Personalized Therapeutic Strategies in Sepsis and Septic Shock: Integrating Biomarkers, Immune Phenotypes, and Targeted Interventions

Abstract

Sepsis remains a major global health challenge and is characterized by a highly heterogeneous and dysregulated host response to infection that can lead to life-threatening organ dysfunction and septic shock. Despite advances in critical care management, clinical outcomes remain poor in a
significant proportion of patients, largely due to the biological and clinical heterogeneity of the syndrome. In recent years, increasing attention has
been directed toward precision medicine approaches aimed at improving patient stratification and guiding individualized therapeutic strategies. This
review summarizes current evidence on the classification of sepsis into distinct phenotypes and endotypes based on clinical characteristics, immune response profiles, and biomarker signatures. Particular emphasis is placed on the spectrum of immune dysregulation ranging from hyperinflammatory states to immunosuppressive phenotypes and the implications of these patterns for targeted therapeutic interventions. Emerging rescue strategies for refractory septic shock, including extracorporeal life support modalities such as extracorporeal membrane oxygenation, hemoadsorption techniques, immunomodulatory therapies, and other phenotype-directed interventions, are also discussed. In addition, advances in biomarker-guided stratification and translational insights into the molecular mechanisms underlying sepsis pathophysiology are highlighted. Collectively, these developments underscore
the potential of precision medicine frameworks to improve the identification of clinically relevant patient subgroups and to optimize therapeutic decisionmaking. Future research focusing on validated biomarkers, robust phenotyping strategies, and well-designed clinical trials will be essential to translate these concepts into improved clinical outcomes for patients with sepsis and septic shock.