Pathogenesis & epidemiology of S epidermidis ventricular assist device infections

发病

• 批准号: 7890442
• 负责人: Rachel J. Gordon
• 金额: $ 12.43万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7890442
• 关键词: Antibiotic Resistance; Antibiotic susceptibility; Antibiotics; Bacteria; Blood Cell Count; Characteristics; Clinical; Comorbidity; Data; Destinations; Development; Devices; Diagnosis; Diagnostic; Disease; Drainage procedure; Environment; Epidemiology; Exposure to; Faculty; Fever; Frequencies; Future; Genes; Genetic; Gram' s stain; Heart; Heart Transplantation; Heart failure; Heart-Assist Devices; Hospitals; Incidence; Individual; Infection; Infectious Disease Epidemiology; Laboratories; Microbial Biofilms; Molecular Epidemiology; Nose; Observational Study; Operative Surgical Procedures; Operon; Organism; Pathogenesis; Patients; Prospective Studies; Prosthesis; Pulsed-Field Gel Electrophoresis; Recovery; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Schedule; Severities; Site; Skin; Source; Specific qualifier value; Specimen; Staphylococcus epidermidis; System; Techniques; Time; Transplantation; Vaccines; Virulence; Virulence Factors; Virulent; career development; clinical Diagnosis; implantable device; implantation; improved; in vitro Model; novel vaccines; pathogen; programs; prophylactic; prospective; routine Bacterial stain; therapeutic target; ventricular assist device

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.

描述（由申请人提供）：心室辅助装置（VAD）是晚期心力衰竭治疗的重要组成部分。它们维持患者直到心脏移植或康复，并且还被批准为不适合移植的患者的“目的地治疗”。由于供体心脏供应短缺，VAD有可能成为移植的常规替代品。然而，VAD的使用受到感染频率高的限制，感染发生率为18-59%。VAD相关感染很难诊断，这些感染的临床和流行病学评估受到缺乏普遍接受的诊断标准的限制。使用来自VAD接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人员和临床医生的使用。关于表皮葡萄球菌（与这些感染相关的最常见病原体）的发病机制和分子流行病学的信息也很有限。其突出的作用可能是由于其作为皮肤和鼻孔定植者的普遍存在以及其粘附并在假体装置上形成生物膜的能力。我们将评估S的样品。表皮葡萄球菌定殖VAD患者，以确定S.在VAD相关感染的后续发展中表皮细胞植物群。我们将确定菌株的抗生素敏感性，并使用脉冲场凝胶电泳等技术描述它们的遗传相关性。我们将解释这些因素如何随时间变化。我们的目标也是确定毒力决定因素，有助于特定的S。表皮葡萄球菌菌株引起VAD相关感染。为了做到这一点，我们将使用微阵列分析来比较感染和分离株，以确定与感染相关的基因。这些潜在的毒力基因将在其他研究中进行研究。我们的发现可能有助于阐明潜在的疫苗或治疗靶点。这项研究将是必不可少的，我的职业发展作为一个教师在传染病和流行病学谁专门从事葡萄球菌分子流行病学和发病机制。相关性：心脏辅助装置经常感染细菌，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。