1205. Staphylococcal enterotoxin P predicts bacteremia in hospitalized patients colonized with methicillin-resistant Staphylococcus aureus
Session: Oral Abstract Session: Biomarkers of Infectious Diseases
Saturday, October 5, 2013: 9:30 AM
Room: The Moscone Center: 300
Background: Methicillin-resistant Staphylococcus aureus (MRSA) colonization is a strong predictor of later infection. Host factors are well described, but their influence on pathogen determinants of invasive disease have not been assessed.

Methods: We performed a nested case control study to evaluate host and pathogen determinants of MRSA bacteremia. Cases and controls were derived from an 8-ICU prospective adult cohort between 9/1/03 and 4/30/05 who underwent ICU admission MRSA screening and had all ICU, post-ICU, and readmission MRSA isolates prospectively collected. We selected MRSA carriers who did (cases) and did not (controls) develop subsequent MRSA bacteremia. After generating assembled genome sequences for the MRSA strains collected from these patients, we evaluated for the presence of 30 MRSA genes potentially associated with virulence and invasion. We assessed the association of these genes with MRSA bacteremia, controlling for host risk factors. Multivariable Cox proportional hazards regression determined host and pathogen characteristics associated with progression to MRSA bacteremia.

Results: There were 8,203 adult patients with 11,528 ICU admissions, with 1,578 MRSA isolates collected from 520 patients. We analyzed host and pathogen predictors for 33 MRSA carriers with subsequent MRSA bacteremia and 121 MRSA carriers without bacteremia. Significant predictors of MRSA bacteremia included a diagnosis of cancer, presence of a central venous catheter, hyperglycemia (glucose >200), and infection with a MRSA strain carrying the gene for staphylococcal enterotoxin P (sep). Receipt of an anti-MRSA medication had a significant protective effect.

Conclusion: Controlling for host determinants of MRSA infection, colonization with an MRSA strain carrying sep was a significant risk factor for developing MRSA bacteremia. This gene is carried by a bacteriophage along with other genes encoding proteins which help Staphylococcus aureus evade the host innate immune response. Identification of risk-adjusted genetic determinants of virulence may help to improve prediction of invasive disease and suggest new targets for therapeutic intervention.

Michael S. Calderwood, MD, MPH1,2, Christopher A. Desjardins, PhD3, George Sakoulas, MD4, Robert Nicol, PhD3, Andrea Dubois5, Mary L. Delaney5, Ken Kleinman, ScD1, Lisa A. Cosimi, MD2,3, Michael Feldgarden, PhD3, Andrew B. Onderdonk, PhD5, Bruce W. Birren, PhD3, Richard Platt, MD MS1, Susan S. Huang, MD, MPH, FIDSA6 and for the CDC Prevention Epicenter Program, (1)Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, (2)Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, (3)Broad Institute of MIT and Harvard, Cambridge, MA, (4)Department of Pediatrics, University of California San Diego School of Medicine, San Diego, CA, (5)Department of Pathology, Brigham and Women's Hospital, Boston, MA, (6)Division of Infectious Diseases and Health Policy Research Institute, University of California Irvine School of Medicine, Irvine, CA

Disclosures:

M. S. Calderwood, None

C. A. Desjardins, None

G. Sakoulas, None

R. Nicol, None

A. Dubois, None

M. L. Delaney, None

K. Kleinman, None

L. A. Cosimi, None

M. Feldgarden, None

A. B. Onderdonk, None

B. W. Birren, None

R. Platt, None

S. S. Huang, None

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