Pathogen-specific and Prognosis of S. aureus infection in Orthopaedic Surgery

摘要 金黄色葡萄球菌是假体周围关节感染(50%)和糖尿病足溃疡(DFU)的主要病原体。 (46-68%)。大多数感染的足部溃疡患者最初都会寻求足部保全治疗，这是一种策略 这包括清创，然后进行为期6周的静脉抗生素治疗。有了这个 一些患者会保留双脚，而另一些患者将面临更高的进一步扩散风险。 感染的可能性。目前，还没有灵敏和特异的诊断工具来监测病原体的 持续感染，并提供足部抢救工作成功的预后衡量标准。成功 这种诊断工具的开发将对临床医生决定保留或截肢 脚的感染部位。宿主体液免疫反应可以通过检测病原体- 由血清或抗体分泌细胞(ASC)产生的特定新合成抗体(NSA) 只有在活动性感染时才会进入血液。我们建立了一种新的金黄色葡萄球菌ASC检测方法 应用该免疫分析方法诊断和监测足部金黄色葡萄球菌的感染性。 溃疡。我们推测，血液样本中NSA的变化为监测提供了有用的指标 金黄色葡萄球菌的致病性以表征治疗反应，并及早发现初始治疗 失败，这可能会导致反复感染。这些信息将使我们能够准确地监控 抗生素治疗的疗效，并及时作出手术决定。因此，后续研究是 有理由对以下假设进行检验：1)ASC检测可作为S。 感染足部溃疡初期的金黄色葡萄球菌感染和2)ASC检测提供了 衡量治疗反应和临床结果的预后。为了测试这一点，我们提出了两个具体的 目标。在目标1中，我们将测量免疫分析诊断金黄色葡萄球菌的敏感性和特异性。 单一微生物(仅限金黄色葡萄球菌)和多微生物(金黄色葡萄球菌和一种或多种)患者的感染 其他细菌)感染足部溃疡。有足部溃疡临床症状和体征的患者 感染将从PI的临床实践中招募，血液样本将进行S。 金黄色葡萄球菌特异性抗体。在目标2中，我们将评估免疫分析有效监测 金黄色葡萄球菌的致病性用于表征治疗反应和预测临床结果。我们会 在4周、8周和12周采集血样，以调查临床表现的愈合与不愈合 溃疡愈合与NSA的变化相关。我们还将调查升高的NSA水平是否会对S。 金黄色葡萄球菌在8周(抗生素疗程结束6周后2周)可预测持续性 或反复感染。新的免疫分析可作为一种重要的诊断和预后 监测足部溃疡金黄色葡萄球菌感染的工具。拟议的研究需要正式 证实这些针对感染足部溃疡患者的新干预措施的初步观察。

Abstract S. aureus is the major pathogens in periprosthetic joint infection (>50%) and diabetic foot ulcers (DFU) (46- 68%). Most infected foot ulcer patients undertake initial pursuit of foot salvage therapy, a strategy that features debridement followed by 6 weeks long intravenous antibiotic treatment. With this approach, some patients will retain their feet while others will be placed at higher risk of further spread of infection. Currently, there is no sensitive and specific diagnostic tool for monitoring a pathogen’s ongoing infection and providing prognostic measure of success in foot salvage effort. Successful development of such diagnostic tool will critically aid the clinician’s decision to preserve or amputate the infected part of the foot. The host humoral immune response can be assessed by measuring pathogen- specific newly synthesized antibodies (NSA) produced by serum or antibody secreting cells (ASC) that emerge into blood only during active infection. We have developed novel ASC assay for S. aureus infection and have applied this immunoassay to diagnose and monitor the infectivity of S. aureus in foot ulcer. We postulate that the changes of NSA in the blood samples provides useful metrics in monitoring pathogenicity of S. aureus to characterize treatment responses, and early detection of initial treatment failure, which may lead to recurrent infection. These information will enable us to accurately monitor the efficacy of antibiotics treatment and to make timely surgical decision. Therefore, follow up studies are warranted to test the hypotheses that: 1) the ASC assay could serve as a reliable diagnostic tool for S. aureus infection at the initial presentation of infected foot ulcer and 2) the ASC assay provides a measure of treatment response and prognosis of clinical outcome. To test this, we propose two specific aims. In Aim 1, we will measure the sensitivity and specificity of immunoassay to diagnose S. aureus infection in patients with monomicrobial (S. aureus only) and polymicrobial (S. aureus and one or more other bacterial species) infected foot ulcer. Patients with clinical symptoms and signs of foot ulcer infection will be recruited from the PI’s clinical practice and blood samples will be processed for S. aureus specific antibodies. In Aim 2, we will assess the ability of immunoassay to effectively monitor pathogenicity of S. aureus to characterize treatment response and predict clinical outcome. We will obtain blood samples at 4, 8, and 12-weeks to investigate if clinical presentation of healing versus non- healing ulcers correlates with changes of NSA. We will also investigate if elevated NSA level against S. aureus at 8 weeks (2 weeks after completion of 6 weeks course of antibiotics) can predict a persistent or recurrent infection. The novel immunoassay may serve as an important diagnostic and prognostic tools for monitoring S. aureus infection in foot ulcer. The proposed research is needed to formally confirm these initial observations towards novel interventions for infected foot ulcer patients.