Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Adjunctive dabigatran therapy improves outcome of experimental left-sided Staphylococcus aureus endocarditis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{d2edca1cd0be45da812e0b9194b4d3b2,
title = "Adjunctive dabigatran therapy improves outcome of experimental left-sided Staphylococcus aureus endocarditis",
abstract = "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.",
author = "Lerche, {Christian J} and Christophersen, {Lars J} and Goetze, {Jens Peter} and Nielsen, {Pia R} and Kim Thomsen and Christian Enevold and Niels H{\o}iby and Jensen, {Peter {\O}} and Henning Bundgaard and Claus Moser",
year = "2019",
doi = "10.1371/journal.pone.0215333",
language = "English",
volume = "14",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

RIS

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

VL - 14

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 4

M1 - e0215333

ER -

ID: 57238632