Antibacterial Activity of Ticagrelor in Conventional Antiplatelet Dosages Against Antibiotic-Resistant Gram-Positive Bacteria

Abstract

This study uses in vitro assays and a mouse model to investigate antibacterial properties of ticagrelor to follow up findings from 2 clinical trials that showed patients taking ticagrelor for cardiovascular disease had a lower risk of infection-related death and improved lung function compared with patients treated with clopidogrel.

Figure 1.. In Vitro Characterization of Bactericidal and Anti-Biofilm Activity of Ticagrelor on MRSA, MRSE, and VRE

A-C, Time-kill curves with ticagrelor (20 μg/mL for MRSA and VRE; 45 μg/mL for MRSE), vancomycin (10 μg/mL), daptomycin (20 μg/mL for MRSA and VRE; 10 μg/mL for MRSE) or vehicle (1% DMSO). D-F, Mean biofilm biomass. Error bars indicate SD. CFU indicates colony-forming units; DMSO, dimethylsulfoxide, MRSA, methicillin-resistant Staphylococcus aureus; MRSE, methicillin-resistant Staphylococcus epidermidis; and VRE, vancomycin-resistant Enterococcus faecalis. ^aP < .05. ^bP < .01. ^cP < .001.

Figure 2.. In Vivo Bactericidal Activity of Ticagrelor in a Mouse Subcutaneous Foreign-Body Staphylococcus aureus Infection Model

A, Representative images of implanted mice before treatment and 24 hours after treatment with ticagrelor or vehicle. B, Mean values of bioluminescent signals. Error bars indicate SD. C, Skin sections (Gram stain [Sigma-Aldrich], original magnification ×6.5). Blue areas represent bacteria. Bars = 50 μm. p/s Indicates photon per signal.