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

项目摘要/摘要 脊柱融合术后的细菌感染是一个主要的临床问题，有1-10%的患者发生。 尽管围手术期接受积极的抗生素治疗，但仍有感染。每年超过500万例脊柱手术 预计到2030年。在抗生素治疗只有部分有效的情况下，成本(每名患者3.3万美元-11.4万美元) 2013年)，残疾感染负担将继续上升。预防感染的更有效手段是要付出代价的 和临床上的当务之急。新的治疗方法必须在病原体附着在脊柱上之前将其根除 在预防感染方面最有效的硬件。基于我们实验室以前的工作开发 抗菌植入系统，我们的假设是保持预防性药物的超治疗浓度 脊柱融合术后硬件部位的抗生素将降低术后感染率。为了测试 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，它可以夹住 放在脊柱棒上，并使用超声波(US)释放一组预防性抗生素，这些抗生素被加载到 在船内。联合使用抗生素有望降低抗生素耐药性的风险。 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的 从手术现场被根除了。该系统将允许抗生素的快速和完全释放 治疗水平，以根除手术硬件周围的污染细菌。一共有三个 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：评估美国触发的系统预防细菌的能力 在体外条件下相邻脊柱支架的定植，以及3：确定其预防作用 美国触发的根除细菌和预防邻近脊柱硬件感染的系统 在活体模型中。在整个拟议的项目中，申请者将接受每个领域的培训和支持 在适当的情况下执行研究任务，获得宝贵的技能和经验以帮助她晋升 独立研究人员的职业生涯。本提案中详细说明的方法，以及概念和 动力来自于脊柱外科医生、美国物理学家、基础科学家、 生物材料工程师、生物医学工程师。它解决了脊柱手术后的临床问题。 使用经过验证的材料的创新应用程序进行感染，并可以快速有效地转换为 项目竣工后的临床区。我们预计该项目将导致一种辅助治疗。 能够降低脊柱融合患者的感染率，有效地减少疼痛、残疾和死亡率 与脊柱融合术后感染有关。

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.