What Is Sepsis, Who Gets It, How, and Why? The Keys to Unlocking Precision Medicine in Sepsis

Due to its nonspecific clinical criteria, sepsis is clinically, microbiologically, pathophysiologically and immunologically highly heterogeneous. Consequently, despite hundreds of clinical trials, no host-targeted therapy has been shown to be ubiquitously efficacious, leading investigators to pursue more precision-based approaches for enriching sepsis populations through the identification of subgroups or phenotypes. Here, we review the myriad domains in which heterogeneity is observed in sepsis and the challenges and opportunities they offer to improve outcomes. We review current strategies used by investigators leveraging novel biological measurements and/or computational algorithms to identify more homogeneous subgroups either based on pathogen or host characteristics or both. Finally, we review some of the most promising recent advances that seek to bring these complex and innovative discoveries to the bedside to facilitate precision medicine in sepsis.