Adjunctive dabigatran therapy improves outcome of experimental left-sided Staphylococcus aureus endocarditis.
Animals
Anti-Bacterial Agents
/ pharmacology
Antithrombins
/ pharmacology
Aortic Valve
/ drug effects
Bacterial Load
/ drug effects
Chemotherapy, Adjuvant
Dabigatran
/ pharmacology
Disease Models, Animal
Drug Therapy, Combination
Endocarditis, Bacterial
/ drug therapy
Gentamicins
/ pharmacology
Humans
Male
Random Allocation
Rats, Wistar
Staphylococcal Infections
/ drug therapy
Staphylococcus aureus
/ drug effects
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
08
01
2019
accepted:
29
03
2019
entrez:
20
4
2019
pubmed:
20
4
2019
medline:
14
1
2020
Statut:
epublish
Résumé
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. 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. 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. Adjunctive dabigatran reduced the vegetation size, bacterial load, and inflammation in experimental S. aureus IE.
Sections du résumé
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.
Identifiants
pubmed: 31002679
doi: 10.1371/journal.pone.0215333
pii: PONE-D-19-00686
pmc: PMC6474597
doi:
Substances chimiques
Anti-Bacterial Agents
0
Antithrombins
0
Gentamicins
0
Dabigatran
I0VM4M70GC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0215333Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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