This application for a K23 Career Development Award proposes a four-year program to provide the candidate with mentored training in patient-oriented research, protected time, and coursework in advanced epidemiology, biostatistics, and community-based participatory research. The long- term goals of the candidate are to become an independent physician-scientist at an academic medical center, investigating the epidemiology of community-associated methicillin-resistant Staphylococcus aureus (CA- MRSA) and the molecular mechanisms driving staphylococcal transmission, leading to the development of novel methods for the prevention and treatment of CA-MRSA infections. The proposed work will be performed at Washington University and St. Louis Children's Hospital under the mentorship of Victoria Fraser, M.D., an accomplished clinical investigator in infectious diseases epidemiology. A faculty advisory committee consisting of experienced clinical and basic researchers will facilitate the candidate's research and career development. Epidemic strains of CA-MRSA cause significant morbidity and mortality among immunocompetent individuals, especially children, ranging from superficial cutaneous abscesses to invasive infections. CA- MRSA infections have been observed to cluster in households. However, the interplay of household colonization pressure and transmission, hygiene and behavioral risk factors, and environmental contamination influencing CA-MRSA colonization and infection has not been specified. These risk factors must be defined to develop evidence-based guidelines to interrupt CA-MRSA transmission and prevent infections. Understanding the impact of these variables will inform practice to improve health and decrease the burden of CA-MRSA colonization and disease. Preliminary studies demonstrate that household members of index patients with CA-MRSA infection and colonization are also colonized with CA-MRSA. A one-year prospective cohort study of 135 pediatric patients with CA-MRSA infection and their household members will be performed. Using mixed effects logistic regression modeling, the relationships among risk factors at multiple levels (including household colonization pressure, host behavioral practices, and contamination of household surfaces) will be elucidated to identify factors conferring the greatest risks for CA-MRSA colonization, infection, and transmission. Three integrated specific aims are proposed: 1) Define the transmission dynamics of CA-MRSA colonization and infection among pediatric index patients and their household contacts over one year, and determine the contribution of CA-MRSA colonization to subsequent CA-MRSA infection;2) Identify hygiene and behavioral practices contributing to CA-MRSA transmission, colonization, and infection within households;and 3) Determine the role of environmental contamination and household characteristics in household CA-MRSA transmission. PROJECT NARRATIVE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a significant public health problem causing infections in healthy people. The proposed research will define how CA-MRSA is transmitted within households and identify risk factors for colonization and infection. The results will be used to design interventions to prevent CA-MRSA infections.

Public Health Relevance

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a significant public health problem causing infections in healthy people. The proposed research will define how CA-MRSA is transmitted within households and identify risk factors for colonization and infection. The results will be used to design interventions to prevent CA-MRSA infections.

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 #
5K23AI091690-03
Application #
8475541
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Huntley, Clayton C
Project Start
2011-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$126,506
Indirect Cost
$9,223
Name
Washington University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Fritz, Stephanie A; Hogan, Patrick G; Singh, Lauren N et al. (2014) Contamination of environmental surfaces with Staphylococcus aureus in households with children infected with methicillin-resistant S aureus. JAMA Pediatr 168:1030-8
Rodriguez, Marcela; Hogan, Patrick G; Burnham, Carey-Ann D et al. (2014) Molecular epidemiology of Staphylococcus aureus in households of children with community-associated S aureus skin and soft tissue infections. J Pediatr 164:105-11
Gurnee, Emily A; Ndao, I Malick; McGhee, Jessica E et al. (2014) Fecal carriage of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus in healthy children. Antimicrob Agents Chemother 58:1261-2
Fritz, Stephanie A; Hogan, Patrick G; Camins, Bernard C et al. (2013) Mupirocin and chlorhexidine resistance in Staphylococcus aureus in patients with community-onset skin and soft tissue infections. Antimicrob Agents Chemother 57:559-68
Fritz, Stephanie A; Tiemann, Kristin M; Hogan, Patrick G et al. (2013) A serologic correlate of protective immunity against community-onset Staphylococcus aureus infection. Clin Infect Dis 56:1554-61