Ultrasound-Triggered Prophylaxis as a Novel Paradigm for Preventing Spinal Infection

超声触发预防作为预防脊柱感染的新范例

• 批准号: 9468875
• 负责人: Lauren Jo Delaney
• 金额: $ 5.9万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9468875
• 关键词: Address; Adherence; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Area; Bacteria; Bacterial Infections; Biocompatible Materials; Biomedical Engineering; Clinical; Clip; Combined Antibiotics; Complication; Engineering; Ensure; Ethers; Exposure to; Frequencies; Goals; Histology; Hour; Image; Immunohistochemistry; Implant; In Vitro; Infection; Infection prevention; Ketones; Kinetics; Laboratories; Longevity; Mechanics; Membrane; Methods; Modality; Modeling; Monitor; Operative Surgical Procedures; Oryctolagus cuniculus; Output; Pain; Patients; Perioperative; Pharmaceutical Preparations; Physiologic pulse; Porosity; Postoperative Period; Preventive measure; Prophylactic treatment; Recovery; Research; Research Personnel; Risk; Sampling; Scientist; Site; Spinal; Spinal Fusion; Spine surgery; Surface; Surgeon; System; Testing; Therapeutic; Thick; Time; Tissues; Toxic effect; Training Support; Transducers; Translating; Treatment Cost; Ultrasonography; Work; antimicrobial; antimicrobial drug; base; bone; career; combat; cost; design; disability; disability burden; exhaust; experience; in vivo Model; innovation; mortality; novel; pain reduction; pathogen; poly(lactic acid); prevent; prophylactic; response; retinal rods; skills

Project Summary/Abstract Bacterial infection following spinal fusion surgery is a major clinical concern, with 1-10% of patients developing infection despite aggressive peri-operative antibiotic treatments. Upwards of 5 million annual spinal surgeries are predicted by 2030. With only partially effective antibiotic treatments, the cost ($33k-$114k per patient in 2013) and disability burden of infection will continue to rise. More effective means to prevent infection are a cost and clinical imperative. New treatment modalities must eradicate pathogens prior to their adherence to the spinal hardware to be most effective in preventing infection. Based on previous work in our laboratories developing antibacterial implant systems, our hypothesis is that maintaining supra-therapeutic concentrations of prophylactic antibiotics at the hardware site following spinal fusion surgery will lower postoperative infection rates. To test this, we will develop a porous polyether ether ketone (PEEK) vessel coated with polylactic acid (PLA) that clips onto the spinal rod and uses ultrasound (US) to release a combination of prophylactic antibiotics that are loaded within the vessel. Use of a combination of antibiotics is expected to reduce the risk of antibiotic resistant pathogens while also ensuring that all contaminating pathogens, both gram-positive and gram-negative, are eradicated from the surgical site. This system will allow rapid and complete release of antibiotics at supra- therapeutic levels to eradicate contaminating bacteria surrounding the surgical hardware. There are three specific aims: 1: To characterize the release kinetics and stability of the US-triggered prophylactic release system using optimized ultrasound parameters, 2: To assess the ability of the US-triggered system to prevent bacterial colonization of adjacent spinal hardware under in vitro conditions, and 3: To determine the prophylactic utility of the US-triggered system in eradicating bacteria and preventing infection surrounding adjacent spinal hardware in an in vivo model. Throughout this proposed project, the applicant will receive training and support in each area as appropriate to perform the research tasks, gaining invaluable skills and experiences to help advance her career as an independent researcher. The approach detailed in this proposal, as well as the concept and impetus, has arisen through the collaborative efforts of a spinal surgeon, US physicist, basic scientist, biomaterials engineer, and biomedical engineer. It addresses the clinical problem of postoperative spinal infections using innovative applications of proven materials, and can quickly and effectively be translated to the clinical area upon completion of the project. We anticipate that the project will result in an adjunctive therapy capable of lowering infection rates in spinal fusion patients, effectively reducing the pain, disability, and mortality associated with postoperative infection following spinal fusion surgery.

项目概要/摘要 脊柱融合手术后的细菌感染是一个主要的临床问题，1-10% 的患者会出现细菌感染 尽管进行了积极的围手术期抗生素治疗，但仍有感染。每年脊柱手术超过 500 万例 预计到 2030 年。如果抗生素治疗仅部分有效，则每位患者的成本（33,000 美元至 114,000 美元） 2013）和感染致残负担将继续上升。更有效的预防感染手段是有代价的 和临床迫切需要。新的治疗方式必须在病原体粘附到脊柱之前将其消灭 硬件能够最有效地预防感染。基于我们实验室之前开发的工作 对于抗菌植入系统，我们的假设是维持预防性药物的超治疗浓度 脊柱融合手术后在硬件部位使用抗生素将降低术后感染率。测试 为此，我们将开发一种涂有聚乳酸 (PLA) 的多孔聚醚醚酮 (PEEK) 容器，可夹住 到脊柱杆上，并使用超声波（美国）释放装载的预防性抗生素组合 在容器内。联合使用抗生素有望降低抗生素耐药性的风险 病原体，同时还确保所有污染病原体，包括革兰氏阳性和革兰氏阴性 从手术部位根除。该系统将允许抗生素在超 治疗水平，以根除手术硬件周围的污染细菌。有三个 具体目标： 1：表征美国触发的预防性释放系统的释放动力学和稳定性 使用优化的超声参数，2：评估超声触发系统预防细菌的能力 体外条件下邻近脊柱硬件的定植，以及 3：确定预防效用 美国触发的系统可以消灭细菌并预防邻近脊柱硬件周围的感染 在体内模型中。在整个拟议项目中，申请人将获得各个领域的培训和支持 适当地执行研究任务，获得宝贵的技能和经验来帮助她进步 作为一名独立研究员的职业生涯。本提案中详细介绍的方法以及概念和 推动力，是通过脊柱外科医生、美国物理学家、基础科学家的共同努力而产生的， 生物材料工程师和生物医学工程师。它解决了术后脊柱的临床问题 使用经过验证的材料的创新应用来感染，并且可以快速有效地转化为 项目完成后的临床领域。我们预计该项目将产生辅助治疗 能够降低脊柱融合患者的感染率，有效减少疼痛、残疾和死亡率 与脊柱融合手术后的术后感染有关。