Daily Sepsis Research Analysis
Analyzed 33 papers and selected 3 impactful papers.
Summary
Analyzed 33 papers and selected 3 impactful articles.
Selected Articles
1. Antibiotic De-Escalation in Adults Hospitalized for Community-Onset Sepsis.
In a 67-hospital target trial emulation of 36,924 adults with community-onset sepsis, day-4 de-escalation of anti-MRSA or anti-Pseudomonas coverage was associated with similar 90-day mortality to continued broad-spectrum therapy. De-escalation reduced antibiotic days and shortened hospitalization, with substantial inter-hospital practice variation.
Impact: Provides high-quality causal evidence supporting safe antibiotic de-escalation in sepsis, directly informing stewardship and reducing exposure without compromising survival.
Clinical Implications: In adults with community-onset sepsis lacking evidence of multidrug-resistant infection, day-4 de-escalation of empiric anti-MRSA/anti-Pseudomonas therapy can be adopted to reduce antibiotic exposure and length of stay without increasing mortality.
Key Findings
- De-escalation of anti-MRSA and anti-Pseudomonas coverage at day 4 had similar 90-day mortality to continued broad-spectrum therapy (OR 1.00 and 0.98, respectively).
- De-escalation reduced antibiotic days through day 14 (RR 0.91 for both comparisons) and shortened hospitalization (RR 0.88–0.91).
- There was more than a twofold variation in de-escalation rates across 67 hospitals.
Methodological Strengths
- Target trial emulation with inverse probability of treatment weighting to balance confounders
- Large, multicenter cohort across 67 hospitals with prespecified day-4 decision point
Limitations
- Observational design; residual confounding and indication bias cannot be fully excluded
- Generalizability may be limited to similar hospital networks and stewardship practices
Future Directions: Cluster-randomized trials or stepped-wedge evaluations to test standardized de-escalation protocols; integration with rapid diagnostics to refine day-4 decision-making.
2. Quantifying the bystander effect of antimicrobial use on the gut microbiome and resistome in Malawian adults.
Longitudinal metagenomics in Malawian adults revealed pronounced bystander effects of antibiotics on the gut ecology. Ceftriaxone specifically increased Enterobacterales abundance and enriched macrolide and aminoglycoside resistance genes, with Bayesian models enabling simulation of stewardship strategies.
Impact: First robust quantification of antibiotic bystander effects on the gut microbiome/resistome in a low-income setting, linking specific agents to ecological shifts that drive resistance.
Clinical Implications: Supports stewardship policies that limit ceftriaxone where suitable alternatives exist and encourages integrating microbiome-resistome monitoring to mitigate downstream resistance risk.
Key Findings
- Longitudinal stool metagenomics pre-, during-, and post-antimicrobial exposure captured dynamic microbiome and resistome changes.
- Ceftriaxone was linked to increased Enterobacterales abundance and higher prevalence of macrolide and aminoglycoside resistance genes.
- Bayesian regression enabled attribution of off-target effects to specific agents and simulations of stewardship scenarios.
Methodological Strengths
- Deep metagenomic sequencing with longitudinal sampling across exposure windows
- Bayesian modeling to attribute drug-specific ecological effects and enable policy simulations
Limitations
- Sample size and participant diversity are not detailed; single-city context may limit generalizability
- Observational design cannot fully exclude confounding by co-medications, diet, or comorbidities
Future Directions: Scale-up to multicenter cohorts with clinical outcome linkage; interventional trials testing stewardship policies informed by microbiome-resistome modeling.
3. C-reactive protein in adult sepsis: systematic review and meta-analysis.
Across 22 studies (13,083 adults), CRP showed pooled sensitivity of 83% but low specificity of 56% for sepsis diagnosis with high heterogeneity, and limited prognostic accuracy. The review underscores substantial diagnostic uncertainty, challenging CRP’s role as a standalone decision tool.
Impact: Provides comprehensive evidence that a widely used biomarker lacks sufficient specificity and prognostic performance in adult sepsis, redirecting diagnostic strategies toward multimodal approaches.
Clinical Implications: CRP should not be used alone for diagnosing or risk stratifying adult sepsis; integration with clinical assessment and other biomarkers or scores is recommended.
Key Findings
- Meta-analysis of 22 studies (13,083 patients) found pooled diagnostic sensitivity 83% and specificity 56% for CRP in adult sepsis.
- Prognostic accuracy was limited, and heterogeneity across studies was high.
- Risk of bias was assessed using QUADAS-2 and evidence quality graded with GRADE.
Methodological Strengths
- Comprehensive search across multiple databases without language/time restrictions
- Use of standardized tools (QUADAS-2, GRADE) to assess bias and evidence quality
Limitations
- High heterogeneity and variable CRP thresholds across included studies
- Mixture of cross-sectional and cohort designs; timing of CRP sampling varied
Future Directions: Prioritize multimarker panels and dynamic trajectories (e.g., serial measurements) and evaluate combined clinical-biomarker algorithms in prospective studies.