The Epidemiology of Multi-Drug Resistant Enterobacteriaceae Infections in Childre

描述（由申请人提供）：多重耐药（MDR）革兰氏阴性菌，包括肺炎克雷伯菌碳青霉烯酶（KPC）和产生超广谱β-内酰胺酶（ESBL）的肠杆菌科细菌，例如大肠杆菌和克雷伯氏菌，代表了医学中日益严重的问题。最近的文献表明，耐多药肠杆菌科细菌感染在全球范围内急剧扩大，并延伸至儿童，但儿童的总体患病率尚不清楚。这些细菌对治疗有抵抗力，并且与显着的发病率和死亡率相关。由于缺乏抗生素，儿童耐多药肠杆菌科感染的治疗面临着极大的挑战——比成人可用的抗生素数量还要少。关于这些生物体的儿科研究很少发表，其中大多数是在美国境外进行的和/或仅针对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领域进行前沿研究的医师科学家。 Logan 博士的研究目标是获得分子和临床流行病学技能，以对儿童耐多药肠杆菌科细菌的医院和社区流行病学进行独立研究。拟议的指导研究的目标是确定儿童中产 ESBL 和 KPC 肠杆菌科细菌的临床和分子流行病学。这个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细菌分离株中 ESBL 和 KPC 表型的遗传基础； 2) 确定优势ESBL和KPC菌株的遗传性状和相关性； 3) 确定哪些暴露和宿主因素可作为儿童耐药肠杆菌科显性基因型定植和感染的预测因子。因此，Logan 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机制所需的具体技能，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。该项目的完成将需要结合分子流行病学和肠杆菌科比较基因组学的传统和新颖的尖端技术，以及临床流行病学研究，以确定导致儿童感染的宿主因素和暴露。这项研究具有创新性且意义重大，因为它将大大改善该领域对儿童这些细菌的有限了解。从长远来看，洛根博士的目标是在全国范围内研究儿童耐多药革兰氏阴性菌的分子和临床流行病学，并最终设计出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群体中的传播。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.