Abstract
BackgroundStaphylococcus aureus is the most frequent and fatal cause of left-sided infective endocarditis (IE). New treatment strategies are needed to improve the outcome. S. aureus coagulase promotes clot and fibrin formation. We hypothesized that dabigatran, could reduce valve vegetations and inflammation in S. aureus IE.MethodsWe used a rat model of severe aortic valve S. aureus IE. All infected animals were randomized to receive adjunctive dabigatran (10 mg/kg b.i.d., n = 12) or saline (controls, n = 11) in combination with gentamicin. Valve vegetation size, bacterial load, cytokine, cell integrins expression and peripheral platelets and neutrophils were assessed 3 days post-infection.ResultsAdjunctive dabigatran treatment significantly reduced valve vegetation size compared to controls (p< 0.0001). A significant reduction of the bacterial load in aortic valves was seen in dabigatran group compared to controls (p = 0.02), as well as expression of key pro-inflammatory markers keratinocyte-derived chemokine, IL-6, ICAM-1, TIMP-1, L-selectin (p< 0.04). Moreover, the dabigatran group had a 2.5-fold increase of circulating platelets compared to controls and a higher expression of functional and activated platelets (CD62p+) unbound to neutrophils.ConclusionAdjunctive dabigatran reduced the vegetation size, bacterial load, and inflammation in experimental S. aureus IE.
Highlights
Staphylococcus aureus is the most frequent cause of infectious endocarditis (IE) [1] and is associated with serious clinical manifestations and fatal course in two out of five patients [2] despite appropriate antibiotic therapy, appropriate management of sepsis and intensive care treatment often combined with cardiac valve surgery
Adjunctive dabigatran treatment significantly reduced valve vegetation size compared to controls (p< 0.0001)
A significant reduction of the bacterial load in aortic valves was seen in dabigatran group compared to controls (p = 0.02), as well as expression of key pro-inflammatory markers keratinocyte-derived chemokine, IL-6, ICAM-1, tissue metallopeptidase inhibitor 1 (TIMP-1), L-selectin (p< 0.04)
Summary
Staphylococcus aureus is the most frequent cause of infectious endocarditis (IE) [1] and is associated with serious clinical manifestations and fatal course in two out of five patients [2] despite appropriate antibiotic therapy, appropriate management of sepsis and intensive care treatment often combined with cardiac valve surgery. Platelets are known for the ability to trigger neutrophil degranulation, referred to as neutrophil extracellular traps (NETs) [6,11,12,13]. This fundamental innate immune effector function of neutrophils [14] is essential in endovascular infections, but may cause tissue injury [15,16] and promote additional intravascular thrombosis [17,18,19]. NETs can promote thrombin generation both by platelet-dependent and -independent mechanisms [20] and trigger an exaggerated host response and enhancement of biofilm formation [21]. Could reduce valve vegetations and inflammation in S. aureus IE.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
