Adjunctive dabigatran therapy improves outcome of experimental left-sided Staphylococcus aureus endocarditis
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Adjunctive dabigatran therapy improves outcome of experimental left-sided Staphylococcus aureus endocarditis. / Lerche, Christian J; Christophersen, Lars J; Goetze, Jens Peter; Nielsen, Pia R; Thomsen, Kim; Enevold, Christian; Høiby, Niels; Jensen, Peter Ø; Bundgaard, Henning; Moser, Claus.
In: PLoS ONE, Vol. 14, No. 4, e0215333, 2019.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Adjunctive dabigatran therapy improves outcome of experimental left-sided Staphylococcus aureus endocarditis
AU - Lerche, Christian J
AU - Christophersen, Lars J
AU - Goetze, Jens Peter
AU - Nielsen, Pia R
AU - Thomsen, Kim
AU - Enevold, Christian
AU - Høiby, Niels
AU - Jensen, Peter Ø
AU - Bundgaard, Henning
AU - Moser, Claus
PY - 2019
Y1 - 2019
N2 - BACKGROUND: Staphylococcus 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.METHODS: We 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.RESULTS: 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, 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.CONCLUSION: Adjunctive dabigatran reduced the vegetation size, bacterial load, and inflammation in experimental S. aureus IE.
AB - BACKGROUND: Staphylococcus 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.METHODS: We 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.RESULTS: 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, 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.CONCLUSION: Adjunctive dabigatran reduced the vegetation size, bacterial load, and inflammation in experimental S. aureus IE.
U2 - 10.1371/journal.pone.0215333
DO - 10.1371/journal.pone.0215333
M3 - Journal article
C2 - 31002679
VL - 14
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 4
M1 - e0215333
ER -
ID: 224598460