The Epidemiology of Multi-Drug Resistant Enterobacteriaceae Infections in Childre

描述(申请人提供)：多重耐药(MDR)革兰氏阴性细菌，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，如大肠杆菌和克雷伯氏菌，在医学上是一个日益严重的问题。最近的文献表明，由于肠杆菌科多药耐药引起的感染在全球范围内急剧扩大，蔓延到儿童，但儿童的总体流行率尚不清楚。这些细菌抵抗治疗，并与显著的发病率和死亡率有关。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--比成年人本已稀少的数量要少。关于这些微生物的儿科研究很少发表，大多数都在美国以外，和/或只涉及单一机构或特定儿科人群的流行率。拉塔尼娅·洛根博士的职业目标是成为一名内科科学家，在传染病流行病学方面进行尖端研究。洛根博士的研究目标是掌握分子和临床流行病学方面的技能，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。拟议的指导性研究的目标是确定儿童产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菌株的遗传特征和亲缘关系；3)确定哪些暴露和宿主因素可预测儿童耐药肠杆菌科优势基因的定植和感染。因此，洛根博士的职业发展目标是获得所需的特定技能，以研究儿童肠杆菌科临床分离株的抗生素耐药性机制，重点是β-内酰胺类耐药性机制，并了解作为儿童感染预测因素的宿主因素和暴露。该项目的完成将需要结合肠杆菌科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，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和重要意义，因为它将极大地改善该领域对儿童对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细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脆弱人群中的传播。这些研究将直接为国家过敏和传染病研究所的使命做出贡献。

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.