Published on Wed Jul 28 2021

Increased risk of thrombocytopenia and death in patients with bacteremia caused by high alpha toxin-producing methicillin-resistant Staphylococcus aureus.

Alhurayri, F., Porter, E., Douglas-Louis, R., Minejima, E., Bubeck Wardenburg, J., Wong-Beringer, A.

Alpha toxin (Hla) is a major virulence factor of Staphylococcus aureus that targets platelets. Clinical data on Hla pathogenesis in bacteremia (SAB) is limited. We examined the link between in vitro Hla activity and outcome.

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Abstract

Background: Alpha toxin (Hla) is a major virulence factor of Staphylococcus aureus that targets platelets but clinical data on Hla pathogenesis in bacteremia (SAB) is limited. Objective: We examined the link between in vitro Hla activity and outcome. Methods: Study isolates obtained from 100 patients with SAB (50 survivors; 50 non-survivors) were assessed for in vitro Hla production and activity by Western immunoblotting and hemolysis assay, respectively. Relevant demographics, laboratory and clinical data were extracted from patients' medical records to correlate Hla activity of the infecting isolates with outcome. Results: Hla production strongly correlated with hemolytic activity (rs=0.93) in vitro. A trend towards higher hemolytic activity was observed for MRSA compared to MSSA and with high-risk source infection. Significantly higher hemolytic activity was noted for MRSA strains isolated from patients who developed thrombocytopenia (median 52.48 vs 16.55 HU/ml in normal platelet count, p=0.012) and from non survivors (median 30.96 vs 14.87 HU/ml in survivors, p= 0.014) but hemolytic activity of MSSA strains did not differ between patient groups. Conclusions: In vitro Hla activity of S. aureus strains obtained from patients with bacteremia may be used to predict risk for thrombocytopenia and death which supports bedside phenotyping and therapeutic targeting in the future.