Epidemiological and Genomic Characteristics of the Widely Disseminated C. difficile Strain, REA Group Y

广泛传播的艰难梭菌菌株 REA Y 组的流行病学和基因组特征

• 批准号: 10480500
• 负责人: Andrew Michael Skinner
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2027-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10480500
• 关键词: Accounting; Address; Anaerobic Bacteria; Antibiotics; Centers for Disease Control and Prevention (U.S.); Cephalosporins; Cessation of life; Characteristics; Classification; Clinical; Clostridium difficile; Communities; DNA Restriction Enzymes; Data; Epidemic; Epidemiologic Factors; Epidemiology; Evolution; Foundations; Genomics; Goals; Healthcare; Hospitals; Infection; K-Series Research Career Programs; Laboratories; Molecular; Molecular Analysis; Molecular Epidemiology; Morbidity - disease rate; Nature; Pathogenesis; Pathologic; Patients; Phylogenetic Analysis; Polymerase Chain Reaction; Population; Prevalence; Public Health; Recording of previous events; Reproduction spores; Resistance; Ribotypes; Risk; Risk Factors; Scientist; Site; Source; Surveys; Testing; Time; Training; United States; United States Department of Veterans Affairs; Vertebral column; Veterans; Virulence Factors; antimicrobial; bacterial genome sequencing; genome sequencing; healthcare-associated infections; innovation; military veteran; national surveillance; programs; protocol development; stool sample; surveillance data; surveillance study; trend; virtual; whole genome

Clostridioides difficile is a gram-positive, spore forming, anaerobic bacteria that is the cause of the most common healthcare associated infection. C. difficile infections (CDI) are estimated to cause nearly 450,000 infections and 30,000 deaths within the United States per year. Since the early 2000s, the epidemic strain identified as restriction endonuclease analysis (REA) group BI, PCR ribotype (RT) 027 (BI/RT027) has been the most common cause of CDI in the United States. However, in the past 10 years there has been a drastic change in the molecular epidemiology of C. difficile as BI/RT027 prevalence has decreased. Furthermore, there is evidence that healthcare-associated CDI (HA-CDI) is on the decline and community-associated CDI (CA-CDI) is increasing. One strain identified as REA group Y, which commonly correlates to RT 014 and 020 [Y(RT014/020)], has been endemic in the United States accounting for >5% of all CDI since the 1980s. As BI/RT027 associated CDI has decreased over the past 10 years, Y(RT014/020) related CDI have steadily increased and now account for 10-15% of all CDI. With the rise in CA-CDI, there is rising evidence that Y(RT014/020) resides within an unknown community reservoir. Despite a decades long prevalence and increasing concern with CA-CDI, a detailed molecular analysis of Y(RT014/020) has never been completed. Therefore, our proposal will be to complete a detailed molecular and clinical analysis in conjunction with a rigorous genomic analysis of Y(RT014/020) and BI/RT027 to assess the factors which contribute towards our overarching hypothesis that Y(RT014/020) resides within an unknown community reservoir. Support from the career development award (CDA) will provide Dr. Skinner with the necessary foundation and training to establish himself as a successful VA biomedical and laboratory clinician-scientist focused on the pathogenesis and epidemiology of C. difficile. The molecular epidemiology of C. difficile has continually shifted over multiple decades. These shifts are the results of underlying pathologic factors which influence strain selection. This innovative project will utilize C. difficile from multiple decades to understand the factors which have allowed for one strain (REA group Y) to remain endemic for decades. This information could be further utilized to understand which factors (i.e., antibiotic exposure) place Veterans at risk for developing a CDI and provide a deeper understanding into the mechanisms by which C. difficile is resistant to particular antibiotics. Therefore, the completion of this CDA will provide a critical foundation for Dr. Skinner and results from this project will be used to support Dr. Skinner's VA Merit Review application to study the mechanism by which C. difficile is resistant to certain cephalosporin antimicrobials.

梭状芽胞杆菌艰难梭菌是一种革兰氏阳性，孢子形成，厌氧细菌，是 最常见的医疗保健相关感染的原因。艰难梭菌感染（CDI）是 估计每年在美国导致近450,000次感染和30,000例死亡。 自2000年代初以来，流行病被确定为限制性核酸内切酶分析（REA） BI组，PCR核糖型（RT）027（BI/RT027）一直是CDI的最常见原因 美国。但是，在过去的十年中，分子发生了巨大变化 艰难梭菌的流行病学作为BI/RT027患病率下降。此外，还有 医疗保健相关CDI（HA-CDI）的证据正在下降，与社区相关 CDI（CA-CDI）正在增加。一个被识别为REA组的菌株，通常与 RT 014和020 [Y（RT014/020）]，在美国流行，占5％的5％ 自1980年代以来所有CDI。由于BI/RT027相关的CDI在过去10年中有所下降，因此 Y（RT014/020）相关的CDI稳步增加，现在占所有CDI的10-15％。和 CA-CDI的上升，有越来越多的证据表明Y（RT014/020）位于未知 社区水库。尽管长期患病率和对CA-CDI的关注越来越多，但 Y（RT014/020）的详细分子分析从未完成。因此，我们的建议 将与严格的结合完成详细的分子和临床分析 Y（RT014/020）和BI/RT027的基因组分析，以评估有助于的因素 我们认为Y（RT014/020）的总体假设位于一个未知的社区水库中。 职业发展奖（CDA）的支持将为Skinner博士提供 必要的基础和培训，使自己成为成功的VA生物医学和 实验室临床医生科学家着重于艰难梭菌的发病机理和流行病学。这 艰难梭菌的分子流行病学在数十年中一直在不断变化。这些转变 是影响菌株选择的潜在病理因素的结果。这种创新 项目将利用几十年来的艰难梭菌来了解允许的因素 对于一个菌株（Y组），要保持多数数十年。这些信息可能会进一步 用于了解哪些因素（即抗生素暴露）使退伍军人处于发展的风险 CDI并对艰难梭菌具有抗性的机制有更深入的了解 特定的抗生素。因此，该CDA的完成将为 Skinner博士和该项目的结果将用于支持Skinner博士的VA功绩评论 研究艰难梭菌对某些头孢菌素具有抗性的机制 抗菌剂。