The Epidemiology of Multi-Drug Resistant Enterobacteriaceae Infections in Childre

性状（由申请方提供）：多重耐药（MDR）革兰氏阴性菌，包括产碳青霉烯酶（KPC）和超广谱β-内酰胺酶（ESBL）的肠杆菌科，如大肠埃希菌。大肠杆菌和克雷伯氏菌代表了医学上不断升级的问题。最近的文献表明，由于MDR肠杆菌科感染在全球范围内的急剧扩张延伸到儿童，但总体儿科患病率尚不清楚。这些细菌抵抗治疗并与显著的发病率和死亡率相关。由于缺乏抗生素，儿童MDR肠杆菌科感染的治疗面临着极大的挑战-比成年人已经稀缺的数量少。关于这些微生物的儿科研究很少发表，大多数研究都在美国以外和/或仅涉及单个机构或特定儿科人群的患病率。Latania Logan博士的职业目标是成为一名在传染病流行病学方面进行前沿研究的医生科学家。Logan博士的研究目标是获得分子和临床流行病学方面的技能，对儿童MDR肠杆菌科的医院和社区流行病学进行独立研究。建议指导研究的目标是确定儿童产ESBL和KPC肠杆菌科的临床和分子流行病学。该多中心医疗保健项目的具体目标是：1）确定来自芝加哥地区多个中心的儿童肠杆菌科分离株中ESBL和KPC表型的遗传基础; 2）确定ESBL和KPC优势菌株的遗传特征和相关性;和3）确定哪些暴露和宿主因素可作为耐药肠杆菌科优势基因型内定植和感染的预测因子小儿因此，洛根博士的职业发展目标是获得研究儿童肠杆菌科临床分离株抗生素耐药性机制所需的特定技能，重点是β-内酰胺耐药机制，并了解作为儿童感染预测因子的宿主因素和暴露。要完成这一项目，就需要将肠杆菌科的分子流行病学和比较基因组学方面的传统和新的尖端技术与临床流行病学研究结合起来，沿着以确定导致儿童感染的宿主因素和接触情况。这项研究具有创新性和重要性，因为它将大大改善该领域对儿童中这些细菌的有限了解。从长远来看，Logan博士的目标是在全国范围内研究儿童中MDR革兰氏阴性菌的分子和临床流行病学，并最终设计有效的治疗干预措施和预防策略，以减缓这些病原体在弱势人群中的传播。这些研究将直接有助于国家过敏和传染病研究所的使命。

DESCRIPTION (provided by applicant): Multi-drug resistant (MDR) gram-negative bacteria including Klebsiella pneumoniae carbapenemase (KPC) and extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae such as E. coli and Klebsiella represent an escalating problem in medicine. Recent literature suggests the dramatic global expansion of infections due to MDR Enterobacteriaceae extends to children, but the overall pediatric prevalence is unknown. These bacteria resist treatment and are associated with significant morbidity and mortality. Treatment of MDR Enterobacteriaceae infections in children poses extreme challenges due to a lack of antibiotics -- fewer than the already scarce number available to adults. Few pediatric studies on these organisms have been published, with the majority based outside of the U.S. and/or only addressing prevalence at a single institution or in a specific pediatric population. Dr. Latania Logan's career goal is to become a physician-scientist who conducts cutting edge research in the epidemiology of infectious diseases. Dr. Logan's research goal is to acquire skills in molecular and clinical epidemiology to conduct independent research on the hospital and community epidemiology of MDR Enterobacteriaceae in children. The goal of the proposed mentored research is to define the clinical and molecular epidemiology of ESBL and KPC producing Enterobacteriaceae in children. The specific aims of this multi-center healthcare project are: 1) To determine the genetic basis of ESBL and KPC phenotypes in Enterobacteriaceae isolates from children from multiple centers in the Chicago area; 2) To determine genetic traits and relatedness of dominant ESBL and KPC strains; and 3) To identify which exposures and host factors serve as predictors of colonization and infection within dominant genotypes of resistant Enterobacteriaceae in children. Therefore, Dr. Logan's career development objectives are to acquire the specific skills needed to study the mechanisms of antibiotic resistance in clinical isolates of Enterobacteriaceae in children, with a focus on beta-lactam resistance mechanisms, and to understand the host factors and exposures that serve as predictors of infection in children. The completion of this project will require the combination of traditional and novel, cutting-edge techniques in molecular epidemiology and comparative genomics of Enterobacteriaceae, along with clinical epidemiology studies to define host factors and exposures leading to infection in children. This research is innovative and significant because it will substantially improve the field's limited understanding of these bacteria in children. In the long-term, Dr. Logan's goal is to nationally study the molecular and clinical epidemiology MDR gram-negative bacteria in children, and to ultimately design effective therapeutic interventions and prevention strategies to slow spread of these pathogens in a vulnerable population. These studies will directly contribute to the mission of the National Institute of Allergy and Infectious Diseases.