Complement levels in patients with bloodstream infection due to Staphylococcus aureus or Gram-negative bacteria
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ORIGINAL ARTICLE
Complement levels in patients with bloodstream infection due to Staphylococcus aureus or Gram-negative bacteria Emily M. Eichenberger 1 & Michael Dagher 1 & Felicia Ruffin 1 & Lawrence Park 1,2 & Lisa Hersh 3 & Sumathi Sivapalasingam 3 & Vance G. Fowler Jr 1 & Brinda C. Prasad 3 Received: 10 March 2020 / Accepted: 15 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The complement system is a vital component of the innate immune system, though its role in bacteremia is poorly understood. We present complement levels in Staphylococcus aureus bacteremia (SAB) and Gram-negative bacteremia (GNB) and describe observed associations of complement levels with clinical outcomes. Complement and cytokine levels were measured in serum samples from 20 hospitalized patients with SAB, 20 hospitalized patients with GNB, 10 non-infected hospitalized patients, and 10 community controls. C5a levels were significantly higher in patients with SAB as compared to patients with GNB. Low C4 and C3 levels were associated with septic shock and 30-day mortality in patients with GNB, and elevated C3 was associated with a desirable outcome defined as absence of (1) septic shock, (2) acute renal failure, and (3) death within 30 days of bacteremia. Low levels of C9 were associated with septic shock in patients with GNB but not SAB. Elevated IL-10 was associated with increased 30-day mortality in patients with SAB. Complement profiles differ in patients with SAB and those with GNB. Measurement of IL-10 in patients with SAB and of C4, C3, and C9 in patients with GNB may help to identify those at higher risk for poor outcomes. Keywords Complement . Staphylococcus aureus bacteremia . Gram-negative bacteremia . Cytokine . Sepsis . Septic shock
Introduction Bloodstream infections are associated with substantial morbidity and mortality worldwide [1, 2]. It is estimated that approximately 2 million episodes and 250,000 deaths from bloodstream infections occur annually in Europe and North America combined [2]. A consistent predictor of mortality for patients with S. aureus bacteremia (SAB) [3, 4] and Gram-negative bacteremia Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10096-020-03955-z) contains supplementary material, which is available to authorized users. * Emily M. Eichenberger [email protected] 1
Present address: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, NC 27710, USA
2
Duke Global Health Institute, Duke University, Durham, NC, USA
3
Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA
(GNB) is the presence of septic shock [5]. Septic shock is thought to involve a dysregulated immune response to infection, the mechanisms of which are incompletely understood. The complement system is a critical component of innate immunity and has been implicated as a significant player in the pathogenesis of sepsis and septic shock [6–8]. Acute phase cytokine expression has also been
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