Daily Sepsis Research Analysis
Analyzed 8 papers and selected 3 impactful papers.
Summary
Analyzed 8 papers and selected 3 impactful articles.
Selected Articles
1. Identifying Rate-Limiting Steps in the Antimicrobial Workflow for Community-Onset Sepsis.
In 3,623 patients with community-onset sepsis, the median time from arrival to antimicrobial administration varied by workflow sequence, with the shortest times when antimicrobials were given before culture collection. The rate-limiting step differed across groups, and concurrently ordering antibiotics and blood cultures was associated with faster administration.
Impact: Identifying workflow-specific bottlenecks provides actionable targets to reduce time-to-antibiotics, a modifiable determinant of sepsis outcomes. The large multicenter design enhances generalizability for system-level quality improvement.
Clinical Implications: Adopt concurrent ordering of blood cultures and antimicrobials and streamline prescription-to-administration processes (e.g., premixed antibiotics, nurse-initiated protocols) to shorten time-to-antibiotics in community-onset sepsis.
Key Findings
- Among 3,623 patients, median time to antimicrobial administration was 63.5 min (Group C), 87.0 min (Group A), and 115.0 min (Group B).
- The rate-limiting step differed: prescription-to-administration (Group A), time-zero-to-prescription (Group B), and culture prescription-to-collection (Group C).
- Septic shock was associated with shorter intervals overall, except for an unchanged prescription-to-administration interval.
- Concurrent ordering of antibiotics and blood cultures was associated with shorter time-to-antibiotics.
Methodological Strengths
- Prospective multicenter cohort with a large sample size (N=3,623)
- Predefined workflow timepoints enabling granular process analysis
Limitations
- Observational design with potential residual confounding and indication bias
- Single-country setting may limit generalizability; no patient-centered outcomes reported
Future Directions: Test workflow bundles (e.g., concurrent orders, antibiotic kits, expedited pharmacy processes) in pragmatic trials to validate reductions in time-to-antibiotics and assess impact on mortality and organ failure.
OBJECTIVES: To characterise time intervals preceding antimicrobial administration in community-onset sepsis and identify rate-limiting steps. METHODS: In this multicentre prospective observational study of patients with community-onset sepsis in South Korea (June 2020-December 2023), the antimicrobial workflow was defined by five time points: time zero, blood culture prescription and collection, and antimicrobial prescription and administration. Patients were categorised into three groups by step sequence, and four key intervals were analysed. RESULTS: Among 3,623 patients (mean age 74.3 ± 13.0 years; 56.6% male), 1,838 (50.7%) were assigned to Group A (antimicrobials and cultures prescribed before culture collection), 1,517 (41.9%) to Group B (cultures obtained before antimicrobial prescription), and 268 (7.4%) to Group C (antimicrobials given before culture collection). Median time from time zero to administration was shortest in Group C (63.5 min), then Group A (87.0 min) and Group B (115.0 min). The rate-limiting step differed by group: prescription-to-administration in Group A, time-zero-to-prescription in Group B, and culture prescription-to-collection in Group C. Septic shock was associated with shorter intervals overall, except prescription-to-administration, which was unchanged. CONCLUSIONS: Rate-limiting steps in antimicrobial delivery differ by clinical workflow. Early concurrent prescription of antimicrobials and blood cultures was associated with shorter time to antimicrobial administration.
2. Obesity and Early Sepsis-Associated Acute Respiratory Distress Syndrome: A Prospective Multicenter Study.
Among 1,799 adults with sepsis, obesity markedly increased the risk of SA-ARDS under both Berlin and HFNC-integrated definitions, with effects robust to PSM and IPW. The apparent obesity-related survival advantage under the Berlin definition disappeared when HFNC recipients were included in the expanded definition.
Impact: Clarifies how evolving ARDS definitions alter the observed ‘obesity paradox’ and quantifies obesity’s strong effect on SA-ARDS incidence. This informs risk stratification and cohort definition for future trials.
Clinical Implications: Screen obese sepsis patients early for respiratory deterioration and apply ARDS prevention/monitoring strategies; interpret survival analyses cautiously across differing ARDS definitions, especially when HFNC patients are included.
Key Findings
- Obesity independently increased SA-ARDS incidence under the HFNC-integrated definition (adjusted OR 5.61; 95% CI 4.56–6.92; AUC 0.700).
- Risk was also elevated under the Berlin ARDS definition (OR 6.66; 95% CI 5.01–8.91) and among HFNC recipients (OR 5.77; 95% CI 3.85–8.85).
- Associations were robust in propensity score matching (PSM) and inverse probability weighting (IPW) analyses.
- No BMI-related survival differences were observed under the expanded ARDS definition, whereas under Berlin, obesity was associated with lower 90-day mortality in select subgroups.
