Novel Anti-infective and Anti-thrombotic Micro-patterned Central Venous Catheter

新型抗感染抗血栓微图案中心静脉导管

• 批准号: 8251007
• 负责人: Shravanthi Reddy
• 金额: $ 20.3万
• 依托单位: SHARKLET TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8251007
• 关键词: Accounting; Address; Adherence; Adhesions; Americas; Animal Model; Anti-Bacterial Agents; Anti-Infective Agents; Anticoagulants; Antimicrobial Resistance; Area; Bacteria; Blood; Blood Clot; Blood Platelets; Blood Tests; Blood Vessels; Blood coagulation; Caring; Catheter-related bloodstream infection; Catheterization; Catheters; Cause of Death; Cessation of life; Clinical Trials Design; Collaborations; Communities; Contracts; Cost Savings; Critical Illness; Data; Development; Devices; Drug Compounding; Effectiveness; Environment; Enzyme-Linked Immunosorbent Assay; Event; Fibrinolytic Agents; Genus staphylococcus; Goals; Health Care Costs; Healthcare; Heparin; Hospital Costs; Hospital Mortality; Hospitals; Human; In Vitro; Incidence; Infection; Lead; Length of Stay; Light; Medical; Medical Device; Methods; Microscopic; Morbidity - disease rate; Nosocomial Infections; Nutrient; Organism; Outcome; Patient Care; Patients; Pattern; Performance; Phase; Physiological; Plasma; Polyurethanes; Private Sector; Process; Production; Proteins; Recovery; Research; Risk; Safety; Sampling; Severities; Silicones; Small Business Innovation Research Grant; Solutions; Source; Staging; Staphylococcus aureus; Stress; Surface; Suspension substance; Suspensions; Technology; Testing; Thrombin; Thrombocytopenia; Thromboembolism; Thrombosis; Time; Translating; United States Centers for Medicare and Medicaid Services; Validation; Venous; Whole Blood; Work; antimicrobial; antimicrobial drug; catheter related infection; commercialization; cost; improved; in vitro testing; in vivo; manufacturing process; mortality; next generation; novel; pathogen; patient safety; prevent; prospective; research and development; success

DESCRIPTION (provided by applicant): Healthcare-acquired infections are increasing in rate and severity; they present a significant challenge to the medical community as a top-ten leading cause of death in the U.S. Nearly half of these infections are associated with the use of a medical device. Central venous catheters (CVCs) are responsible for approximately 90% of all catheter-related bloodstream infections (CRBSIs). The resulting 300,000 infections are associated with as many as 28,000 deaths per year in America alone. CRBSIs prolong hospital stays, induce human suffering, and magnify healthcare costs (up to $2.68 billion). Infection is four times more likely to occur in patients with catheter-related thrombosis (CRT), and up to 67% of patients with CVC develop CRT. In addition to increasing the risk of infection, CRT is associated with thromboembolic conditions that are the leading cause of in-hospital mortality in the U.S. The current paradigm for preventing CRBSI and CRT has been to introduce antimicrobial or antithrombotic agents to reduce the concentrations of bacteria or platelets on the catheter surface. The activity of antimicrobial catheters can be overwhelmed by high concentrations of bacteria, and their efficacy is primarily limited to the initial elution spike of agents in the first few days. Anticoagulant-coated catheters can suffer from contamination issues and have not been shown to reduce mortality rates associated with thrombotic events. Sharklet Technologies Inc. (STI) aims to demonstrate the feasibility of integrating our proprietary Sharklet micro-pattern (Sharklet MP) into catheter surfaces to ultimately reduce CVC-related infection and to validate the ability of the Sharklet surface to prevent platelet adhesion leading to thrombosis. STI's preliminary data demonstrates that the Sharklet MP inhibits bacterial colonization as well as platelet adhesion and activation-thereby offering a dual capacity to prevent CRBSI and CRT. The overall goal of this multi-phase SBIR project is to develop, validate, and commercialize the application of the Sharklet MP surface on a nextgeneration anti-infective, anti-thrombotic CVC. The specific Phase I goal is to show the efficacy of the Sharklet MP by pursuing the following Aims: 1) prove that we can retard pathogenic Staphylococci colonization on Sharklet surfaces in a vascular environment, and 2) prove that we can decrease platelet adhesion and subsequent thrombin formation on Sharklet surfaces compared to un-patterned control surfaces. Phase II work will then focus on validation with an in vivo animal model, in vitro testing with other pathogens, durability testing against deleterious drug compounds, and manufacturing methods for the Sharklet CVC. Phase I & II results are essential for Phase III collaboration with private-sector partners/investors with whom we are already discussing this application. The potential impact of a successful multi-phase SBIR will be the production of a new Sharklet CVC that will allow clinicians/hospitals to improve patient care and reap significant cost savings by substantially reducing the major burden of nosocomial infections and in-hospital mortality due to thrombosis. PUBLIC HEALTH RELEVANCE: The most serious and common complications of central venous catheters (CVC) are catheter-related bloodstream infection (CRBSI), which accounts for more than 30% of the deaths that result from hospital-acquired infections and incurs medical costs as high as $2 billion annually in the U.S. alone, and catheter-related thrombosis (CRT), which can lead to thromboembolism, a major contributor to in-hospital mortality. Unlike impregnation of the CVC surface with antimicrobial agents or coating with anticoagulants that have severe limitations in addressing CRBSI and CRT, a next-generation solution that incorporates the non-kill Sharklet" microscopic pattern onto the catheter surface can inhibit both bacterial colonization that leads to CRBSI and platelet adhesion that leads to CRT, thereby improving patient care. This multi-phase research effort will help develop and commercialize an anti-infective, anti-thrombotic CVC that has the Sharklet micro- pattern integrated on the catheter surface with the objective of improving patient safety by reducing in-hospital infection, morbidity, mortality, and costs.

