ticagrelor and Bacteremia

Staphylococcus aureus bacteremia (SAB) remains a clinically challenging infection despite extensive investigation. Repurposing medications approved for other indications is appealing as clinical safety profiles have already been established. Ticagrelor, a reversible adenosine diphosphate receptor antagonist that prevents platelet aggregation, is indicated for patients suffering from acute coronary syndrome (ACS). However, some clinical data suggest that patients treated with ticagrelor are less likely to have poor outcomes due to S. aureus infection. There are several potential mechanisms by which ticagrelor may affect S. aureus virulence. These include direct antibacterial activity, up-regulation of the innate immune system through boosting platelet-mediated S. aureus killing, and prevention of S. aureus adhesion to host tissues. In this Pearl, we review the clinical data surrounding ticagrelor and infection as well as explore the evidence surrounding these proposed mechanisms of action. While more evidence is needed before antiplatelet medications formally become part of the arsenal against S. aureus infection, these potential mechanisms represent exciting pathways to target in the host/pathogen interface.

Topics: Bacteremia; Blood Platelets; Host-Pathogen Interactions; Humans; Immunity, Innate; Platelet Aggregation Inhibitors; Staphylococcal Infections; Staphylococcus aureus; Ticagrelor

Ticagrelor may improve the outcomes in Staphylococcus aureus bacteraemia (SAB). However, treatment outcome data for these patients remain limited. The primary objective of this study was to characterize the outcomes of patients with SAB who received ticagrelor compared with a cohort who received clopidogrel.. This was a retrospective, nationwide propensity-matched analysis of patients with SAB who were prescribed ticagrelor or clopidogrel concomitantly with antistaphylococcal therapy. The primary outcome was the comparative all-cause 30-day mortality rate between propensity-matched groups.. In total, 1509 patients were prescribed concomitantly with ticagrelor or clopidogrel during treatment of S. aureus bacteraemia; of these, 194 patients were excluded from this study due to an inadequate number of antiplatelet doses within the first week of therapy (n=171) or non-admission to hospital (n=23). Of the remaining 1315 patients, 74 patients received ticagrelor and 1241 patients received clopidogrel. There was no significant difference in all-cause 30-day mortality between the groups [6/74 (8.1%) in the ticagrelor group vs 10/74 (13.5%) in the clopidogrel group; P=0.29]. Multi-variate logistic regression demonstrated that elevated aspartate aminotransferase, systolic blood pressure <90 mmHg, elevated serum creatinine and neurological comorbidity were independently associated with all-cause 30-day mortality.. This study found no difference in all-cause 30-day mortality between the two groups, although overall mortality appeared to be lower compared with other reports. Randomized controlled trials of P2Y12 inhibitors as adjunctive agents to antibiotic therapy for the treatment of serious S. aureus infections are warranted.

Topics: Bacteremia; Clopidogrel; Humans; Platelet Aggregation Inhibitors; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Ticagrelor; Treatment Outcome

To investigate the 1-year risks of Staphylococcus aureus bacteraemia (SAB), sepsis, and pneumonia in patients who underwent percutaneous coronary intervention and were treated with ticagrelor vs. clopidogrel.. In this nationwide observational cohort study, 26 606 patients who underwent urgent or emergent percutaneous coronary intervention (January 2011-December 2017) and initiated treatment with ticagrelor [N = 20 073 (75.5%); median age 64 years (25th-75th percentile 55-72 years); 74.8% men] or clopidogrel [N = 6533 (24.5%); median age 68 years (25th-75th percentile 58-77 years); 70.2% men] were identified using Danish nationwide registries. The 1-year standardized absolute risks of outcomes was calculated based on cause-specific Cox regression models, and average treatment effects between treatment groups were obtained as standardized differences in absolute 1-year risks. The absolute 1-year risk of SAB was 0.10% [95% confidence interval (CI), 0.05-0.15%] in the ticagrelor group and 0.29% (95% CI, 0.17-0.42%) in the clopidogrel group. Compared with clopidogrel, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of SAB [absolute risk difference -0.19% (95% CI, -0.32% to -0.05%), P value 0.006]. Likewise, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of sepsis [0.99% (95% CI, 0.83-1.14%) vs. 1.49% (95% CI, 1.17-1.80%); absolute risk difference -0.50% (95% CI, -0.86% to -0.14%), P value 0.007] and pneumonia [3.13% (95% CI, 2.86-3.39%) vs. 4.56% (95% CI, 4.03-5.08%); absolute risk difference -1.43% (95% CI, -2.03% to -0.82%), P value < 0.001] compared with clopidogrel.. Treatment with ticagrelor was associated with a significantly lower 1-year risk of SAB, sepsis, and pneumonia compared with clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Bacteremia; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Staphylococcal Infections; Staphylococcus aureus; Ticagrelor; Treatment Outcome

Platelets are a critical immune defense against Staphylococcus aureus bloodstream infections. Staphylococcus aureus α-toxin is a virulence factor that decreases platelet viability and accelerates platelet clearance. It has been shown that ticagrelor blocks α-toxin-mediated platelet injury and resulting thrombocytopenia, protecting mice in a lethal S. aureus sepsis model. We now present the use of ticagrelor as adjunctive therapy in a patient with a S. aureus endovascular infection and thrombocytopenia, associated with restoration of platelet count and bacteremia clearance. Ticagrelor enhanced platelet killing of the S. aureus bloodstream isolate from the treated patient in vitro.

Topics: Animals; Bacteremia; Blood Platelets; Humans; Immunity, Innate; Mice; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Staphylococcal Infections; Staphylococcus aureus; Ticagrelor