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（由申请人提供）：医疗保健获得性感染的发生率和严重程度正在增加;作为美国十大主要死亡原因，它们对医学界提出了重大挑战。这些感染中有近一半与医疗器械的使用有关。中心静脉导管（CVC）是约90%的导管相关性血流感染（CRBSI）的原因。仅在美国，每年就有多达28，000人因感染而死亡。CRBSI延长了住院时间，引发了人类痛苦，并扩大了医疗成本（高达26.8亿美元）。导管相关性血栓形成（CRT）患者发生感染的可能性高出4倍，高达67%的CVC患者发生CRT。除了增加感染风险外，CRT还与血栓栓塞性疾病相关，血栓栓塞性疾病是美国住院死亡的主要原因。目前预防CRBSI和CRT的范例是引入抗菌剂或抗血栓剂，以降低导管表面的细菌或血小板浓度。抗微生物导管的活性可能被高浓度的细菌压倒，并且它们的功效主要限于最初几天内的试剂的初始洗脱峰值。抗凝剂涂层导管可能会受到污染问题的困扰，并且尚未显示出降低与血栓形成事件相关的死亡率。Sharklet Technologies Inc. (STI)旨在证明将我们专有的Sharklet微图案（Sharklet MP）整合到导管表面的可行性，以最终减少CVC相关感染，并验证Sharklet表面防止血小板粘附导致血栓形成的能力。STI的初步数据表明，Sharklet MP抑制细菌定植以及血小板粘附和激活，从而提供预防CRBSI和CRT的双重能力。该多阶段SBIR项目的总体目标是开发、验证和商业化Sharklet MP表面在下一代抗感染、抗血栓CVC上的应用。具体的I期目标是通过追求以下目标来显示Sharklet MP的有效性：1）证明我们可以延缓血管环境中Sharklet表面上的致病性葡萄球菌定植，2）证明与未图案化的对照表面相比，我们可以减少Sharklet表面上的血小板粘附和随后的凝血酶形成。然后，第二阶段工作将重点关注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久性测试以及Sharklet CVC的制造方法。第一阶段和第二阶段的结果对于第三阶段与私营部门合作伙伴/投资者的合作至关重要，我们已经与他们讨论了这一应用。成功的多阶段SBIR的潜在影响将是生产一种新的Sharklet CVC，这将使临床医生/医院能够改善患者护理，并通过大幅减少医院感染的主要负担和血栓形成导致的住院死亡率来节省大量成本。 公共卫生相关性：中心静脉导管（CVC）最严重和最常见的并发症是导管相关血流感染（CRBSI）和导管相关血栓形成（CRT），CRBSI占医院获得性感染导致的死亡的30%以上，仅在美国每年的医疗费用就高达20亿美元，CRT可导致血栓栓塞，这是院内死亡率的主要原因。与在解决CRBSI和CRT方面具有严重局限性的用抗菌剂浸渍CVC表面或用抗凝剂涂覆不同，将非杀死Sharklet”微观图案结合到导管表面上的下一代解决方案可以抑制导致CRBSI的细菌定植和导致CRT的血小板粘附，从而改善患者护理。这项多阶段研究工作将有助于开发和商业化抗感染、抗血栓形成的CVC，其具有整合在导管表面上的Sharklet微图案，目的是通过减少院内感染、发病率、死亡率和成本来提高患者安全性。