title: Staphylococcal enterotoxin P predicts bacteremia in hospitalized patients colonized with methicillin-resistant Staphylococcus aureus.
abstract: BACKGROUND
  Methicillin-resistant Staphylococcus aureus (MRSA) colonization predicts later infection, with both host and pathogen determinants of invasive disease.
  
  
  METHODS
  This nested case-control study evaluates predictors of MRSA bacteremia in an 8-intensive care unit (ICU) prospective adult cohort from 1 September 2003 through 30 April 2005 with active MRSA surveillance and collection of ICU, post-ICU, and readmission MRSA isolates. We selected MRSA carriers who did (cases) and those who did not (controls) develop MRSA bacteremia. Generating assembled genome sequences, we evaluated 30 MRSA genes potentially associated with virulence and invasion. Using multivariable Cox proportional hazards regression, we assessed the association of these genes with MRSA bacteremia, controlling for host risk factors.
  
  
  RESULTS
  We collected 1578 MRSA isolates from 520 patients. We analyzed host and pathogen factors for 33 cases and 121 controls. Predictors of MRSA bacteremia included a diagnosis of cancer, presence of a central venous catheter, hyperglycemia (glucose level, >200 mg/dL), 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.
  
  
  CONCLUSIONS
  In an analysis controlling for host factors, colonization with MRSA carrying sep increased the risk of MRSA bacteremia. Identification of risk-adjusted genetic determinants of virulence may help to improve prediction of invasive disease and suggest new targets for therapeutic intervention.
authors.affiliation: Division of Infectious Diseases.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Calderwood
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Desjardins
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: Robert
authors.initials: R
authors.lastname: Nicol
authors.forename: Andrea
authors.initials: A
authors.lastname: Dubois
authors.forename: Mary L
authors.initials: ML
authors.lastname: Delaney
authors.forename: Ken
authors.initials: K
authors.lastname: Kleinman
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cosimi
authors.forename: Michael
authors.initials: M
authors.lastname: Feldgarden
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Onderdonk
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Birren
authors.forename: Richard
authors.initials: R
authors.lastname: Platt
authors.forename: Susan S
authors.initials: SS
authors.lastname: Huang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000382:microbiology*; D001427:Bacterial Toxins / Q000235:genetics; D016022:Case-Control Studies; D004768:Enterotoxins / Q000235:genetics; D005260:Female; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D008875:Middle Aged; D012307:Risk Factors; D013203:Staphylococcal Infections / Q000382:microbiology*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins
keywords: Bacteremia; epidemiology; hospital infections; methicillin-resistant Staphylococcus aureus; microbial genetics
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