Weekly Sepsis Research Analysis
This week’s sepsis literature emphasizes pragmatic, practice-changing evidence and diagnostic advances. A policy-focused systematic review found no moderate/high-quality evidence that SEP‑1 compliance reduces mortality, prompting re-evaluation of sepsis quality metrics. Randomized trial data show that starting aspirin in early sepsis increases bleeding without improving organ dysfunction, and real-world plasma cell-free DNA metagenomics improved pathogen detection and changed management in a mea
Summary
This week’s sepsis literature emphasizes pragmatic, practice-changing evidence and diagnostic advances. A policy-focused systematic review found no moderate/high-quality evidence that SEP‑1 compliance reduces mortality, prompting re-evaluation of sepsis quality metrics. Randomized trial data show that starting aspirin in early sepsis increases bleeding without improving organ dysfunction, and real-world plasma cell-free DNA metagenomics improved pathogen detection and changed management in a meaningful fraction of cases. Across preclinical and translational work, new therapeutic targets (e.g., GDF15, NETs/cfDNA, APE1/NRF2) and precision diagnostics (metagenomics, multiplex SERS) are emerging.
Selected Articles
1. The Effect of Severe Sepsis and Septic Shock Management Bundle (SEP-1) Compliance and Implementation on Mortality Among Patients With Sepsis : A Systematic Review.
A comprehensive, PROSPERO-registered systematic review of 17 observational studies found inconsistent associations between SEP‑1 compliance/implementation and mortality and identified no moderate- or high-certainty evidence that SEP‑1 reduces sepsis mortality. Methodologic heterogeneity and residual confounding limited causal inference, leading the authors to recommend policy reconsideration of SEP‑1 inclusion in value-based purchasing.
Impact: Directly challenges a national quality metric (SEP‑1) by synthesizing available evidence and highlights the absence of high-quality causal data linking bundle compliance to improved mortality, with implications for policy, hospital incentives, and quality programs.
Clinical Implications: Hospitals and clinicians should prioritize interventions with proven patient-centered benefit over strict SEP‑1 process compliance; policymakers should consider redesigning sepsis quality measures toward outcome-oriented and risk-adjusted metrics.
Key Findings
- Seventeen observational studies reviewed; 12 addressed SEP‑1 compliance with mixed results (5 positive, 7 null) and 5 assessed implementation (only 1 positive but methodologically limited).
- No included study had low risk of bias; heterogeneity precluded meta-analysis and high-certainty evidence was absent.
- Authors conclude insufficient moderate/high-certainty evidence that SEP‑1 compliance or implementation reduces sepsis mortality and advise policy reconsideration.
2. Acetylsalicylic Acid Treatment in Patients With Sepsis and Septic Shock: A Phase 2, Placebo-Controlled, Randomized Clinical Trial.
Multicenter, blinded, placebo-controlled randomized trial (stopped early) showed that 200 mg/day aspirin for 7 days did not improve SOFA change but increased major bleeding and serious adverse events in adults with early sepsis/septic shock, providing high-quality evidence against initiating aspirin for organ dysfunction reduction in sepsis.
Impact: A randomized, blinded, placebo-controlled trial directly informs bedside practice by demonstrating harm (increased major bleeding) without benefit, resolving uncertainty about an inexpensive, widely available therapy in sepsis.
Clinical Implications: Do not initiate aspirin solely to reduce organ dysfunction in sepsis; re-evaluate continuation of chronic aspirin in acute sepsis with bleeding risk in mind. Antiplatelet approaches should remain within trial contexts until safer benefits are proven.
Key Findings
- No difference in SOFA change between aspirin and placebo (adjusted mean difference 0.60; 95% CI −0.55 to 1.75; p=0.30).
- Higher major bleeding in aspirin group (8.5% vs 1.2%) and more serious adverse events led to early trial termination.
- Secondary outcomes showed no benefit; study was multicenter, blinded, and placebo-controlled.
3. Metagenomic analysis of microbial cell-free DNA from plasma of patients with suspected infections: performance and therapeutic impact in clinical routine.
In a real-world retrospective cohort (147 patients, 190 samples) using a CE‑IVDD–labelled DISQVER® pipeline, plasma cfDNA metagenomics yielded a 42.1% positivity rate vs 10.2% for simultaneous blood cultures (many collected on antibiotics) with a median 2-day turnaround and resulted in 24 management changes in 20 patients (13.6%). The study supports cfDNA metagenomics as a complementary diagnostic that can alter clinical management.
Impact: Provides real-world evidence that plasma cfDNA metagenomics substantially increases pathogen detection under antibiotic exposure and meaningfully influences management decisions, supporting adoption as a complementary diagnostic in suspected sepsis.
Clinical Implications: Consider adding plasma cfDNA mNGS to the diagnostic pathway when prior antibiotics or fastidious pathogens are suspected; integrate rapid reporting and stewardship workflows to translate detection into appropriate escalation/de‑escalation.
Key Findings
- DISQVER® detected pathogens in 42.1% (80/190) of plasma samples; simultaneous blood cultures positive in 10.2% (18/176), many taken under antibiotics.
- Median time-to-result was 2 days (IQR 2–3); broad pathogen spectrum including fastidious organisms was identified.
- Results led to 24 management changes in 20/147 patients (13.6%) including escalation, de‑escalation, and device management.