ticagrelor and Cross-Infection

The antiplatelet agent ticagrelor has recently been found to have bactericidal activity, demonstrated in vitro and in an in vivo mouse model, which warrants further clinical investigations. The aim of this study was to evaluate infectious complications after coronary artery bypass grafting in patients pre-operatively treated with ticagrelor or clopidogrel. In a multi-centre trial, all adult patients who were pre-operatively treated with ticagrelor or clopidogrel prior to isolated primary coronary artery bypass grafting were eligible. Propensity score matching was used. Outcome measures were any sternal wound infection, deep sternal wound infection, and any in-hospital use of postoperative antibiotics. Of 2311 patients who were included, 1293 (55.9%) received clopidogrel and 1018 (44.1%) ticagrelor pre-operatively. In both overall and propensity score matched analyses, ticagrelor was associated with a similar incidence of infectious complications compared to clopidogrel. Our findings do not support a clinically relevant bactericidal effect of ticagrelor in patients undergoing coronary artery bypass grafting.

Topics: Aged; Aged, 80 and over; Clopidogrel; Coronary Artery Bypass; Cross Infection; Europe; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Preoperative Care; Propensity Score; Ticagrelor

Drug resistance in Clostridioides difficile becomes a public health concern worldwide, especially as the hypervirulent strains show decreased susceptibility to the first-line antibiotics for C. difficile treatment. Therefore, the simultaneous discovery and development of new compounds to fight this pathogen are urgently needed. In order to determinate new drugs active against C. difficile, we identified ticagrelor, utilized for the prevention of thrombotic events, as exhibiting potent growth-inhibitory activity against C. difficile. Whole-cell growth inhibition assays were performed and compared to vancomycin and metronidazole, followed by determining time-kill kinetics against C. difficile. Activities against biofilm formation and spore germination were also evaluated. Leakage analyses and electron microscopy were applied to confirm the disruption of membrane structure. Finally, ticagrelor's ability to synergize with vancomycin and metronidazole was determined using checkerboard assays. Our data showed that ticagrelor exerted activity with a MIC range of 20-40 µg/mL against C. difficile. This compound also exhibited an inhibitory effect on biofilm formation and spore germination. Additionally, ticagrelor did not interact with vancomycin nor metronidazole. Our findings revealed for the first time that ticagrelor could be further developed as a new antimicrobial agent for fighting against C. difficile.

Topics: Anti-Bacterial Agents; Biofilms; Cell Membrane; Clostridioides difficile; Clostridium Infections; Cross Infection; Drug Evaluation, Preclinical; Drug Repositioning; Drug Resistance, Bacterial; Drug Synergism; Humans; Metronidazole; Microbial Sensitivity Tests; Microscopy, Electron; Spores, Bacterial; Ticagrelor; Vancomycin