Preventing Spinal Infection: Ultrasound Triggered Prophylaxis

预防脊柱感染：超声触发预防

• 批准号: 9898313
• 负责人: Flemming Forsberg
• 金额: $ 52.09万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9898313
• 关键词: Address; Adherence; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Area; Attenuated; Awareness; Bacteria; Biocompatible Materials; Clinical; Combined Antibiotics; Complication; Engineering; Ensure; Ethers; Evaluation; Free Will; Generations; Goals; Government; Histology; Hospitals; Immune; Immunohistochemistry; Implant; In Vitro; Infection; Infection prevention; Ketones; Kinetics; Laboratories; Longevity; Measures; Mechanics; Minimum Inhibitory Concentration measurement; Modeling; Monitor; Operative Surgical Procedures; Oryctolagus cuniculus; Pain; Patient Discharge; Patients; Perioperative; Persons; Porosity; Postoperative Period; Predisposition; Prophylactic treatment; Research; Resistance; Retrieval; Rod; Rupture; Sampling; Scientist; Site; Spinal; Spinal Fusion; Spine surgery; Surface; Surgeon; Surgical Wound Infection; System; Testing; Therapeutic; Thick; Time; Tissues; Toxic effect; Translating; Traumatic injury; Treatment Cost; Ultrasonography; Vancomycin; antimicrobial; bone; cost; design; disability; drug resistant pathogen; in vivo Model; infection rate; innovation; instrument; mortality; pathogen; prevent; prophylactic; public health relevance; seal; spine bone structure; substantia spongiosa

 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.

 描述：尽管在围手术期进行了积极的抗生素治疗，但对于遭受创伤的患者，仍有二十分之一至一百人中出现感染，到 2030 年，每年进行的手术数量将超过 500 万例，而这一比例很容易超过 10%。有效的感染治疗，感染造成的费用和残疾将继续 因此，为了最有效地预防感染，新的治疗方法必须在病原体附着在种植体表面削弱抗生素和免疫敏感性之前将其消灭，我们的实验室长期以来一直致力于寻找新的方法。创建防止细菌定植的抗菌植入系统。我们的假设是，在围手术期在硬件部位维持超治疗抗生素浓度将防止感染并降低感染率。建议开发一种简单的多孔聚醚醚酮 (PEEK) 护套，该护套在应用所有抗生素后包围脊柱杆及其内容物（毫克量的抗生素组合）； 将在围手术期从鞘中释放，以确保使用抗生素组合可最大程度地减少抗生素耐药性病原体，并确保根除所有污染病原体。有三个具体目标 1：表征稳定性和释放。美国激活的抗菌释放系统的动力学 2：测试护套在体外防止邻近硬件细菌定植的能力。在感染的体内模型中根除感染的方法确保在术后立即根除病原体这一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（植入物感染）的努力而提出的。 ）和生物材料工程师（PEEK 和植入物检索和分析），它使用经过验证的材料的创新应用直接解决脊柱植入物感染的问题，我们预计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。这种疗法将进一步降低感染率，并改善与脊柱手术后发生的感染相关的疼痛、痛苦、残疾和死亡率。

项目成果

Staphylococcus aureus Floating Biofilm Formation and Phenotype in Synovial Fluid Depends on Albumin, Fibrinogen, and Hyaluronic Acid.

• DOI: 10.3389/fmicb.2021.655873
• 发表时间: 2021
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Knott S;Curry D;Zhao N;Metgud P;Dastgheyb SS;Purtill C;Harwood M;Chen AF;Schaer TP;Otto M;Hickok NJ
• 通讯作者: Hickok NJ

Does annealing improve the interlayer adhesion and structural integrity of FFF 3D printed PEEK lumbar spinal cages?

• DOI: 10.1016/j.jmbbm.2019.103455
• 发表时间: 2020-02-01
• 期刊: JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
• 影响因子: 3.9
• 作者: Basgul, Cemile;Yu, Tony;Kurtz, Steven M.
• 通讯作者: Kurtz, Steven M.

3D printed porous PEEK created via fused filament fabrication for osteoconductive orthopaedic surfaces.

• DOI: 10.1016/j.jmbbm.2020.103850
• 发表时间: 2020-05
• 期刊: Journal of the mechanical behavior of biomedical materials
• 影响因子: 3.9
• 作者: H. Spece;T. Yu;Anthony Law;M. Marcolongo;Steven M. Kurtz

Bacterial toxins in musculoskeletal infections.

• DOI: 10.1002/jor.24683
• 发表时间: 2021-03
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Saeed K;Sendi P;Arnold WV;Bauer TW;Coraça-Huber DC;Chen AF;Choe H;Daiss JL;Ghert M;Hickok NJ;Nishitani K;Springer BD;Stoodley P;Sculco TP;Brause BD;Parvizi J;McLaren AC;Schwarz EM
• 通讯作者: Schwarz EM

Are Medical Grade Bioabsorbable Polymers a Viable Material for Fused Filament Fabrication?

• DOI: 10.1115/1.4043841
• 发表时间: 2019-07
• 期刊: Journal of medical devices
• 作者: J. Schachtner;M. Frohbergh;N. Hickok;S. Kurtz