The purpose of this K23 career development proposal is to obtain additional resources, protected time, and training so that I can become an independent, patient-oriented researcher, focusing on C. difficile-associated disease (CDAD) and infections in hematopoietic stem cell transplant (HSCT) recipients. I am in the process of obtaining a Masters of Science in Public Health and I am taking courses in epidemiology, ethical conduct of research, and advanced statistical analysis. I have a mentor, Dr. Victoria Fraser, who is an expert in the field of nosocomial infection outcomes and prevention and a faculty advisory committee to facilitate my research and career development. CDAD is the most common cause of nosocomial, infectious diarrhea and causes increased morbidity, length of stay, and costs. HSCT recipients have many risk factors for CDAD and are extremely immunosuppressed. They are at high risk for developing CDAD and severe CDAD. However, there are few studies of CDAD in this patient population, and the studies published are limited by small sample sizes and inadequate study design.
The Specific Aims of the research proposal are to: 1) Determine the risk factors and clinical outcomes of CDAD following allogeneic HSCT, specifically whether granulocyte colony stimulating factor (GCSF) reduces the risk of CDAD and the relationship between CDAD and subsequent development of graft vs. host disease (GVHD). To achieve this aim I will perform a 3-year prospective longitudinal cohort study of allogeneic HSCT recipients. 2) Determine how donor immunity to C. difficile and changes in HSCT recipient serum levels of C. difficile anti-toxin antibodies influence risk and outcomes of CDAD in allogeneic HSCT recipients. 3) Determine the transmission dynamics of C. difficile on a HSCT unit by prospectively culturing patients, the environment and health care workers'hands for C. difficile. Multivariate analysis will be performed to evaluate the relative impact of asymptomatically colonized patients, environmental contamination and health care workers'hands as drivers of CDAD acquisition and transmission.

Public Health Relevance

Clostridium difficile is a healthcare-associated, antibiotic resistant pathogen of increasing importance in the US and abroad. The proposed research will contribute to our knowledge of the pathogenesis and transmission of Clostridium difficile in stem cell transplant recipients and the general population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI065806-02
Application #
7758254
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Wachtel, Marian R
Project Start
2009-02-01
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
2
Fiscal Year
2010
Total Cost
$125,028
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Dubberke, Erik R; Reske, Kimberly A; Seiler, Sondra et al. (2015) Risk Factors for Acquisition and Loss of Clostridium difficile Colonization in Hospitalized Patients. Antimicrob Agents Chemother 59:4533-43
Zhou, Yanjiao; Burnham, Carey-Ann D; Hink, Tiffany et al. (2014) Phenotypic and genotypic analysis of Clostridium difficile isolates: a single-center study. J Clin Microbiol 52:4260-6
Lanzas, Cristina; Dubberke, Erik R (2014) Effectiveness of screening hospital admissions to detect asymptomatic carriers of Clostridium difficile: a modeling evaluation. Infect Control Hosp Epidemiol 35:1043-50
Alasmari, Faisal; Seiler, Sondra M; Hink, Tiffany et al. (2014) Prevalence and risk factors for asymptomatic Clostridium difficile carriage. Clin Infect Dis 59:216-22
Westblade, Lars F; Chamberland, Robin R; MacCannell, Duncan et al. (2013) Development and evaluation of a novel, semiautomated Clostridium difficile typing platform. J Clin Microbiol 51:621-4
Kasper, Amelia M; Nyazee, Humaa A; Yokoe, Deborah S et al. (2012) A multicenter study of Clostridium difficile infection-related colectomy, 2000-2006. Infect Control Hosp Epidemiol 33:470-6
Murphy, Courtney R; Avery, Taliser R; Dubberke, Erik R et al. (2012) Frequent hospital readmissions for Clostridium difficile infection and the impact on estimates of hospital-associated C. difficile burden. Infect Control Hosp Epidemiol 33:20-8
Dubberke, Erik R; Nyazee, Humaa A; Yokoe, Deborah S et al. (2012) Implementing automated surveillance for tracking Clostridium difficile infection at multiple healthcare facilities. Infect Control Hosp Epidemiol 33:305-8
Han, Zhuolin; McMullen, Kathleen M; Russo, Anthony J et al. (2012) A Clostridium difficile infection ""intervention"": change in toxin assay results in fewer C difficile infection cases without changes in patient outcomes. Am J Infect Control 40:349-53
Dubberke, Erik R; Yan, Yan; Reske, Kimberly A et al. (2011) Development and validation of a Clostridium difficile infection risk prediction model. Infect Control Hosp Epidemiol 32:360-6

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