1148. A New Risk Factor for Disseminated Staphylococcus aureus Infection; Increased Neutrophil Chemotactic Signalling
Session: Poster Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011
Room: Poster Hall B1
Handouts
  • IDSA POSTER 1148 - disseminated SAB & chemokines.pdf (493.7 kB)
  • Background: 

    Disseminated S. aureus infection is common and is not associated with bacterial virulence factors or lineage. Animal studies demonstrate excessive chemokine-mediated neutrophil recruitment is associated with increased bacterial load and mortality. The hypothesis that disseminated S. aureus bacteraemia is associated with elevated circulating levels of neutrophil chemotaxins was investigated.

    Methods: 

    Circulating levels of neutrophil chemotaxins were measured by Luminex® bead-array in patients with S. aureus bacteraemia. Disseminated infection was defined as seeding of infection beyond the primary focus. Patients were followed for 30 days or until death or discharge. S. aureus isolates were strain typed.

    Results: 

    80 patients were recruited. Patients with disseminated infection (n=16) had lower levels of CXCL5 (1157 vs. 2076pg/ml, p=0.01) and higher levels of IL6 (64.7 vs. 18.2pg/ml, p=0.01) and G-CSF (35.6 vs. 14.3, p=0.06). Dissemination was associated with a longer time to defervescence (3.8 vs. 2.2 days, p=0.02), a higher peripheral leukocyte count (20.7 vs. 16.2 x109/L, p=0.05) and community-acquired infection (59% vs. 22%, p<0.01). Lineages of isolates causing disseminated and non-disseminated infection were similar (p=0.43).

    Conclusion: IL6, G-CSF and CXCL5 are neutrophil chemotaxins but act via different pathways. IL6 and G-CSF enhance neutrophil mobilisation from bone marrow. CXCL5 binding to phagocyte receptor CXCR2 and to endothelial Duffy antigen receptor for chemokines (DARC) results in CXCL5 translocation across endothelial cells and neutrophil extravasation. Low circulating CXCL5 and elevated G-CSF has been described in haemolytic-uraemic syndrome, with disease pathology due to increased neutrophil migration from circulation into renal tissue. S. aureus survives within phagocytes. It is possible that, in bacteraemic patients, IL6 and G-CSF promote phagocytosis of circulating S. aureus and CXCL5 increases migration of S. aureus-laden neutrophils into tissues. CXCL5 and DARC gene polymorphisms influence expression and stains inhibit CXCL5 synthesis. The hypothesis that disseminated infection occurs more frequently in individuals with increased CXCL5 and/or DARC expression is being investigated.


    Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

    Jonathan Lambourne, MD, PhD1, Richard Holliman, MD, MSc, DSc1,2 and Jodi Lindsay, MSc, PhD1, (1)Centre for Infection, Division of Cellular & Molecular Medicine, St George’s University of London, London, United Kingdom, (2)Department of Microbiology, St George’s Healthcare NHS Trust, London, United Kingdom

    Disclosures:

    J. Lambourne, None

    R. Holliman, None

    J. Lindsay, None

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.