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20,000多名患者被诊断出患有联合感染。尽管外科手术 干预坏死组织的清理术，具有杀菌溶液的侵略性灌洗和全身性 抗生素治疗，死亡率超过11％，复发很常见。此外，侵略性 治疗损害关节确保以后的关节炎。一旦细菌进入关节囊，我们的初步 数据表明，由于形成大的，细菌污染物成为抗生素治疗的顽固污染物 可能与组织浮动或松散相关的细菌聚集体。我们建议开发新的 破坏和防止败血性关节中细菌骨料重新形成的治疗方法允许有效 抗菌治疗。要攻击这个问题，我们提出了三个具体目标：特定目的1：抑制 通过用改变蛋白质聚集的药物治疗滑液中细菌聚集体的形成。我们 假设抑制聚集将允许抗生素获取并提高有效性。具体目标 2：使用超声介导的微泡破裂在离体中透化滑液聚集体 关节模型。我们假设微泡的空化将使聚集体渗透以增加 对结块内细菌的抗生素功效。特定目的3：消除体内关节感染， 通过合并的微泡/药物/抗生素处理。我们将检验关节感染的假设 可以在局部使用微气泡的局部应用在剂的情况下进行更有效的治疗 来自特定的目标1和amikacin。为了攻击这个问题，我们组建了一个骨科专家团队 感染，疾病动物模型，超声物理，肌肉骨骼疾病以及实践 骨科医生专门从事关节感染。我们提出的方法的成功将导致更高 治疗成功率，以使与关节感染相关的疼痛，成本，痛苦和死亡率将是 明显减少了。