2026/03/15 by Georgios D. Kitsios, Rebecca M. Baron · 1 voice
Immunology and Microbiology · Medicine · #Immune Response and Inflammation #Neonatal and Maternal Infections #Sepsis Diagnosis and Treatment
paper · doi:10.1172/jci203658
openalex publication_date 2026/03/15 · openalex created_date 2026/03/16 · openalex updated_date 2026/07/12
For over a decade, sepsis phenotyping has identified hyperinflammatory and hypoinflammatory subphenotypes using host biomarkers and clinical variables, without factoring in contributions from infectious insults across patients. In this issue, Chanderraj and colleagues challenge this host-centric paradigm by demonstrating that pathogen characteristics independently contribute to sepsis subphenotypes. They reported that Enterobacterales infections, particularly Escherichia coli, strongly associated with hyperinflammatory subphenotypes, independent of illness severity. Bacterial burden, anatomic barrier breach, and circulating pathogen-associated molecular patterns influence phenotypic classification, with implications extending to culture-negative sepsis. Animal models supported causality, while reanalysis of an observational cohort and a clinical trial revealed that lactate clearance's prognostic value and therapeutic effects of endotoxin removal with polymyxin B hemoadsorption vary by subphenotype and pathogen. These findings lay groundwork for integrative host-pathogen phenotyping; for precision medicine in critical illness, we must know not only who is sick, but what made them sick, and how the two interact.