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.

Public Health Relevance

Multi-drug resistant gram-negative bacteria (MDR-GNB), including Klebsiella pneumoniae carbapenemases (KPC) and extended spectrum beta-lactamase (ESBL) producing bacteria are resistant to most antibiotics and MDR-GNB infections in humans are associated with significant morbidity and mortality. The bacteria are rapidly spreading globally in all populations, recently including in children, although little is known abot infections in this vulnerable population. The overall goals of this multi-center, epidemiologic project are to define the prevalence, risk factors for acquisition, and outcomes of MDR-GNB infection in children, and to determine the genetic background and molecular epidemiology of these organisms in order to develop effective prevention strategies for children.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI112506-04
Application #
9262161
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Ernst, Nancy L
Project Start
2014-05-15
Project End
2019-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Rush University Medical Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
068610245
City
Chicago
State
IL
Country
United States
Zip Code
60612
Logan, Latania K; Medernach, Rachel L; Rispens, Jared R et al. (2018) Community Origins and Regional Differences Highlight Risk of Plasmid-Mediated Fluoroquinolone Resistant Enterobacteriaceae Infections in Children. Pediatr Infect Dis J :
Medernach, Rachel L; Logan, Latania K (2018) The Growing Threat of Antibiotic Resistance in Children. Infect Dis Clin North Am 32:1-17
Logan, Latania K; Gandra, Sumanth; Trett, Anna et al. (2018) Acinetobacter baumannii Resistance Trends in Children in the United States, 1999-2012. J Pediatric Infect Dis Soc :
Logan, Latania K; Nguyen, David C; Scaggs Huang, Felicia A et al. (2018) A Multi-Centered Case-Case-Control Study of Factors Associated with Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Infections in Children and Young Adults. Pediatr Infect Dis J :
Cocoros, Noelle M; Priebe, Gregory P; Logan, Latania K et al. (2017) A Pediatric Approach to Ventilator-Associated Events Surveillance. Infect Control Hosp Epidemiol 38:327-333
Logan, Latania K; Gandra, Sumanth; Mandal, Siddhartha et al. (2017) Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa in Children, United States, 1999-2012. J Pediatric Infect Dis Soc 6:352-359
Logan, Latania K; Weinstein, Robert A (2017) The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace. J Infect Dis 215:S28-S36
Viau, Roberto A; Kiedrowski, Lee M; Kreiswirth, Barry N et al. (2017) A Comparison of Molecular Typing Methods Applied to Enterobacter cloacae complex: hsp60 Sequencing, Rep-PCR, and MLST. Pathog Immun 2:23-33
Tamma, Pranita D; Suwantarat, Nuntra; Rudin, Susan D et al. (2016) First Report of a Verona Integron-Encoded Metallo-?-Lactamase-Producing Klebsiella pneumoniae Infection in a Child in the United States. J Pediatric Infect Dis Soc 5:e24-7
Cocoros, Noelle M; Kleinman, Ken; Priebe, Gregory P et al. (2016) Ventilator-Associated Events in Neonates and Children--A New Paradigm. Crit Care Med 44:14-22

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