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.

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。C.艰难梭菌感染（CDI） 据估计，每年在美国造成近45万例感染和3万例死亡。 自21世纪初以来，流行菌株被鉴定为限制性内切酶分析（REA） BI组，PCR核糖体型（RT）027（BI/RT 027）是CDI的最常见原因， 美国的然而，在过去的10年里， C.流行病学随着BI/RT 027患病率的下降，此外，还有 有证据表明，与医疗保健相关的CDI（HA-CDI）正在下降，与社区相关的CDI正在下降。 CDI（CA-CDI）正在增加。一种菌株被鉴定为REA Y组，通常与 RT 014和020 [Y（RT 014/020）]在美国流行，占美国 从80年代起就一直在使用CDI由于BI/RT 027相关CDI在过去10年中有所下降， Y（RT 014/020）相关的CDI稳步增加，目前占所有CDI的10-15%。与 随着CA-CDI的增加，越来越多的证据表明Y（RT 014/020）存在于未知的 社区水库尽管CA-CDI的流行已有数十年之久，而且越来越受到关注， Y（RT 014/020）的详细分子分析从未完成。因此，我们的建议 将完成详细的分子和临床分析，并结合严格的 Y（RT 014/020）和BI/RT 027的基因组分析，以评估导致 我们的总体假设是Y（RT 014/020）存在于未知的社区水库中。 职业发展奖（CDA）的支持将为斯金纳博士提供 必要的基础和培训，以建立自己作为一个成功的VA生物医学和 实验室临床科学家专注于C.很难的 C.分子流行病学在过去的几十年里，difficile一直在不断变化。这些转变 是影响品系选择的潜在病理因素的结果。这一创新 项目将利用C.几十年来，我们很难理解 一个菌株（REA Y组）保持地方性几十年。这些信息可以进一步 用于理解哪些因素（即，抗生素暴露）将退伍军人置于发展的风险之中 一个CDI，并提供了一个更深入的了解的机制，C。艰难梭菌耐药 特定的抗生素。因此，本综合发展区的完成将为 博士Skinner和本项目的结果将用于支持Skinner博士的VA Merit评审 应用该方法研究了C.艰难梭菌对某些头孢菌素有抗药性 抗菌剂