title: Prophylaxis of experimental endocarditis with antiplatelet and antithrombin agents: a role for long-term prevention of infective endocarditis in humans?
abstract: 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.
authors.affiliation: Department of Fundamental Microbiology.
authors.forename: Tiago Rafael
authors.initials: TR
authors.lastname: Veloso
authors.affiliation: Department of Intensive Care Medicine.
authors.forename: Yok-Ai
authors.initials: YA
authors.lastname: Que
authors.affiliation: Statistical Unit, Institute for Social and Preventive Medicine, University of Lausanne, Switzerland.
authors.forename: Aziz
authors.initials: A
authors.lastname: Chaouch
authors.affiliation: Department of Fundamental Microbiology.
authors.forename: Marlyse
authors.initials: M
authors.lastname: Giddey
authors.affiliation: Department of Fundamental Microbiology.
authors.forename: Jacques
authors.initials: J
authors.lastname: Vouillamoz
authors.affiliation: Statistical Unit, Institute for Social and Preventive Medicine, University of Lausanne, Switzerland.
authors.forename: Valentin
authors.initials: V
authors.lastname: Rousson
authors.affiliation: Department of Fundamental Microbiology.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreillon
authors.affiliation: Department of Fundamental Microbiology.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Entenza
mesh_terms: D000818:Animals; D019072:Antibiotic Prophylaxis / Q000379:methods; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D054773:Streptococcus gordonii / Q000187:drug effects
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors
keywords: Staphylococcus aureus; Streptococcus gordonii; anticoagulants; antiplatelets; experimental endocarditis; prophylaxis