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.