A Dysregulated Balance of Proinflammatory and Anti-Inflammatory Host Cytokine Response Early During Therapy Predicts Persistence and Mortality in Staphylococcus aureus Bacteremia*

Abstract

Sustained elevation of interleukin-10/tissue necrosis factor ratio at 72 hours suggests a dysregulated immune response and may be used to guide management to improve outcomes.

Risk stratification biomarkers for Staphylococcus aureus bacteraemia

“…identified IL‐10 is a potential biomarker to identify SAB patients at higher risk of severe clinical outcomes when measured prior to empiric antibiotic therapy . We show here that IL‐10 retains prognostic value when measured up to 3 days after initiation of effective antibiotic therapy, consistent with observations in an independent cohort . The unmet need is in patients with complicated SAB, who are most likely to fail standard‐of‐care antibiotics.…”

“…We did not replicate our prior finding that the combination of IL‐8 + CCL2, IL‐10 or other biomarkers in our panel was prognostic for 90‐day mortality . IL‐10, IL‐8 and IL‐6 have been associated with 30‐day or in‐hospital mortality . We also evaluated mortality over shorter windows of 30 days or in‐hospital, since comorbidities can be more impactful for the longer 90‐day outcome .…”

“…Of the previously published cytokines prognostic for persistent bacteraemia, this study validated IL‐10 and IL‐17A . High IL‐10 is associated with higher circulating levels of bacteria .…”

“…This is consistent with endovascular infection being a risk factor for persistent bacteraemia. Persistent bacteraemia increases mortality risk, and high IL‐17A and IL‐10 levels were associated with attributable mortality. We did not confirm the modest correlation between sE‐selectin and duration of positive blood cultures in our previous study (ρ = 0.30, P = 0.0007), which could be as a result of a technical limitation in this study resulting in 26% of patients assigned the upper limit of quantification value for sE‐selectin.…”

“…However, critical determinants of immune evasion in patients with SAB remain poorly understood and connections between the immune response and microbiological failure are lacking. Previous studies identified several candidate innate immunity biomarkers that were independently associated with mortality and prolonged SAB, supporting the utility of biomarkers to distinguish patients prone to developing severe disease . Such information would be particularly beneficial in guiding diagnostic work‐up of patients at increased risk of S. aureus infective endocarditis (IE), a disease that even with the best available treatments has contemporary in‐hospital mortality rates ranging from 25 to 46% …”