Lancellotti P, et al. - Researchers examined ticagrelor for its bactericidal activity against antibiotic-resistant gram-positive bacteria that pose a threat to human health. They synthesized and tested ticagrelor and its major metabolites (M5 AR-C133913, M7, M8 AR-C124910)5 in time-kill assays against gram-positive methicillin-resistant Staphylococcus epidermidis RP62A (MRSE) (ATCC 35984); methicillin-sensitive Staphylococcus aureus (MSSA) (ATCC 25904, ATCC 6538); glycopeptide intermediate S aureus (GISA) Mu-50 (ATCC 700699); methicillin-resistant S aureus (MRSA) (ATCC BAA-1556); Enterococcus faecalis (ATCC 29212); vancomycin-resistant E faecalis (VRE) (ATCC BAA-2365); and Streptococcus agalactiae (ATCC 12386) and against gram-negative Escherichia coli (ATCC 8739) and Pseudomonas aeruginosa (PAK laboratory strain). Ticagrelor and AR-C124910 showed bactericidal activity against all gram-positive strains tested, including drug-resistant strains GISA, MRSE, MRSA, and VRE. As per findings, researchers suggest that in patients receiving typical dosages for treating cardiovascular disease, bactericidal concentrations are not reached systemically (ticagrelor C_max = 1.2 μg/mL after one 180-mg loading dose and 0.75 μg/mL at 90 mg twice daily steady state), however, local, possibly platelet-driven, drug accumulation may still lead to antibacterial activity at infection sites. The reduced infection-related death with ticagrelor seen in the PLATO trial could be mechanistically explained via these findings. The improvement in lung function in patients with pneumonia who took ticagrelor in the XANTHIPPE study could also be explained by the findings.