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.
Highlights
Staphylococcus aureus is an important opportunistic pathogen that causes a variety of infections, from relatively mild infections such as skin infections and food poisoning, to life-threatening conditions such as necrotizing pneumonia and osteomyelitis [1]
Course of S. aureus bacteremia To establish the LD50 inoculum in the S. aureus bacteremia model, groups of mice were intravenously infected with different inocula
In this study in mice, we determined whether blood culture, C-reactive protein (CRP), and cytokines are potential biomarkers for presence and outcome of S. aureus bacteremia
Summary
Staphylococcus aureus is an important opportunistic pathogen that causes a variety of infections, from relatively mild infections such as skin infections and food poisoning, to life-threatening conditions such as necrotizing pneumonia and osteomyelitis [1]. The invasive infections are frequently associated with S. aureus bacteremia [2]. Shorr et al showed that S. aureus was the most common bacterial isolate in 6,697 bloodstream infections in the USA, and S. aureus was more strongly associated with mortality than any other bacterial pathogen [3]. A clinically significant bacteremia is generally defined as the isolation of bacteria from one or more peripheral venous blood culture samples collected from a patient with associated relevant clinical symptoms of systemic infection as defined on the 2001 International Sepsis Definitions Conference [4]. Blood culture confirms the presence of bacteremia, and allows identification of the causative infectious agent. Knowledge of how to predict fatal outcome in patients with S. aureus bacteremia is currently lacking. To support clinical decisions on these issues, there is an urgent need for reliable markers that can be used as predictors of outcome of infection
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