Weekly Sepsis Research Analysis
This week’s sepsis literature converged on three high-impact advances: (1) a PROSPERO-registered meta-analysis showing adjunctive corticosteroids reduce short-term mortality and need for invasive ventilation in hospitalized non-viral CAP, (2) laboratory workflow innovations enabling same-day disk diffusion AST directly from positive blood cultures (eQUANT) that can shorten time-to-targeted therapy, and (3) mechanistic preclinical work that repurposes an FDA-approved FXR agonist (obeticholic acid
Summary
This week’s sepsis literature converged on three high-impact advances: (1) a PROSPERO-registered meta-analysis showing adjunctive corticosteroids reduce short-term mortality and need for invasive ventilation in hospitalized non-viral CAP, (2) laboratory workflow innovations enabling same-day disk diffusion AST directly from positive blood cultures (eQUANT) that can shorten time-to-targeted therapy, and (3) mechanistic preclinical work that repurposes an FDA-approved FXR agonist (obeticholic acid) to enhance neonatal MDSC function and protect against neonatal sepsis. Across the week, complementary papers advanced rapid diagnostics, immune-targeted interventions, and practical prognostic/predictive tools with clear implications for trial design and bedside care.
Selected Articles
1. Corticosteroids for adult patients hospitalised with non-viral community-acquired pneumonia: a systematic review and meta-analysis.
PROSPERO-registered meta-analysis of 30 RCTs (n=7,519) found that adjunctive corticosteroids probably reduce 28–30-day mortality (RR 0.82) and substantially reduce need for invasive mechanical ventilation (RR 0.63) in hospitalized adults with non-viral CAP, with increased hyperglycemia but no clear increase in secondary infections.
Impact: Synthesizes high-level randomized evidence addressing previous guideline uncertainty and provides clinically meaningful mortality and ventilation benefits that can inform practice and trial design.
Clinical Implications: Consider adjunctive corticosteroids for hospitalized adults with suspected non-viral CAP to reduce short-term mortality and invasive ventilation—while instituting careful glucose monitoring and avoiding routine extrapolation to viral pneumonias.
Key Findings
- Corticosteroids probably reduce short-term (28–30 day) mortality (RR 0.82; moderate certainty).
- Corticosteroids reduce need for invasive mechanical ventilation (RR 0.63; high certainty) and may shorten ICU/hospital LOS.
- Corticosteroids probably increase hyperglycemia requiring intervention (RR 1.32) without increasing secondary infections.
2. Multicenter evaluation of the eQUANT system for use with disk diffusion AST of gram-negative bacteria directly from positive blood cultures.
A multicenter diagnostic validation showed the eQUANT system can generate a standardized inoculum (eMcFarland) directly from positive blood culture bottles, enabling same-day disk diffusion AST and saving up to 24 hours. Across 2,679 AST pairs for gram-negative rods against 12 antibiotics, categorical agreement was 95.0% with very major errors of 0.15%.
Impact: Platform-level advance that materially shortens AST turnaround without compromising accuracy, with major implications for time-to-effective therapy and antimicrobial stewardship in sepsis care.
Clinical Implications: Clinical microbiology labs can adopt eQUANT to report disk diffusion results up to 24 hours earlier, enabling faster escalation/de-escalation and potentially improving patient outcomes in bacteremic sepsis.
Key Findings
- Overall categorical agreement 95.0% across 2,679 AST result pairs compared with standard plate-subculture workflow.
- Very major error rate 0.15%, major error 0.60%, minor error 4.48%.
- Eliminates overnight subculture step and validated across 13 gram-negative species and 12 antibiotics.
3. FXR protects against neonatal sepsis by enhancing the immunosuppressive function of MDSCs.
Preclinical mechanistic study demonstrates that FXR positively regulates neonatal MDSC function; pharmacologic activation with obeticholic acid (FDA-approved FXR agonist) protects against neonatal sepsis in mice, while FXR deficiency worsens outcomes. Adoptive transfer experiments support causality between MDSC function and protection.
Impact: Links bile-acid–FXR signaling to neonatal immune regulation and proposes an immediately translatable candidate (obeticholic acid) for trials, advancing neonatal sepsis therapeutics.
Clinical Implications: Supports prioritized translational work: evaluate FXR/MDSC biomarkers in human neonates, perform dose-finding and safety studies of obeticholic acid in neonatal sepsis before efficacy trials.
Key Findings
- FXR acts as a positive regulator of neonatal MDSC function.
- Obeticholic acid protects against neonatal sepsis in an FXR-dependent manner; FXR deficiency impairs MDSC immunosuppressive and antibacterial functions.
- Adoptive transfer of MDSCs ameliorates sepsis severity, supporting causal linkage.