Increased endovascular Staphylococcus aureus inoculum is the link between elevated serum interleukin 10 concentrations and mortality in patients with bacteremia

Rose, Warren E., Shukla, Sanjay K., Berti, Andrew D., Hayney, Mary S., Henriquez, Kelsey M., Ranzoni, Andrea, Cooper, Matthew A., Proctor, Richard A., Nizet, Victor and Sakoulas, George (2017) Increased endovascular Staphylococcus aureus inoculum is the link between elevated serum interleukin 10 concentrations and mortality in patients with bacteremia. Clinical Infectious Diseases, 64 10: 1406-1412. doi:10.1093/cid/cix157


Author Rose, Warren E.
Shukla, Sanjay K.
Berti, Andrew D.
Hayney, Mary S.
Henriquez, Kelsey M.
Ranzoni, Andrea
Cooper, Matthew A.
Proctor, Richard A.
Nizet, Victor
Sakoulas, George
Title Increased endovascular Staphylococcus aureus inoculum is the link between elevated serum interleukin 10 concentrations and mortality in patients with bacteremia
Formatted title
Increased endovascular Staphylococcus aureus inoculum is the link between elevated serum interleukin 10 concentrations and mortality in patients with bacteremia
Journal name Clinical Infectious Diseases   Check publisher's open access policy
ISSN 1537-6591
1058-4838
Publication date 2017-05-15
Sub-type Article (original research)
DOI 10.1093/cid/cix157
Open Access Status Not yet assessed
Volume 64
Issue 10
Start page 1406
End page 1412
Total pages 7
Place of publication Cary, NC, United States
Publisher Oxford University Press
Language eng
Abstract 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.

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.

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).

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.
Formatted 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.
Keyword Biomarker
Staphylococcus aureus
Bacteremia
Inoculums
Mortality
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID R01 HL125352
U01 AI124316
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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