title: 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.
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, and.
authors.forename: Warren E
authors.initials: WE
authors.lastname: Rose
authors.affiliation: Marshfield Clinic Research Foundation, Wisconsin.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Shukla
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, and.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Berti
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, and.
authors.forename: Mary S
authors.initials: MS
authors.lastname: Hayney
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, and.
authors.forename: Kelsey M
authors.initials: KM
authors.lastname: Henriquez
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ranzoni
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.affiliation: Departments of Medicine and Medical Microbiology/Immunology, University of Wisconsin School of Medicine and Public Health, Madison, and.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Proctor
authors.affiliation: Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla.
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.affiliation: Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla.
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016470:Bacteremia / Q000276:immunology / Q000401:mortality*; D058491:Bacterial Load; D015415:Biomarkers / Q000097:blood; D001769:Blood / Q000382:microbiology; D001808:Blood Vessels / Q000382:microbiology*; D003470:Culture Media / Q000737:chemistry; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D010457:Peptidoglycan / Q000097:blood / Q000276:immunology; D011446:Prospective Studies; D012307:Risk Factors; D013203:Staphylococcal Infections / Q000097:blood* / Q000276:immunology / Q000382:microbiology / Q000401:mortality*; D013211:Staphylococcus aureus / Q000276:immunology / Q000302:isolation & purification*
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D003470:Culture Media; C508609:IL10 protein, human; D010457:Peptidoglycan; D016753:Interleukin-10
keywords: Staphylococcus aureus; bacteremia; biomarker; inoculums.; mortality