描述（申请人提供）：医疗保健获得的感染率和严重程度正在增加；他们对医学界提出了重大挑战，因为美国几乎一半的感染与使用医疗装置有关。中央静脉导管（CVC）造成了所有与导管相关的血液感染（CRBSIS）的约90％。仅在美国，每年的300,000次感染就会每年多达28,000人死亡。 CRBSIS延长医院，诱发人类痛苦并扩大医疗保健费用（高达26.8亿美元）。与导管相关血栓形成（CRT）患者发生感染的可能性高四倍，而CVC患者中有67％的感染发生了CRT。除了增加感染的风险外，CRT还与美国目前预防CRBBSI和CRT的范式有关的血栓栓塞状况，这是降低抗菌剂或抗强调剂的主要原因，以降低导管表面上的细菌或血小板的浓度。抗菌导管的活性可能被高浓度的细菌淹没，并且它们的功效主要限于最初几天的初始洗脱峰值。抗凝剂涂层的导管可能会遭受污染问题，并且没有被证明会降低与血栓事件相关的死亡率。 Sharklet Technologies Inc.（STI）旨在证明将我们的专有鲨鱼微图案（鲨鱼MP）整合到导管表面上的可行性，以最终降低与CVC相关的感染并验证鲨鱼表面以防止血小板粘附导致血栓形成的能力。 STI的初步数据表明，鲨鱼MP抑制细菌定殖，血小板粘附和激活 - 提供双重能力以防止CRBSI和CRT。这个多相SBIR项目的总体目标是开发，验证和商业化鲨鱼MP表面在下一代抗感染的抗凝血CVC上的应用。特定阶段的目标是通过追求以下目的来显示鲨鱼MP的功效：1）证明我们可以在血管环境中降低病原性葡萄球菌定殖在鲨鱼表面上定植，并且2）证明我们可以在sharklet cornface surface上降低血小板粘合剂和随后的链血上的状态。然后，第二阶段的工作将专注于使用体内动物模型的验证，其他病原体的体外测试，针对有害药物化合物的耐用性测试以及鲨鱼CVC的制造方法。第一阶段和II的结果对于与我们已经讨论此应用程序的私营部门合作伙伴/投资者的III阶段合作至关重要。成功的多相SBIR的潜在影响将产生新的鲨鱼CVC，该鲨鱼CVC将使临床医生/医院通过大大减轻医院感染的重大负担和由于血栓形成导致的院内死亡率来改善患者护理并节省大量成本。 公共卫生相关性：中央静脉导管（CVC）最严重，最常见的并发症是导管相关的血液感染（CRBSI），占由于医院获得的感染而导致的死亡的30％以上，并造成医疗费用每年高达20亿美元的医疗费用，而在美国，以及与导管相关的血栓造成的疾病，这是一位促成势力的促销者，该疾病是促成Throns的促进性，该疾病是促成Throns th Throns of Thrombul th Throns of Thrombol，促成了促成势力，一位促进了促进疾病，一名促成势力，一名促进疾病，一家人的疾病造成死亡率。 Unlike impregnation of the CVC surface with antimicrobial agents or coating with anticoagulants that have severe limitations in addressing CRBSI and CRT, a next-generation solution that incorporates the non-kill Sharklet" microscopic pattern onto the catheter surface can inhibit both bacterial colonization that leads to CRBSI and platelet adhesion that leads to CRT, thereby improving patient care. This multi-phase research effort将有助于开发和商业化抗感染，抗栓性的CVC，该CVC在导管表面积分的鲨鱼微模式，目的是通过降低院内感染，发病率，死亡率和成本来改善患者的安全性。