Sepsis future or investigational therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Parth Vikram Singh, MBBS[2]

Synonyms and keywords: sepsis syndrome; septic shock; septicemia

Emerging Areas of Research

There is an increasing focus on the heterogeneity of sepsis, with ongoing work in several domains:

• Endotypes and subphenotypes: Distinct biological profiles, including transcriptomic and metabolic traits, are being investigated to classify patients into clinically meaningful subgroups.
• Predictive analytics: Machine learning models, such as those described by Pirracchio et al. (2020), are being evaluated for their ability to anticipate individual treatment responses and guide precision therapy.
• Targeted therapies for host dysregulation: Therapeutic development remains limited in areas such as vascular permeability, complement pathway modulation, and restoration of immune function, highlighting current gaps in treatment.
• Global Context: Most randomized controlled trials of sepsis management have been conducted in high-income countries (HICs). Data from low- and middle-income countries (LMICs) suggest that responses to treatment may differ due to variations in available resources, baseline comorbidities, and pathogen prevalence. For example, the SSSP-2 trial conducted in Zambia highlights the need for context-specific strategies in resource-limited settings.