Antibiotic effect of ticagrelor

Ticagrelor is a reversible platelet adenosine diphosphate P2Y₁₂ receptor (P2Y₁₂) inhibitor and is quite effective as an antiplatelet agent. New research suggests an antibiotic effect for ticagrelor and the researchers suggest that further research may lead to development of a new class of antibiotics [1]. In fact there is a global need for new antibiotics, which are conspicuous by their absence in the current scenario of multidrug resistant organisms. The study published as a Research Letter in JAMA Cardiology reports on the ‘Antibacterial Activity of Ticagrelor in Conventional Antiplatelet Dosages Against Antibiotic-Resistant Gram-Positive Bacteria’.

Initial suggestion came from a post hoc analysis of PLAT trial [2] which showed that the mortality was lower following pulmonary adverse events and sepsis in those receiving ticagrelor in comparison with clopidogrel [3]. Later the Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor (XANTHIPPE) study, showed that ticagrelor reduces thrombo-inflammatory markers in patients with pneumonia [4].

Lancellotti P et al [1] tested ticagrelor and its major metabolites against multiple bacteria in time-kill assays. Bactericidal activity was demonstrated against all gram positive bacteria tested, including drug resistant strains of methicillin resistant staphylococcus aureus and vancomycin resistant enterococci. It had also effect on biofilm formation by the bacteria. Yet it may be noted that the concentrations required for this activity was not achieved in humans receiving standard doses of ticagrelor. But the researchers suggest the need for further studies with derivatives of ticagrelor with less of antiplatelet activity to prevent bleeding and more of antibacterial activity. They hope that development of such a derivative might in future give us a new generation of antibiotics.

References

1. Lancellotti P, Musumeci L, Jacques N, Servais L, Goffin E, Pirotte B, Oury C. Antibacterial Activity of Ticagrelor in Conventional Antiplatelet Dosages Against Antibiotic-Resistant Gram-Positive Bacteria. JAMA Cardiol. 2019 May 8. doi: 10.1001/jamacardio.2019.1189. [Epub ahead of print]
2. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057.
3. Storey RF, James SK, Siegbahn A, Varenhorst C, Held C, Ycas J, Husted SE, Cannon CP, Becker RC, Steg PG, Åsenblad N, Wallentin L. Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study. Platelets. 2014;25(7):517-25.
4. Sexton TR, Zhang G, Macaulay TE, Callahan LA, Charnigo R, Vsevolozhskaya OA, Li Z, Smyth S. Ticagrelor Reduces Thromboinflammatory Markers in Patients With Pneumonia. JACC Basic Transl Sci. 2018 Aug 28;3(4):435-449.