Increased Endovascular Staphylococcus aureus Inoculum Is the Link Between Elevated Serum Interleukin 10 Concentrations and Mortality in Patients With Bacteremia

Abstract

Elevated IL-10 serum concentrations at clinical presentation of SaB were highly associated with mortality. High intravascular peptidoglycan concentration, driven by a higher level of bacteremia, is a key mediator of IL-10 anti-inflammatory response that portends poor clinical outcome. Using IL-10 as an initial biomarker, clinicians may consider more aggressive antimicrobials for rapid bacterial load reduction in high-risk SaB patients.

Risk stratification biomarkers for Staphylococcus aureus bacteraemia

“…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 . The validation of IL‐17A is noteworthy given that few biomarkers to aid in the diagnosis or prognosis of IE have been validated across cohorts (reviewed by Snipsøyr et al ).…”

“…IL-17A was the only significant predictor identified by lasso modelling and was also the largest contributor in random forest modelling, when predicting either the presence of IE or any endovascular infection (Supplementary figure 2d, e). IL-17A and other biomarkers weighted in the random forest model (IL-10, previously reported to be elevated in IE, 5,7 sE-selectin and IL-1RN) were intercorrelated (Supplementary figure 2f, Spearman q > 0.4).…”

“…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% …”

“…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. 1,[4][5][6][7] 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%. [8][9][10] To investigate the contribution of the differential immune response to SAB disease severity, we previously identified biomarker profiles associated with mortality and persistent bacteraemia in a twophase case-control study of patients with complicated SAB.…”