Prophylaxis of Experimental Endocarditis With Antiplatelet and Antithrombin Agents: A Role for Long-term Prevention of Infective Endocarditis in Humans?

Background. Infective endocarditis (IE) mostly occurs after spontaneous low-grade bacteremia. Thus, IE cannot be prevented by circumstantial antibiotic prophylaxis. Platelet activation following bacterial-fibrinogen interaction or thrombin-mediated fibrinogen-fibrin polymerization is a critical step...

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Bibliographic Details
Published in:The Journal of infectious diseases 2015-01, Vol.211 (1), p.72-79
Main Authors: Veloso, Tiago Rafael, Que, Yok-Ai, Chaouch, Aziz, Giddey, Marlyse, Vouillamoz, Jacques, Rousson, Valentin, Moreillon, Philippe, Entenza, José Manuel
Format: Article
Language:English
Subjects:
Animals
Antibiotic Prophylaxis - methods
Bacteremia - drug therapy
Bacteremia - microbiology
BACTERIA
Disease Models, Animal
Endocarditis, Bacterial - drug therapy
Endocarditis, Bacterial - microbiology
Fibrinolytic Agents - pharmacology
Humans
Platelet Aggregation Inhibitors - pharmacology
Rats
Staphylococcal Infections - drug therapy
Staphylococcal Infections - microbiology
Staphylococcus aureus - drug effects
Streptococcus gordonii - drug effects
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Summary:Background. Infective endocarditis (IE) mostly occurs after spontaneous low-grade bacteremia. Thus, IE cannot be prevented by circumstantial antibiotic prophylaxis. Platelet activation following bacterial-fibrinogen interaction or thrombin-mediated fibrinogen-fibrin polymerization is a critical step in vegetation formation. We tested the efficacy of antiplatelet and antithrombin to prevent experimental IE. Methods. A rat model of experimental IE following prolonged low-grade bacteremia mimicking smoldering bacteremia in humans was used. Prophylaxis with antiplatelets (aspirin, ticlopidine [alone or in combination], eptifibatide, or abciximab) or anticoagulants (antithrombin dabigatran etexilate or anti-vitamin K acenocoumarol) was started 2 days before inoculation with Streptococcus gordonii or Staphylococcus aureus. Valve infection was assessed 24 hours later. Results. Aspirin plus ticlopidine, as well as abciximab, protected 45%-88% of animals against S. gordonii and S. aureus IE (P < .05). Dabigatran etexilate protected 75% of rats against IE due to S. aureus (P < .005) but failed to protect against S. gordonii (< 30% protection). Acenocoumarol was ineffective. Conclusions. Antiplatelet and direct antithrombin agents may be useful in the prophylaxis of IE in humans. In particular, the potential dual benefit of dabigatran etexilate might be reconsidered for patients with prosthetic valves, who require life-long anticoagulation and in whom S. aureus IE is associated with high mortality.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiu426