Epidemic Community-Acquired Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging infectious disease in previously healthy children and adults without risk factors for MRSA acquisition. These new community-acquired MRSA (CA-MRSA) strains differ from hospital-acquired MRSA (HA-MRSA) strains in that they are often susceptible to non-B-lactam antibiotics, cause disease similar to community-acquired methicillin-susceptible S. aureus (CA-MSSA), and contain the genes encoding the cytolytic toxin, Panton- Valentine leukocidin. When the genetic element responsible for the antibiotic susceptibility patterns in these CA-MRSA strains was characterized, now called """"""""staphylococcal chromosomal cassette mec"""""""" type IV or SCCmec type IV, it was realized that a distinct phenomenon had occurred not involving spread of HA-MRSA into the community. Outbreaks of skin and soft tissue infections, necrotizing pneumonia, and sepsis syndromes due to CA-MRSA have been reported with increasing frequency. We are seeking crucial information on how to prevent spread of these strains and how to treat infected and colonized individuals. The natural history of CA-MRSA colonization among household members and its association with infection are issues that must be defined in order to develop effective containment, preventative, and therapeutic strategies. In order to define the transmissibility of CA-MRSA strains, household contacts of an index case with CA- MRSA disease will be tested for colonization by CA-MRSA. Rates of CA-MRSA carriage among household contacts will be compared with rates of HA-MRSA carriage among household contacts of an index patient with HA-MRSA. The frequency with which CA-MRSA strains cause disease will be assessed prospectively by determining the secondary attack rate of disease and this will be compared to that of HA-MRSA. The predominant site of CA-MRSA will also be determined by culturing both the nose and the hand. All strains will be genetically characterized by pulsed-field gel electrophoresis, multi-locus sequence typing, SCCmec typing, and lukS-PV/lukF-PV PCR to determine the clonal repertoire of CA-MRSA strains and assess relatedness among household contacts. The knowledge to be gained from this study is crucial to guide further strategies to deal with the CA-MRSA epidemic. Defining the colonization frequency among household contacts of an index case, the secondary attack rate by CA-MRSA, and the predominant site of carriage will aid in development of containment, preventative, and therapeutic management guidelines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI067584-04
Application #
7866656
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Huntley, Clayton C
Project Start
2007-05-15
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
4
Fiscal Year
2010
Total Cost
$589,278
Indirect Cost
Name
University of Chicago
Department
Pediatrics
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Montgomery, Christopher P; David, Michael Z; Daum, Robert S (2015) Host factors that contribute to recurrent staphylococcal skin infection. Curr Opin Infect Dis 28:253-8
Miller, Loren G; Eells, Samantha J; David, Michael Z et al. (2015) Staphylococcus aureus skin infection recurrences among household members: an examination of host, behavioral, and pathogen-level predictors. Clin Infect Dis 60:753-63
Alam, Md Tauqeer; Read, Timothy D; Petit 3rd, Robert A et al. (2015) Transmission and microevolution of USA300 MRSA in U.S. households: evidence from whole-genome sequencing. MBio 6:e00054
Eells, Samantha J; David, Michael Z; Taylor, Alexis et al. (2014) Persistent environmental contamination with USA300 methicillin-resistant Staphylococcus aureus and other pathogenic strain types in households with S. aureus skin infections. Infect Control Hosp Epidemiol 35:1373-82
Miller, Loren G; Eells, Samantha J; Taylor, Alexis R et al. (2012) Staphylococcus aureus colonization among household contacts of patients with skin infections: risk factors, strain discordance, and complex ecology. Clin Infect Dis 54:1523-35
Daum, Robert S; Spellberg, Brad (2012) Progress toward a Staphylococcus aureus vaccine. Clin Infect Dis 54:560-7
Jo, Dae Sun; Montgomery, Christopher P; Yin, Shaohui et al. (2011) Improved oxacillin treatment outcomes in experimental skin and lung infection by a methicillin-resistant Staphylococcus aureus isolate with a vraSR operon deletion. Antimicrob Agents Chemother 55:2818-23
Mozzillo, K L; Ortiz, N; Miller, L G (2010) Patients with methicillin-resistant Staphylococcus aureus infection: twenty-first century lepers. J Hosp Infect 75:132-4
Montgomery, Christopher P; Boyle-Vavra, Susan; Daum, Robert S (2009) The arginine catabolic mobile element is not associated with enhanced virulence in experimental invasive disease caused by the community-associated methicillin-resistant Staphylococcus aureus USA300 genetic background. Infect Immun 77:2650-6
Montgomery, Christopher P; Daum, Robert S (2009) Transcription of inflammatory genes in the lung after infection with community-associated methicillin-resistant Staphylococcus aureus: a role for panton-valentine leukocidin? Infect Immun 77:2159-67

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