Pathogenesis & epidemiology of S epidermidis ventricular assist device infections

描述（由申请人提供）：心室辅助装置（VADs）是晚期心力衰竭治疗的重要组成部分。他们维持病人直到心脏移植或恢复，也被批准为那些不符合移植条件的“目的地治疗”。由于供体心脏供不应求，vad有可能成为移植的常规替代品。然而，VADs的使用受到感染频率高的限制，感染发生在18-59%的病例中。vad相关感染难以诊断，由于缺乏普遍接受的诊断标准，这些感染的临床和流行病学评估受到限制。使用来自VAD受者的多中心前瞻性研究的数据，我们将制定VAD感染的诊断标准，我们的目标是验证其他研究者和临床医生的使用。关于表皮葡萄球菌的发病机制和分子流行病学的信息也很有限，表皮葡萄球菌是与这些感染相关的最常见病原体。它的突出作用可能是由于它作为皮肤和鼻子的殖民者无处不在，以及它在假体装置上粘附和形成生物膜的能力。我们将评估定植VAD患者的表皮葡萄球菌样本，以确定表皮葡萄球菌共生菌群在VAD相关感染的后续发展中的作用。我们将使用脉冲场凝胶电泳等技术确定菌株的抗生素敏感性并描述它们的遗传相关性。我们将解释这些因素是如何随时间变化的。我们还旨在确定导致特定表皮葡萄球菌菌株引起vad相关感染的能力的毒力决定因素。为了做到这一点，我们将使用微阵列分析来比较感染和共生分离物，以确定与感染相关的基因。这些潜在的毒力基因将在进一步的研究中进行研究。我们的发现可能有助于阐明潜在的疫苗或治疗靶点。这项研究对我作为一名传染病和流行病学教员的职业发展至关重要，我的专业是葡萄球菌分子流行病学和发病机制。相关性：心脏辅助装置经常被细菌感染，如表皮葡萄球菌。这些感染很难诊断，我们对它们如何以及为什么发生的了解有限。这项研究将改善对这些感染的诊断，并将确定导致这些感染的基因，以便开发疫苗和新的治疗方法。

DESCRIPTION (provided by applicant): Ventricular assist devices (VADs) are an important part of the treatment of advanced heart failure. They sustain patients until cardiac transplantation or recovery and are also approved as "destination therapy" for those ineligible for transplant. As donor hearts are in short supply, VADs have the potential to become a routine substitute for transplantation. However, the use of VADs is limited by the high frequency of infection, which occurs in 18-59% of cases. VAD-related infections are difficult to diagnose and the clinical and epidemiologic assessment of these infections is limited by the lack of universally accepted diagnostic criteria. Using data from a multi-center, prospective study of VAD recipients, we will develop diagnostic criteria for VAD infections that we aim to validate for use by other investigators and clinicians. There is also limited information on the pathogenesis and molecular epidemiology of Staphylococcus epidermidis, the most common pathogen associated with these infections. Its prominent role may be due to its ubiquitous presence as a skin and nares colonizer and its ability to adhere to and form biofilms on prosthetic devices. We will evaluate samples of S. epidermidis colonizing VAD patients to determine the role of S. epidermidis commensal flora in the subsequent development of VAD-related infection. We will determine strains' antibiotic susceptibility and describe their genetic relatedness using techniques such as pulsed-field gel electrophoresis. We will explain how these factors change over time. We also aim to identify virulence determinants that contribute to the ability of particular S. epidermidis strains to cause VAD-related infections. To do this, we will use microarray analyses to compare infection and commensal isolates in order to identify genes associated with infection. These potential virulence genes will be investigated in additional studies. Our findings may help elucidate potential vaccine or therapeutic targets. This research will be essential to my career development as a faculty in infectious diseases and epidemiology who specializes in Staphylococcal molecular epidemiology and pathogenesis. Relevance: Heart-assist devices are frequently infected with bacteria such as Staphylococcus epidermidis. These infections are difficult to diagnose and we have limited understanding of how and why they occur. This research will improve the diagnosis of these infections and will identify the genes responsible for them so that vaccines and new treatments can be developed.