Remarkable activity of Ticagrelor against infective endocarditis
In 2019, the team of Profs Cécile Oury and Patrizio Lancellotti, researchers at GIGA - University of Liège, discovered that the drug used to prevent cardiovascular disease, ticagrelor also possessed antibacterial properties against Gram-positive bacteria, including the most resistant. In a new study published in the prestigious journal JACC, the same team describes the remarkable activity of the drug against infective endocarditis.
nfective endocarditis remains a deadly disease with a mortality rate of approximately 20-40%. The major causative organisms of IE are Gram-positive bacteria, with S. aureus being the most common and virulent. Current antibiotics used to treat IE are not very effective, especially when multidrug-resistant organisms cause the disease. It is, therefore, essential to find new ways to prevent this disease adequately.
The Heart Lab team's results show a unique efficacy of the anti-platelet drug ticagrelor in mice against the development of IE caused by a clinical isolate of S. aureus.
In experiments performed ex vivo in the presence of human blood, we demonstrate that a conventional dose of ticagrelor has antivirulence activity against S. aureus. Ticagrelor renders the bacterium less virulent by inducing major changes in its quorum sensing system and in its ability to adhere to activated endothelial cells. This represents a unique mode of action never seen with available antibiotics.
Clinical implications: these results should motivate new initiatives to design randomized clinical trials to study the protective effect of adjuvant treatment with ticagrelor against Gram-positive bacterial infections after, for example, prosthetic heart valve replacement.
As an antivirulence agent, ticagrelor would probably not impose high selective pressure on bacteria, limiting the development of resistance and the spread of virulence genes.
Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent Staphylococcus aureus in Mice
Cécile Oury, Severien Meyers, Nicolas Jacques, Kirsten Leeten, Zheshen Jiang, Lucia Musumeci, Marleen Lox, Margaux Debuisson, Eric Goffin, Bernard Pirotte, Philippe Delvenne, Alain Nchimi, Cédric Hubert, Mélanie Heptia, Philippe Hubert, Marijke J.E. Kuijpers, Thomas Vanassche, Kimberly Martinod, Peter Verhamme, Patrizio Lancellotti