Diagnosis and Tracking of Spinal Staphylococcus aureus Orthopaedic Implant Infections

脊柱金黄色葡萄球菌骨科植入物感染的诊断和追踪

• 批准号: 10464246
• 负责人: Cheryl Lynne Ackert-Bicknell
• 金额: $ 20.71万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-24 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10464246
• 关键词: Anatomy; Antibiotic Therapy; Antibodies; Antibody titer measurement; Antibody-Producing Cells; Antigens; B-Cell Activation; Benchmarking; Biological Assay; Blood; Blood Circulation; Blood Tests; Blood specimen; Body Temperature; C-reactive protein; Cell Culture Techniques; Clinical; Complex; Complication; Cultured Cells; Data; Death Rate; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disadvantaged; Early Intervention; Environment; Erythrocyte Sedimentation Rate; Fever; Foot joint structure; Genus staphylococcus; Goals; Gold; Harvest; Immune response; Immunoassay; Immunoglobulin G; Immunoglobulin-Secreting Cells; Implant; In Vitro; Infection; Infectious Agent; Infectious Skin Diseases; Joint Prosthesis; Knee; Lead; Liquid substance; Masks; Measurement; Measures; Methods; Microbial Biofilms; Microbiology; Monitor; Morbidity - disease rate; Musculoskeletal; Neurologic Symptoms; Nomograms; Operative Surgical Procedures; Organism; Orthopedics; Outcome; Pain; Patients; Peripheral Blood Mononuclear Cell; Polymers; Postoperative Period; Practice Guidelines; Property; Rapid diagnostics; Sampling; Serum; Serum Markers; Site; Spinal; Staphylococcus aureus; Staphylococcus aureus infection; Surface; Surgical Wound Infection; Temperature; Testing; Therapeutic; Therapeutic Intervention; Time; Vertebral column; White Blood Cell Count procedure; Whole Blood; Work; antimicrobial; base; cost; cytokine; diagnostic accuracy; diagnostic tool; diagnostic value; experience; extracellular; foot; implant associated infection; implantation; in vivo; joint infection; novel; pathogen; prognostic; response; spine bone structure; standard of care; success; treatment guidelines; treatment response

Spinal infections are a serious complication of vertebral implantation surgery with a death rate as high as 20% in the first year. Challenging to identify, especially in the early stages, they are typically diagnosed after becoming well established when the patient is experiencing significant pain and permanent vertebral damage. Here, we propose to explore the early immune response to these infections, focusing on Staphylococcus aureus, (S. aureus), the most frequent and serious among the multiple pathogens that cause spinal implant infections. Our goal is to develop a new way to diagnose spinal implant infections that will: 1) be usable early in the infection's course, 2) cost less than current approaches, 3) require only a routine blood sample, and 4) be capable of monitoring therapeutic success. Most patients have high circulating levels of S. aureus-specific antibodies, and these levels increase with infection, but remain elevated long after the infection has been resolved. To provide a more sensitive diagnostic tool and at the same time create a simple measure for monitoring therapeutic success, we propose to measure the antibodies produced by circulating Antibody- Secreting Cells (ASC) that are present in the blood while the infection is ongoing and rapidly decline thereafter. ASC can be harvested from whole blood, washed free of serum antibodies, and cultured in vitro for a short time. These cultured cells will secrete newly synthesized antibodies, as well as the cytokines, yielding “medium enriched for newly synthesized antibodies” or MENSA, for short. Antibody titers of MENSA fluid against antigens for specific pathogens and the cytokines being secreted can be measured using a multiplex immunoassay. In this proposal, we hypothesize that the diagnosis and monitoring of treatment response due to spine related S. aureus infection is feasible utilizing pathogen-specific antibodies secreted by ASC, and that the antigenic signatures will be distinct compared to other musculoskeletal infections. To test this hypothesis, we will examine MENSA antibody and cytokine levels in patients with a known or suspected infection associated with previously placed spinal orthopedic implants. We will determine if MENSA antibodies alone or in combination with cytokines can discriminate between patients with S. aureus infections or infections due to other pathogens. Accuracy will be determined by comparing to the clinical gold standard of bacterial culture. We will also determine if we can use MENSA to track the response to treatment for S. aureus infection. This study is focused on S. aureus as we can diagnosis this pathogen via culture, giving us a benchmark for accuracy, even though 48% of the time, the infectious agent in spine infections cannot be determined by culture. This study is a proof-of-concept study that can be expanded to other pathogens that are complex to diagnose while also monitoring treatment when direct culture methods become impractical. The goal of this work is the creation of simple, inexpensive, rapid diagnostic method that can lead to earlier interventions and better outcomes for spinal infections patients.

脊柱感染是椎体植入手术的严重并发症，死亡率高达20%。 在第一年。具有挑战性的识别，特别是在早期阶段，通常是在 当患者经历严重的疼痛和永久性的脊椎损伤时，就会变得很好。 在这里，我们建议探索对这些感染的早期免疫反应，重点是葡萄球菌。 金黄色葡萄球菌(S.aureus)是导致脊柱植入物的多种病原体中最常见和最严重的 感染。我们的目标是开发一种诊断脊柱植入物感染的新方法：1)早期可用 感染的病程，2)比目前的方法花费更少，3)只需要常规的血液样本，以及4) 能够监测治疗的成功。大多数患者循环中的金黄色葡萄球菌水平较高。 抗体，这些水平随着感染而增加，但在感染后很长一段时间仍保持在较高水平 解决了。为了提供更灵敏的诊断工具，同时为 为了监测治疗的成功，我们建议测量循环抗体产生的抗体- 在感染期间血液中存在的分泌细胞(ASC)，并在感染后迅速下降。 ASC可以从全血中获取，洗去血清抗体，并在体外培养一段时间 时间到了。这些培养的细胞将分泌新合成的抗体和细胞因子，从而产生“介质”。 富含新合成的抗体“，简称门萨。门萨口服液的抗体效价 特定病原体的抗原和分泌的细胞因子可以用多重的方法来测量。 免疫分析。在这项建议中，我们假设诊断和监测由于以下原因引起的治疗反应 利用ASC分泌的病原体特异性抗体感染脊柱相关金黄色葡萄球菌是可行的，并且 与其他肌肉骨骼感染相比，抗原特征将是不同的。为了检验这一假设， 我们将检测已知或疑似感染患者的Mensa抗体和细胞因子水平。 与先前放置的脊柱矫形植入物相关。我们将确定门萨抗体是单独还是 结合细胞因子可以区分金黄色葡萄球菌感染或因 其他病原体。准确性将通过与临床细菌培养的黄金标准进行比较来确定。 我们还将确定是否可以使用Mensa来跟踪金黄色葡萄球菌感染治疗的反应。这 研究的重点是金黄色葡萄球菌，因为我们可以通过培养诊断这种病原体，为我们提供了一个基准 准确性，即使在48%的时间里，脊柱感染的感染源不能通过 文化。这项研究是一项概念验证性研究，可以扩展到其他复杂的病原体 当直接培养方法变得不可行时，在诊断的同时还监测治疗。这样做的目的是 工作是创造简单、廉价、快速的诊断方法，可以导致更早的干预和 改善脊椎感染患者的预后。