The overall goal of this K01 proposal is to support Jennifer Han, M.D., M.S.C.E., to become an independent investigator in the field of healthcare-associated infections and antimicrobia-resistant organisms, with a specific focus on the post-acute care setting. Antimicrobial resistance is a critical public health problem and is associated with significant morbidity, mortality, and healthcare costs. Post-acute care settings, and long-term acute care hospitals (LTACHs) in particular, are increasingly important sites of clinical care in the United States. Given high rates of antimicrobial and medical device use, prolonged lengths of stay, and complex patient populations with acute medical needs, patients in LTACHs are at significant risk for infection with antimicrobial-resistant organisms. However, despite th dramatic and continued rise in the LTACH population in recent years, there are very few data on the epidemiology of antimicrobial-resistant organisms in this healthcare setting. In this proposal, the candidate will elucidate the epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) in the LTACH setting. The prevalence of CRKP in the past decade has increased at an alarming rate such that CRKP is now endemic in many parts of the world, including areas of the United States. Given the lack of effective antimicrobal treatment options, as well as high associated mortality rates, CRKP represent perhaps the most significant challenge in antimicrobial-resistant organisms. This proposal adopts an interdisciplinary approach, and will link the clinical and molecular epidemiology of CRKP to substantially improve the understanding of CRKP infections in the LTACH setting.
The specific aims of this proposal are:
Aim 1 : to provide comprehensive genotypic and phenotypic characterization of CRKP isolates (including resistance mechanisms) from a large, nationally-widespread network of LTACHs.
Aim 2 : to elucidate risk factors for infectio with CRKP in the LTACH setting.
Aim 3 : to evaluate the clinical impact of CRKP infection in the LTACH setting. The hypotheses for these aims are: 1) the phenotypic and genotypic characteristics of CRKP isolates will be rigorously identified~ 2) prior carbapenem use is associated with CRKP infection~ and 3) CRKP infections are associated with increased mortality. The results of the proposed research will significantly infom future intervention studies with the goal of decreasing infection-associated morbidity an mortality in LTACHs. This proposal represents a five-year comprehensive mentoring, research, and didactic plan to transition the candidate to a successful independent investigator in antimicrobial resistance. At the conclusion of the award period, the candidate will have contributed substantially to knowledge of the epidemiology of CRKP infection in a healthcare setting of increasing importance. In addition, the candidate will be poised o become a leader in conducting clinical epidemiologic research to limit the emergence of antimicrobial-resistant organisms in post-acute care settings as well as improve associated clinical outcomes.

Public Health Relevance

Infections due to carbapenem-resistant Klebsiella pneumoniae (CRKP) have rapidly emerged as a significant public health threat, and are associated with substantial morbidity and mortality. This research proposal will evaluate the clinical and molecular epidemiology f CRKP infections in the long-term acute care hospital (LTACH) setting. Our project will yield important information for clinical management and antimicrobial stewardship efforts geared toward limiting the emergence of CRKP in a healthcare setting of increasing importance.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Scientist Development Award - Research & Training (K01)
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Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Korpela, Jukka K
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University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
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Anesi, Judith A; Lautenbach, Ebbing; Nachamkin, Irving et al. (2018) Poor clinical outcomes associated with community-onset urinary tract infections due to extended-spectrum cephalosporin-resistant Enterobacteriaceae. Infect Control Hosp Epidemiol 39:1431-1435
Simner, Patricia J; Goodman, Katherine E; Carroll, Karen C et al. (2018) Using Patient Risk Factors to Identify Whether Carbapenem-Resistant Enterobacteriaceae Infections Are Caused by Carbapenemase-Producing Organisms. Open Forum Infect Dis 5:ofy094
Chiotos, Kathleen; Tamma, Pranita D; Flett, Kelly B et al. (2018) Increased 30-Day Mortality Associated With Carbapenem-Resistant Enterobacteriaceae in Children. Open Forum Infect Dis 5:ofy222
Tamma, Pranita D; Pierce, Virginia M; Cosgrove, Sara E et al. (2018) Can the Ceftriaxone Breakpoints Be Increased Without Compromising Patient Outcomes? Open Forum Infect Dis 5:ofy139
Kelly, Brendan J; Lautenbach, Ebbing; Nachamkin, Irving et al. (2018) Combined Biomarkers Predict Acute Mortality Among Critically Ill Patients With Suspected Sepsis. Crit Care Med 46:1106-1113
Chotiprasitsakul, Darunee; Han, Jennifer H; Cosgrove, Sara E et al. (2018) Comparing the Outcomes of Adults With Enterobacteriaceae Bacteremia Receiving Short-Course Versus Prolonged-Course Antibiotic Therapy in a Multicenter, Propensity Score-Matched Cohort. Clin Infect Dis 66:172-177
Ziegler, Matthew; Landsburg, Daniel; Pegues, David et al. (2018) Clinical Characteristics and Outcomes of Hematologic Malignancy Patients With Positive Clostridium difficile Toxin Immunoassay Versus Polymerase Chain Reaction Test Results. Infect Control Hosp Epidemiol 39:863-866
Han, Jennifer H; Goldstein, Ellie J C; Wise, Jacqueleen et al. (2017) Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae in a Network of Long-Term Acute Care Hospitals. Clin Infect Dis 64:839-844
Han, Jennifer H; Garrigan, Charles; Johnston, Brian et al. (2017) Epidemiology and characteristics of Escherichia coli sequence type 131 (ST131) from long-term care facility residents colonized intestinally with fluoroquinolone-resistant Escherichia coli. Diagn Microbiol Infect Dis 87:275-280
Chiotos, Kathleen; Tamma, Pranita D; Flett, Kelly B et al. (2017) Multicenter Study of the Risk Factors for Colonization or Infection with Carbapenem-Resistant Enterobacteriaceae in Children. Antimicrob Agents Chemother 61:

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