Evidence-Based Medicine for Enhanced Management of Complicated Staphylococcus Aureus Infections: Can We Do Better?
Emergency and Critical Care
Staphylococcus aureus is a leading cause of hospital and community acquired bacteremia. Our results suggest a link between staphylococcal superantigens and patient outcomes. The presence of multiple superantigen genes correlates with increased IL-2 production and worse patient outcomes with increased ICU admission, sepsis, and mortality. Furthermore, the risk of methicillin-resistant S. aureus (MRSA) infection is increased in patients with high T cell activation profiles. Definition of superantigen gene profiles in patients admitted with S. aureus bacteremia could facilitate identification of patients at high risk of a poor outcome and the risk of an MRSA infection. Treatment could then be specifically tailored to the probable risk of these outcomes based on the superantigen gene profile.
Background: Staphylococcus aureus (S. aureus) is a leading cause of hospital and community acquired bacteremia yet bacterial factors that contribute to poor outcome are not well understood. We hypothesize that superantigens contribute to poor outcomes in S. aureus bacteremia. Methods: Genomic DNA from bacterial isolates from 33 S. aureus bacteremia patients was analyzed for 23 staphylococcal superantigen genes. Bacterial supernatant proteins were isolated and used to stimulate human peripheral blood mononuclear cells from healthy donors for 3 days. An ELISA was used to quantify IL-2 concentrations as a marker of T cell proliferation and activation. Results: At least one superantigen gene was detected in all isolates tested. Some isolates had an impressive repertoire of superantigen genes while others only had one or two. IL-2 results indicate that bacterial isolates with many superantigen genes caused massive T cell activation (high activators) versus isolates with few superantigen genes (low activators). In the low activation group, 27% patients exhibited sepsis or septic shock versus 59% in the high activation group. Similarly, the low activation group had no mortality and 9% ICU admission rate compared to 27% and 32%, respectively, in the high activation group. Also, the high activation group had a higher incidence of methicillin-resistant S. aureus (MRSA) infection at 45% versus 9% in the low activation group. Conclusions: The presence of multiple superantigen genes correlates with greater IL-2 production, consequent T cell activation, worse patient outcomes with increased ICU admission, sepsis, mortality and increased risk of MRSA. Future Directions: We will test our results in a mouse model of S. aureus bacteremia to determine if neutralization of superantigens will improve outcomes.