Methodological Strengths
- Prospective multicenter cohort with predefined primary and secondary outcomes
- Robust confounding control using PSM and IPW across alternative ARDS definitions
Limitations
- Observational design limits causal inference and residual confounding may persist
- External validity may vary due to heterogeneity in HFNC use thresholds and practices
Future Directions: Evaluate ARDS prevention and early respiratory support strategies tailored to obese sepsis patients; harmonize ARDS definitions in trials to minimize misclassification and paradoxical survival signals.
PURPOSE: The role of obesity in sepsis-associated acute respiratory distress syndrome (SA-ARDS) remains uncertain, particularly amid evolving diagnostic criteria. We aimed to assess whether obesity differentially influences SA-ARDS incidence and mortality under the Berlin definition versus an expanded framework incorporating high-flow nasal cannula (HFNC). METHODS: This prospective multicenter cohort study included 1,799 adults with sepsis 3.0 from three ICUs. SA-ARDS was diagnosed using (1) Berlin criteria and (2) a new definition integrating HFNC. The primary outcome was incidence of SA-ARDS. Secondary outcomes included 28- and 90-day mortality in SA-ARDS patients. RESULTS: Obesity was independently associated with elevated SA-ARDS incidence under the new definition (adjusted OR 5.61, 95% CI 4.56-6.92; AUC = 0.700), with even higher risk in ARDS patients under Berlin criteria (OR 6.66, 95% CI 5.01-8.91) and HFNC recipients (OR 5.77, 95% CI 3.85-8.85). These associations remained robust in PSM and IPW analyses. However, in ARDS patients of the new definition (including HFNC patients), no survival differences were observed across BMI categories. However, under the Berlin definition, obesity patients had significantly lower 90-day mortality than underweight and normal-weight patients, particularly in the elderly and those with prolonged hospital stays (P < 0.05). CONCLUSIONS: Obesity independently increased SA-ARDS risk across both diagnostic frameworks. However, the mortality benefit (Berlin definition) was absent when using the expanded criteria incorporating HFNC. This indicates obesity drives susceptibility but confers no universal survival advantage in new ARDS cohorts.
3. Longitudinal immune-inflammatory profiles and mortality in older adults with sepsis: a multicentre prospective cohort study.
In a multicenter cohort of 1,851 adults aged ≥60, sepsis was distinguished from nonsevere infection by lower cellular immune markers and higher cytokine levels. These patterns were evident by ICU day 1, persisted over days 1–7 among available measurements, and day-1 biomarkers were associated with in-hospital mortality.
Impact: Provides a comprehensive immune-inflammatory atlas across the infection spectrum in older adults and links early immune signatures to mortality, informing stratified trial design and potential immunomodulatory targets.
Clinical Implications: Early measurement of cellular immune counts and cytokines in older adults with suspected sepsis may enhance risk stratification and guide enrollment into immunomodulatory trials.
Key Findings
- In 1,851 participants (≥60 years), sepsis showed lower circulating cellular immune markers and higher cytokine levels versus nonsevere infection and controls.
- Separation of immune-inflammatory profiles was evident on ICU day 1 and remained observable through day 7 among available measurements.
- Day-1 biomarkers were associated with in-hospital mortality in sepsis per Cox regression.
- Comprehensive profiling included immune-cell subsets, cytokines, complement components, and routine laboratory indices.
Methodological Strengths
- Large multicenter prospective cohort with comprehensive immune profiling
- Longitudinal modeling (linear mixed-effects) and adjusted analyses (multivariable regression, Cox)
Limitations
- Observational design precludes causal inference
- Potential missingness in scheduled measurements and limited generalizability beyond older adults
Future Directions: Validate predictive performance of day-1 immune signatures in external cohorts and test biomarker-guided immunomodulatory strategies in randomized trials.
BACKGROUND: Older adults are at high risk of sepsis, but the immune-inflammatory features distinguishing sepsis from nonsevere infection and their prognostic relevance remain incompletely defined. We aimed to characterize immune-inflammatory profiles across the older adult infection spectrum and evaluate their longitudinal association with in-hospital mortality. METHODS: In this multicentre prospective observational cohort, 1,851 participants aged ≥ 60 years were enrolled, including healthy controls, patients with nonsevere infection, and patients with sepsis. Immune-cell subsets, cytokines, complement components, and routine laboratory indices were assessed. Adjusted cross-sectional comparisons were performed using multivariable linear regression. Among patients with sepsis, model-estimated longitudinal profiles from intensive care unit (ICU) day 1 to day 7 were analysed using linear mixed-effects models among available scheduled measurements, and day-1 biomarkers associated with in-hospital mortality were evaluated using Cox regression. RESULTS: The cohort included 524 healthy controls, 511 patients with nonsevere infection, and 816 patients with sepsis. Across the infection spectrum, sepsis was characterized by progressively lower circulating lymphocyte, T-cell, cluster of differentiation 8 (CD8 CONCLUSIONS: In older adults, sepsis was associated with an adjusted circulating immune-inflammatory pattern characterized by lower cellular immune markers and higher cytokine levels. This separation was evident on ICU day 1 and remained observable among patients with available follow-up measurements. Given the observational design, these associations should not be interpreted as causal.