We are proposing studies utilizing the patients enrolled in the DMID-funded """"""""Randomized, Double-Blind Trial of Clindamycin, Trimethoprim-Sulfamethoxazole, or Placebo for Uncomplicated Skin and Soft Tissue Infections Caused by Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA)."""""""" This contract by NIAID to the Co-PI at the University of Chicago as well as investigators at the University of California/San Francisco, Harbor-University of California/Los Angeles, has provided a unique opportunity to explore unaddressed issues. About 375 children and adults with skin and soft tissue infections (SIs) will be enrolled for a period of three years at the University of Chicago. Preliminary data indicate that about 84% of enrollees will have a S. aureus SI, providing a unique opportunity to perform additional research addressing the underlying cause for increased susceptibility to SIs in the general population. In the last decade the incidence and frequency of MRSA infections has increased exponentially, particularly among otherwise healthy individuals, to the extent that CA-MRSA has become epidemic in the US and is now a public health imperative. The recognition that CA-MRSA strains can both spread rapidly and cause severe disease mandates a need for urgent investigation to understand the molecular microbial pathogenicity and underlying host immune responses. Accordingly, we have assembled a multidisciplinary team of microbiologists, infectious disease experts, and immunologists to explore simultaneously several areas likely to yield important insights into the biology of the CA-MRSA epidemic, with a focus on the role of host immune responses in CA-MRSA infection. Studies detailed in this proposal will provide substantial insight into the contributions of host innate and adaptive mechanisms to infection susceptibility. It is hoped that new information will guide novel therapeutic and preventive strategies to combat CA-MRSA infection.

Public Health Relevance

The recognition that community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) can both spread rapidly and cause severe skin infections mandates a need for urgent investigation of the molecular microbial pathogenicity and host immune responses contributing to this epidemic. A contract was awarded by DMID to the co-PI at the University of Chicago to compare treatment strategies in skin infections in the Emergency Department. In these ancillary studies, we propose to determine whether increased susceptibility to CA-MRSA skin infections by a subset of the population is due to inherent defects in host innate and T cell immune responses and/or to specific properties of CA-MRSA to modulate immune responses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR059414-03
Application #
8271253
Study Section
Special Emphasis Panel (ZAR1-CHW (M1))
Program Officer
Cibotti, Ricardo
Project Start
2010-09-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
3
Fiscal Year
2012
Total Cost
$336,960
Indirect Cost
$120,960
Name
University of Chicago
Department
Pediatrics
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Alegre, Maria-Luisa; Chen, Luqiu; David, Michael Z et al. (2016) Impact of Staphylococcus aureus USA300 Colonization and Skin Infections on Systemic Immune Responses in Humans. J Immunol 197:1118-26
Montgomery, Christopher P; Daniels, Melvin; Zhao, Fan et al. (2014) Protective immunity against recurrent Staphylococcus aureus skin infection requires antibody and interleukin-17A. Infect Immun 82:2125-34
Montgomery, Christopher P; Daniels, Melvin D; Zhao, Fan et al. (2013) Local inflammation exacerbates the severity of Staphylococcus aureus skin infection. PLoS One 8:e69508