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

Abstract

Background: Cell wall peptidoglycan stimulates interleukin 10 (IL-10) production in Staphylococcus aureus bacteremia (SaB) animal models, but clinical data are not available. This study evaluates the impact of intravascular bacterial cell numbers (ie, the level of bacteremia), in patients at the time of clinical presentation on IL-10 production and its association with S. aureus bacteremia (SaB) mortality.

Methods: Blood and isolates were collected in 133 consecutive SaB patients. Serum IL-10 was quantified by an electrochemoluminescence assay. Bacterial inoculum was measured in patient sera with elevated (n = 8) or low (n = 8) IL-10 using a magnetic bacterial capture assay. Staphylococcus aureus from these 2 groups were introduced into whole blood ex vivo to determine IL-10 production with variable inocula.

Results: IL-10 serum concentration was higher in SaB patient mortality (n = 27) vs survival (n = 106) (median, 36.0 pg/mL vs 10.4 pg/mL, respectively, P < .001). Patients with elevated IL-10 more often had endovascular SaB sources. The inoculum level of SaB was higher in patients with elevated serum IL-10 vs patients with low IL-10 (35.5 vs 0.5 median CFU/mL; P = .044). Ex vivo studies showed that 108 CFU/mL yielded greater IL-10 than did 103 CFU/mL (4.4 ± 1.8 vs 1.0 ± 0.6 pg/mL; P < .01).

Conclusions: 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.

Keywords: Staphylococcus aureus; bacteremia; biomarker; inoculums.; mortality.

Figure 1.

Cytokine serum concentrations at patient presentation with Staphylococcus aureus bacteremia stratified by in-hospital mortality or survival. Median and interquartile ranges for death and survival were compared by Mann-Whitney U test. All data points are presented in the panels for patient death, while only those outside of the interquartile range are presented for survival. A, Interleukin 10 (IL-10). B, Tumor necrosis factor alpha (TNF-α). C, Interleukin 1β (IL-1β). D, Ratio of IL-10 to TNF-α. E, Ratio of IL-10 to IL-1β.

Figure 2.

Distribution of patient interleukin 10 (IL-10) concentrations according to primary, secondary, or catheter-associated source of Staphylococcus aureus bacteremia. All patient data points are presented with the black symbols representing patients who survived and the white symbols as patient deaths. The bar in each category represents the median IL-10 concentration.