Synovial Fluid and Joint Sepsis

滑液和关节败血症

• 批准号: 10183167
• 负责人: Noreen J Hickok
• 金额: $ 44.1万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10183167
• 关键词: Acute suppurative arthritis due to bacteria; Amikacin; Animal Disease Models; Anti-Bacterial Agents; Antibiotic Therapy; Antibiotics; Arthritis; Bacteria; Biochemical; Characteristics; Clinical; Coagulation Process; Data; Debridement; Diagnosis; Effectiveness; Ensure; Excision; Exhibits; Family suidae; Fibrin; Human; In Situ; In Vitro; Infection; Irrigation; Joint Capsule; Joints; Local Anti-Infective Agents; Mediating; Metabolic; Methicillin; Microbial Biofilms; Microbiology; Microbubbles; Microscopic; Modeling; Musculoskeletal Diseases; Operative Surgical Procedures; Orthopedics; Pain; Patients; Permeability; Pharmaceutical Preparations; Physics; Prevention; Protease Inhibitor; Proteins; Recurrence; Rupture; Staphylococcus aureus; Staphylococcus epidermidis; Structure; Surface; Surgeon; Synovial Fluid; Synovial joint; Testing; Tissues; Treatment Efficacy; Ultrasonography; aggressive therapy; antimicrobial; barrier to care; base; combat; cost; crosslink; effective therapy; in vivo; joint destruction; joint infection; joint injury; methicillin resistant Staphylococcus aureus; mortality; necrotic tissue; neutrophil; novel therapeutics; porcine model; prevent; protein aggregation; septic; success

ABSTRACT In 2013, more than 20,000 patients in the US were diagnosed with joint infection. Despite surgical intervention with debridement of necrotic tissue, aggressive lavage with antiseptic solutions, and systemic antibiotic treatment, the mortality rate exceeds 11% and recurrence is common. Furthermore, the aggressive treatments damage the joint ensuring later arthritis. Once bacteria access the joint capsule, our preliminary data suggest that bacterial contaminants become recalcitrant to antibiotic treatments due to formation of large bacterial aggregates that can be floating or loosely associated with tissues. We propose to develop new treatments that disrupt and prevent re-formation of bacterial aggregates in septic joints to allow effective antibacterial treatment. To attack this problem, we propose three specific aims: Specific Aim 1: To inhibit bacterial aggregate formation in synovial fluid through treatment with drugs that alter protein aggregation. We hypothesize that inhibition of aggregation will allow antibiotic access and increased effectiveness. Specific Aim 2: To permeabilize synovial fluid aggregates using ultrasound-mediated microbubble rupture in an ex vivo model of the joint. We hypothesize that microbubble cavitation will permeabilize aggregates to increase antibiotic efficacy towards bacteria within the clump. Specific Aim 3: To eradicate joint infection, in vivo, through combined microbubble/drug/antibiotic treatments. We will test the hypothesis that joint infections may be treated more effectively by the local application of microbubble cavitation in the presence of agents from Specific Aim 1 and amikacin. To attack this problem, we have assembled a team of experts in orthopaedic infection, animal models of disease, ultrasound physics, musculoskeletal disease together with a practicing orthopaedic surgeon specializing in joint infection. The success of our proposed approach will lead to higher treatment success rates, so that the pain, cost, suffering and mortality associated with joint infections will be markedly reduced.

摘要 2013年，美国有超过20，000名患者被诊断患有关节感染。尽管进行了手术 通过坏死组织清创术、用防腐剂溶液积极灌洗和全身性 抗生素治疗，死亡率超过11%，复发是常见的。此外，侵略性 治疗会损害关节，从而导致关节炎。一旦细菌进入关节囊， 数据表明细菌污染物由于形成大的 细菌聚集体可以漂浮或松散地与组织结合。我们建议开发新的 破坏和防止脓毒症关节中细菌聚集体的重新形成以允许有效的 抗菌处理为了解决这个问题，我们提出了三个具体目标：具体目标1： 通过使用改变蛋白质聚集的药物治疗，滑液中的细菌聚集体形成。我们 假设聚集抑制将允许抗生素进入并增加有效性。具体目标 2：使用超声介导的微泡破裂在体外透化滑液聚集体 关节的模型。我们假设微泡空化将渗透聚集体，以增加 对菌丛内的细菌的抗生素效力。具体目标3：在体内根除关节感染， 通过微泡/药物/抗生素联合治疗。我们将检验关节感染 可以通过在试剂存在下局部应用微泡空化来更有效地治疗 特效药1和阿米卡星为了解决这个问题，我们召集了一个骨科专家小组， 感染，疾病的动物模型，超声物理学，肌肉骨骼疾病连同实践 专攻关节感染的整形外科医生。我们提出的方法的成功将导致更高的 治疗成功率，因此，与关节感染相关的疼痛，费用，痛苦和死亡率将 明显减少。

项目成果

A Platelet-Rich Plasma-Derived Biologic Clears Staphylococcus aureus Biofilms While Mitigating Cartilage Degeneration and Joint Inflammation in a Clinically Relevant Large Animal Infectious Arthritis Model.

• DOI: 10.3389/fcimb.2022.895022
• 发表时间: 2022
• 期刊: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
• 影响因子: 5.7
• 作者: Gilbertie, Jessica M.;Schaer, Thomas P.;Engiles, Julie B.;Seiler, Gabriela S.;Deddens, Bennett L.;Schubert, Alicia G.;Jacob, Megan E.;Stefanovski, Darko;Ruthel, Gordon;Hickok, Noreen J.;Stowe, Devorah M.;Frink, Alexa;Schnabel, Lauren V.
• 通讯作者: Schnabel, Lauren V.