Synovial Fluid and Joint Sepsis

滑液和关节败血症

• 批准号: 9402991
• 负责人: Noreen J Hickok
• 金额: $ 54.05万
• 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 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9402991
• 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; Methicillin Resistance; Microbial Biofilms; Microbiology; Microbubbles; Microscopic; Modeling; Musculoskeletal Diseases; Necrosis; Operative Surgical Procedures; Orthopedics; Pain; Patients; Permeability; Pharmaceutical Preparations; Physics; Prevention; Protease Inhibitor; Proteins; Recurrence; Rupture; Sepsis; Staphylococcus aureus; Staphylococcus epidermidis; Surface; Surgeon; Synovial Fluid; Synovial joint; Testing; Tissues; Treatment Efficacy; Ultrasonography; antimicrobial; base; combat; cost; crosslink; effective therapy; in vivo; joint destruction; joint infection; joint injury; mortality; neutrophil; novel therapeutics; 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.

抽象的 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 清除坏死组织、用消毒液积极灌洗以及全身治疗等干预措施 抗生素治疗，死亡率超过11%，且复发常见。此外，攻击性的 治疗会损害关节，导致后来出现关节炎。一旦细菌进入关节囊，我们初步 数据表明，由于形成大的细菌污染物，细菌污染物对抗生素治疗变得难以抵抗。 可以漂浮或与组织松散结合的细菌聚集体。我们建议开发新的 破坏和防止化脓性关节中细菌聚集体重新形成的治疗方法，以实现有效的治疗 抗菌治疗。为了解决这个问题，我们提出了三个具体目标： 具体目标 1：抑制 通过改变蛋白质聚集的药物治疗，滑液中细菌聚集体形成。我们 假设抑制聚集将允许抗生素使用并提高有效性。具体目标 2：在体外使用超声介导的微泡破裂来透化滑液聚集体 关节模型。我们假设微泡空化将使聚集体渗透性增加 抗生素对菌群内细菌的功效。具体目标 3：消除体内关节感染， 通过微泡/药物/抗生素联合治疗。我们将检验关节感染的假设 在有药剂存在的情况下局部应用微泡空化可以更有效地治疗 来自特定目标 1 和阿米卡星。为了解决这个问题，我们组建了骨科专家团队 感染、疾病动物模型、超声物理、肌肉骨骼疾病以及实践 专门研究关节感染的骨科医生。我们提出的方法的成功将带来更高的 治疗成功率，从而使与关节感染相关的疼痛、费用、痛苦和死亡率将降低 明显减少。