Preventing Spinal Infection: Ultrasound Triggered Prophylaxis

 描述：尽管围手术期积极使用抗生素治疗，但在接受脊柱手术的患者中，每20人中就有1人发生感染。对于创伤性损伤患者，这些比率很容易超过10%。到2030年，每年有500万例手术，而感染治疗只有部分有效，感染造成的费用和残疾将继续增加。 坐骑。因此，预防感染的更有效手段是临床上的当务之急。为了达到最有效的效果，新的治疗方法必须在病原体附着在植入物表面降低抗生素和免疫敏感性之前根除病原体。意识到这一要求，我们的实验室长期以来一直专注于创建防止细菌定植的抗菌植入系统的新方法。我们的假设是，在围手术期内保持硬件部位的超治疗抗生素浓度将防止感染的建立，并降低感染率。为了测试这一点，我们建议开发一种简单的多孔聚醚醚酮(PEEK)鞘，它包裹在脊柱棒周围，并在应用超声波(US)时释放其内容物--毫克量的抗生素组合；所有抗生素 将在围手术期从鞘中释放，以确保积极的预防。抗生素组合的使用有望将抗药性病原体降至最低，并确保根除所有污染病原体。有三个具体目标1：表征美国激活的抗菌剂释放系统的稳定性和释放动力学。2：体外检测鞘对邻近五金件细菌定植的能力。3：在体内感染模型中确定鞘在根除感染中的作用。本申请中详细介绍的方法确保了在手术后立即根除病原体。这一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(植入物感染)和生物材料工程师(PEEK和植入物回收和分析)的努力。它直接解决脊柱植入物感染的问题，使用经过验证的材料的创新应用，这些材料在完成该项目后可以快速有效地转化为临床领域。我们预计，这种疗法将进一步降低感染率，并改善脊柱手术后与感染相关的疼痛、痛苦、残疾和死亡率。

 DESCRIPTION: Despite aggressive peri-operative antibiotic treatments, between 1 in 20 and 1 in 100 patients undergoing spinal surgery develop an infection. For patients with traumatic injury, these rates easily exceed 10%. With > 5 million annual surgeries by 2030 and only partially effective infection treatments, the cost and disability due to infection will continue to mount. More effective means to prevent infection are therefore a clinical imperative. To be most effective, new treatments must eradicate pathogens before their adherence to the implant surface attenuates antibiotic and immune susceptibility. Aware of this requirement, our laboratories have long focused on new ways to create antibacterial implant systems that prevent bacterial colonization. Our hypothesis is that maintaining supra-therapeutic antibiotic concentrations at the hardware site during the peri-operative period will prevent establishment of infection and lower infection rates. To test this, we propose to develop a simple porous polyether ether ketone (PEEK) sheath that surrounds the spinal rod and releases its contents--mg quantities of a combination of antibiotics--upon application of ultrasound (US); all antibiotics will be released from sheaths during the peri-operative period to ensure aggressive prophylaxis. Use of antibiotic combinations is expected to minimize antibiotic resistant pathogens and to ensure that all contaminating pathogens are eradicated. There are three specific aims 1: To characterize the stability and release kinetics of an US-activated antimicrobial release system. 2: To test the ability of the sheaths to prevent bacterial colonization of adjacent hardware in vitro. 3: To determine the utility of the sheath in eradicating infection in an in vivo model of infection. The approach detailed in this application ensures eradication of pathogens in the immediate post-operative period. The concept and impetus has arisen through the efforts of a spinal surgeon, US physicist, basic scientist (implant infections), and biomaterials engineer (PEEK and implant retrieval and analysis). It directly addresses the problem of spinal implant infections using innovative applications of proven materials that upon completion of this project can quickly and effectively be translated to the clinical arena. We anticipate that this therapy wil further lower infection rates and ameliorate the pain, suffering, disability, and mortality associated with infections that occur after spinal surgery.