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；作为美国十大死亡原因，它们对医学界提出了重大挑战。其中近一半的感染与医疗设备的使用有关。中心静脉导管 (CVC) 约占所有导管相关血流感染 (CRBSI) 的 90%。仅在美国，每年就有 300,000 例感染病例导致多达 28,000 人死亡。 CRBSI 会延长住院时间，造成人类痛苦，并增加医疗费用（高达 26.8 亿美元）。患有导管相关血栓 (CRT) 的患者发生感染的可能性是其他患者的四倍，高达 67% 的 CVC 患者会发生 CRT。除了增加感染风险外，CRT 还与血栓栓塞性疾病相关，而血栓栓塞性疾病是美国院内死亡的主要原因。目前预防 CRBSI 和 CRT 的范例是引入抗菌剂或抗血栓药物以降低细菌浓度或导管表面的血小板。抗菌导管的活性可能会被高浓度的细菌所淹没，其功效主要限于最初几天内药物的初始洗脱峰值。涂有抗凝剂的导管可能会出现污染问题，并且尚未被证明可以降低与血栓事件相关的死亡率。 Sharklet Technologies Inc. (STI) 旨在证明将我们专有的 Sharklet 微图案 (Sharklet MP) 集成到导管表面以最终减少 CVC 相关感染的可行性，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 可以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。这个多阶段 SBIR 项目的总体目标是开发、验证 Sharklet MP 表面在下一代抗感染、抗血栓 CVC 上的应用并将其商业化。第一阶段的具体目标是通过追求以下目标来展示 Sharklet MP 的功效：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）证明我们可以减少血小板粘附和随后的与无图案对照表面相比，Sharklet 表面上凝血酶的形成。第二阶段工作将集中于体内动物模型的验证、其他病原体的体外测试、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与私营部门合作伙伴/投资者的第三阶段合作至关重要，我们已经与他们讨论了该应用。成功的多阶段 SBIR 的潜在影响将是生产新的 Sharklet CVC，它将使临床医生/医院能够改善患者护理，并通过大幅减少医院感染和院内死亡率的主要负担，从而显着节省成本。血栓形成。 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)，该感染占医院获得性感染死亡人数的 30% 以上，且医疗费用高达仅在美国每年就花费 20 亿美元，而导管相关血栓形成 (CRT) 可能导致血栓栓塞，而血栓栓塞是导致院内死亡的主要原因。与用抗菌剂浸渍 CVC 表面或涂上抗凝剂在解决 CRBSI 和 CRT 方面具有严重局限性不同，下一代解决方案将非杀灭 Sharklet 微观图案结合到导管表面上，可以抑制细菌定植，从而导致CRBSI 和血小板粘附导致 CRT，从而改善患者护理。这项多阶段研究工作将有助于开发具有 Sharklet 微图案的抗感染、抗血栓 CVC 并将其商业化。集成在导管表面，旨在通过减少院内感染、发病率、死亡率和成本来提高患者安全。