT 的扩大制造方法。第二阶段 SBIR 数据对于吸引和充分参与我们已经在讨论这项技术的行业合作伙伴至关重要（见信件）。