Addition of ticagrelor (TICA) to antimicrobial therapy provided immediate clinical and microbiological success in a complex case of aortic plaque rupture with septic thrombus, multiple septic emboli, and refractory methicillin-susceptible S aureus (MSSA) bacteremia, according to a case presented at IDWeek, held virtually from October 21 to 25.

Investigators previously identified that the alpha-toxin-induced, platelet-clearing activity of S aureus is blocked by TICA in animal models. They tested the antibiotic susceptibility of an MSSA strain from a patient treated with TICA for refractory bacteremia. Testing was done by MIC and checkerboard assays using TICA, ertapenem, cefazolin, or nafcillin alone vs ertapenem plus cefazolin with or without ticagrelor. They also performed killing assays with human platelets with or without TICA against S aureus.

Adding ticagrelor cleared bacteremia secondary to a septic aortic thrombus (>4mm), with multiple secondary pyogenic foci refractory to standard CZ and subsequent salvage CZ+ETP for 5 days, within 24 hours. Thrombocytopenia resolved concurrently but rebounded on day 12 after TICA was discontinued. Thrombocytopenia was resolved after restarting TICA.

TICA alone lacked in-vitro activity against S aureus, and it was not synergistic with ETP+CZ. However, addition of a physiological achievable concentration of TICA dramatically sensitized S aureus to in-vitro human platelet killing (P <.001), the investigators noted.


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According to investigators, “The profound therapeutic effect of TICA in vivo was corroborated by the enhanced staphylocidal activity of human platelets in vitro in the presence of physiological concentrations of the antiplatelet agent.” Based on this finding, they believe TICA warrants further study as an adjunctive treatment of refractory S aureus bacteremia due to a primary endovascular focus when thrombocytopenia is present.

Disclosure: A study author declared affiliations with pharmaceutical industries. Please see the original reference for a full list of author’s disclosures.

Reference

Ulloa ER, Uchiyama S, Nizet V, Sakoulas G. Ticagrelor aids platelet-mediated clearance in a refractory staphylococcus aureus endovascular infection with septic emboli. Presented at: IDWeek 2020; October 21-25, 2020. Poster 255.