Rationalizing Heterogeneity in Staphylococcus aureus Bacteremia: Current Progress and Future Goals

Clinical and biological heterogeneity in Staphylococcus aureus bacteraemia (SAB) continue to pose significant challenges for the clinical management of individual patients and for research efforts. We contend that investigating SAB as a single disease is impeding the identification of beneficial therapeutic approaches. Recently, three data-driven approaches for patient stratification in SAB have been reported, using routinely available data to identify clinically distinct subphenotypes with differences in mortality, microbiologic outcomes, and response to adjunctive antimicrobial therapies (the Swets et al, FEN-AUREUS, and MRSA-GEIRAS-SEIMC studies). In this review, we compare the methodologies and findings from these studies, discuss their limitations, and identify goals for future research in this space. We expect that transformative advances in SAB management will only be achieved by addressing clinical and biological heterogeneity, enabling progress from observable clinical subphenotypes to mechanism-based endotypes defined by treatable traits.