title: Distinctive cytokines as biomarkers predicting fatal outcome of severe Staphylococcus aureus bacteremia in mice.
abstract: Invasive Staphylococcus aureus infections are frequently associated with bacteraemia. To support clinical decisions on antibiotic therapy, there is an urgent need for reliable markers as predictors of infection outcome. In the present study in mice, bacteraemia was established by intravenous inoculation of a clinical S. aureus isolate at the LD50 inoculum. As potential biomarkers for fatal outcome, blood culture (qualitative and quantitative), serum levels of C-reactive protein (CRP), as well as 31 selected cytokines and chemokines were assessed during the first three days of infection. A positive S. aureus blood culture, the quantitative blood culture, CRP levels, and levels of eight cytokines were indicative for the presence of S. aureus bacteraemia. However, only tumor necrosis factor (TNF) α, interleukin (IL) 1α, and keratinocyte chemoattractant (KC; a functional homologue of human IL-8) were each significantly elevated in eventually non-surviving infected mice versus eventually surviving infected mice. In severe S. aureus bacteraemia in mice, TNF-α, IL-1α, and KC are biomarkers predicting fatal outcome of infection. KC was a biomarker elevated irrespective the progression of infection, which is very interesting regarding clinical application in view of the heterogeneity of patients experiencing bacteraemia in this respect.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Centre, Rotterdam, The Netherlands. s.vandenberg@erasmusmc.nl
authors.forename: Sanne
authors.initials: S
authors.lastname: van den Berg
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Marian T
authors.initials: MT
authors.lastname: ten Kate
authors.forename: Gerjo J
authors.initials: GJ
authors.lastname: de Knegt
authors.forename: Rob M
authors.initials: RM
authors.lastname: Verdijk
authors.forename: Henri A
authors.initials: HA
authors.lastname: Verbrugh
authors.forename: Jan L
authors.initials: JL
authors.lastname: Nouwen
authors.forename: Irma A J M
authors.initials: IA
authors.lastname: Bakker-Woudenberg
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D013047:Specific Pathogen-Free Organisms; D013203:Staphylococcal Infections / Q000097:blood*; D013211:Staphylococcus aureus
chemical_list: D015415:Biomarkers; D016207:Cytokines; D002097:C-Reactive Protein