Daily Sepsis Research Analysis
Three impactful studies span surveillance, diagnostics, and stewardship in sepsis-related care. A Lancet Public Health regional analysis quantifies the Eastern Mediterranean’s bacterial AMR burden and forecasts substantial rises by 2050. An ambispective cohort links histone H3K18 lactylation/acetylation signatures to sepsis diagnosis and severity, while a cohort study shows direct disk diffusion testing accelerates susceptibility reporting and improves antibiotic appropriateness in Gram‑negative
Summary
Three impactful studies span surveillance, diagnostics, and stewardship in sepsis-related care. A Lancet Public Health regional analysis quantifies the Eastern Mediterranean’s bacterial AMR burden and forecasts substantial rises by 2050. An ambispective cohort links histone H3K18 lactylation/acetylation signatures to sepsis diagnosis and severity, while a cohort study shows direct disk diffusion testing accelerates susceptibility reporting and improves antibiotic appropriateness in Gram‑negative bacteremia.
Research Themes
- Regional AMR burden modeling and forecasts relevant to sepsis
- Epigenetic biomarkers (histone lactylation/acetylation) for sepsis diagnosis and severity
- Rapid susceptibility testing to improve antimicrobial stewardship in bacteremia/sepsis
Selected Articles
1. The burden of bacterial antimicrobial resistance in the WHO Eastern Mediterranean Region 1990-2021: a cross-country systematic analysis with forecasts to 2050.
This cross-country modeling study estimated 380,000 AMR-associated and 92,800 AMR-attributable deaths in the EMR in 2021, with declines among children under five but marked increases in adults ≥70. Six pathogens dominated burden (S. pneumoniae, K. pneumoniae, E. coli, S. aureus, A. baumannii, P. aeruginosa), with MRSA prominent. Forecasts project substantial rises by 2050, highlighting wide between-country heterogeneity and urgent needs for targeted mitigation.
Impact: Provides the most comprehensive EMR AMR burden estimates and forecasts, directly informing policy, surveillance, and stewardship strategies relevant to sepsis care.
Clinical Implications: Prioritize MRSA and Gram-negative threats in stewardship and vaccination agendas; strengthen lab capacity and surveillance; tailor interventions for older adults and high-burden countries; allocate resources based on forecasted trajectories.
Key Findings
- Estimated 380,000 AMR-associated and 92,800 AMR-attributable deaths in EMR in 2021.
- Under-5 AMR-associated deaths decreased by 50.0% since 1990, while ≥70 years increased by >85.7%.
- Six pathogens dominated burden; MRSA was a leading pathogen–drug combination.
- Somalia had the highest age-standardized AMR mortality; Qatar the lowest.
- By 2050, deaths attributable to AMR projected at 187,000 and associated deaths at 752,000.
Methodological Strengths
- Multi-source, multistage modeling with counterfactual scenarios and 95% uncertainty intervals.
- Out-of-sample cross-validation and country-level estimates spanning 1990–2021 with forecasts.
Limitations
- Modeled estimates depend on data completeness and quality, which vary widely across countries.
- Residual confounding and misclassification possible; not an interventional study.
Future Directions: Enhance national surveillance and data sharing, evaluate impact of targeted interventions (e.g., MRSA and Gram-negative control), and integrate vaccination and stewardship modeling.
2. The Roles of Histone H3K18 Lactylation, Acetylation, and Lactylation/Acetylation Ratio as Potential Biomarkers in the Diagnosis and Severity Assessment of Sepsis and Septic Shock.
In an ambispective cohort (86 critically ill patients plus 12 healthy volunteers), H3K18 lactylation increased and H3K18 acetylation decreased in infection, with the H3K18la/ac ratio independently discriminating infection and correlating with sepsis severity. H3K18la and the ratio positively associated with SOFA scores, ICU length of stay, and ventilation time; cytokine and macrophage polarization gene correlations support mechanistic relevance.
Impact: Introduces epigenetic histone modification signatures as dual diagnostic and severity biomarkers with mechanistic links to macrophage polarization in sepsis.
Clinical Implications: Potential for a PBMC-based H3K18la/ac panel to complement CRP/PCT for early diagnosis and risk stratification, guiding monitoring intensity and immunomodulatory strategies.
Key Findings
- Infection increased H3K18la and H3K18la/ac and decreased H3K18ac versus noninfectious controls; H3K18la/ac independently discriminated infection.
- Septic shock showed higher H3K18la and H3K18la/ac and lower H3K18ac than sepsis without shock.
- H3K18la and H3K18la/ac positively correlated with SOFA scores, ICU length of stay, and ventilation time; H3K18ac correlated negatively.
- Cytokine correlations (e.g., H3K18la negative with IFN-α and IL-5; positive with IL-10) and associations with ARG1 and KLF4 mRNA suggest links to macrophage polarization.
Methodological Strengths
- Ambispective cohort with defined infection and noninfectious comparators plus healthy controls.
- Multimodal assays (Western blot PBMC histone marks, cytokines, qPCR for ARG1/KLF4) with regression, ROC, and correlation analyses.
Limitations
- Single-center, relatively small sample size limits generalizability and precision.
- Observational design; lacks external validation and prospective clinical utility testing.
Future Directions: Prospective multicenter validation, assay standardization, thresholds for triage, and interventional studies targeting lactylation pathways.
3. Clinical utility of direct disk diffusion testing in guiding antibiotic therapy for gram-negative bacteremia.
Implementing dDDT for Gram-negative bacteremia reduced time to susceptibility results by 24 hours, improved appropriateness of therapy for MDROs (76.5% to 91.2%), and optimized escalation/de-escalation per Antibiotic Spectrum Index. Although Kaplan–Meier curves showed lower cumulative mortality post-dDDT, it was not an independent predictor in adjusted models.
Impact: Demonstrates a pragmatic, scalable laboratory intervention that accelerates AST reporting and meaningfully improves antibiotic stewardship, directly relevant to sepsis care pathways.
Clinical Implications: Adopting dDDT can shorten time-to-targeted therapy, increase appropriateness for MDROs, and support timely de-escalation, with stewardship teams interpreting early results while confirming with standard AST.
Key Findings
- dDDT reduced time to susceptibility results by 24 hours (37.6 ± 14.3 vs. 61.6 ± 16.3 hours).
- Appropriate therapy for MDROs improved from 76.5% to 91.2% (P = 0.048).
- Antibiotic Spectrum Index analysis showed appropriate escalation for MDROs and de-escalation for non-MDROs.
- Lower cumulative 30-day mortality post-dDDT by Kaplan–Meier (P = 0.023), but not an independent predictor in multivariable Cox (aHR 1.27, 95% CI 0.76–2.14).
Methodological Strengths
- Before–after cohort with multivariate Cox modeling and sensitivity analyses.
- Composite stewardship metrics (appropriateness, Antibiotic Spectrum Index) alongside clinical outcomes.
Limitations
- Retrospective design with potential confounding and secular trends.
- Generalizability may be limited; mortality benefit not independent after adjustment.
Future Directions: Prospective multicenter trials to confirm clinical impact, cost-effectiveness analyses, and integration with rapid diagnostics and stewardship algorithms.