Daily Sepsis Research Analysis
Analyzed 48 papers and selected 3 impactful papers.
Summary
Analyzed 48 papers and selected 3 impactful articles.
Selected Articles
1. Individualised duration of antibiotic treatment in culture-negative early-onset sepsis in late-preterm and term-born neonates in Denmark (DURATION): a multicentre, open-label, randomised, controlled, non-inferiority trial.
In a nationwide multicentre non-inferiority RCT of 493 neonates with culture-negative early-onset sepsis, a clinically guided individualized strategy safely reduced antibiotic duration to a median of 3 days and was non-inferior to standard 5–7 day therapy regarding infection-related readmissions. Trial registration NCT05329701.
Impact: This trial directly supports antibiotic stewardship in neonates by demonstrating that individualized cessation safely reduces exposure without compromising outcomes.
Clinical Implications: For late-preterm and term neonates with probable culture-negative EOS, consider CRP- and clinical trajectory-guided early discontinuation after 24 hours of stability to reduce antibiotic exposure.
Key Findings
- Individualized strategy met non-inferiority for infection-related readmission (risk difference 0.4%, 95% CI −1.5 to 2.6).
- Median antibiotic duration was reduced to 3 days in the individualized group versus 5–7 days standard care.
- Randomized 493 neonates across multiple centers; initiation of therapy occurred at ~22.5–24.5 hours after birth.
Methodological Strengths
- Nationwide multicentre randomized, controlled non-inferiority design with prespecified co-primary outcomes.
- Operationalized, clinically actionable stopping rule using CRP trajectory plus clinical signs.
Limitations
- Open-label design may introduce performance bias.
- Findings apply to culture-negative EOS in late-preterm/term infants; not generalizable to culture-positive cases or very preterm infants.
Future Directions: Evaluate implementation in diverse health systems, refine biomarker thresholds, and test applicability in very preterm infants and culture-positive EOS.
BACKGROUND: Suspicion of early-onset sepsis (EOS) is a major contributor to antibiotic use in late-preterm and term-born neonates. We aimed to evaluate whether a clinically guided, individualised approach to treatment duration could safely reduce antibiotic exposure compared with standard care. METHODS: This nationwide, multicentre, open-label, randomised, controlled, non-inferiority trial included late-preterm and term-born neonates (aged 0-3 days, gestational age 35 weeks or more, birthweight 2000 g or more) with culture-negative early-onset sepsis (probable EOS), defined as continuation of antibiotic treatment beyond 36-48 h based on clinical signs of or maternal risk factors for infection in combination with elevated C-reactive protein and symptom onset less than 72 h after birth. Neonates were ineligible if they met the criteria for discontinuing antibiotics before 48 h. Participants were randomised (1:1) to individualised or standard treatment. In the individualised group, antibiotic treatment was discontinued after 24 h without clinical signs of infection, provided that C-reactive protein was declining to ≤30 mg/L. Standard treatment was 5-7 days. The coprimary outcomes were readmission due to bacterial infection (non-inferiority margin 4%) and total antibiotic duration (superiority assessment), performed on both intention-to-treat and per-protocol populations. Safety was assessed in all included neonates. This study was registered with ClinicalTrials.gov (NCT05329701) and is completed. FINDINGS: Between April 22, 2022, and April 5, 2025, 493 (61%) of 811 eligible neonates were randomly assigned to individualised (n=246) or standard (n=247) duration. Antibiotic therapy was initiated at a median of 22·5 h (IQR 14·4-28·0) after birth in the individualised group and 24·5 h (16·6-28·0) in the standard group. Readmission due to bacterial infection occurred in two (1%) of 246 neonates in the individualised group and one (<1%) of 247 in the standard group (risk difference 0·4% [95% CI -1·5 to 2·6]; p INTERPRETATION: In neonates with probable EOS, a clinically guided, individualised treatment strategy was non-inferior to standard therapy with respect to infection-related readmission and reduced treatment duration to a median of 3 days. These findings support reduced antibiotic use through individualised treatment duration strategies. FUNDING: Copenhagen University Hospital Rigshospitalet Research Fund, Innovation Fund Denmark, and Greater Copenhagen Health Science Partners.
2. Performance of Sepsis-3 criteria in burn patients: A multicenter real-world study.
Across 527,197 adult burn admissions, Sepsis-3, ABA, and Mann-Salinas criteria had high sensitivity but low PPV in a low-prevalence setting, functioning mainly as screening tools. Mann-Salinas showed the best balance of sensitivity and specificity; 28-day mortality did not differ by definition.
Impact: Provides large-scale, real-world validation of sepsis definitions in burn care, guiding clinicians toward balanced screening and confirmatory testing strategies.
Clinical Implications: Use sepsis criteria in burn patients as sensitive screens; consider Mann-Salinas when prioritizing specificity and pair with microbiological confirmation and clinical judgment to reduce overclassification.
Key Findings
- Among 527,197 adult burn patients, 1.4% had clinically documented sepsis within 7 days.
- Sensitivity: ABA 86.7%, Mann-Salinas 86.6%, Sepsis-3 81.4%; Specificity: Mann-Salinas 77.0%, ABA 61.6%, Sepsis-3 45.8%.
- PPVs were 2.5%–6.0% with NPVs >99% for all definitions; 28-day mortality did not differ across definitions.
Methodological Strengths
- Very large, multicenter real-world dataset with standardized outcome windows (7-day sepsis identification; 28-day mortality).
- Use of propensity score methods and Cox models to assess prognostic relevance.
Limitations
- Retrospective design and reliance on ICD-10 coding for reference standard may misclassify cases.
- Low prevalence limits PPV and may overestimate screening positives; lacks microbiological adjudication.
Future Directions: Prospective validation combining physiologic criteria with pathogen confirmation and host-response biomarkers to improve positive predictive value in burn populations.
Sepsis remains a leading cause of morbidity and mortality among patients with burn injury, yet diagnosis is particularly challenging because burn-induced hypermetabolic and inflammatory responses frequently mimic infection-related organ dysfunction. Although multiple sepsis definitions are used in clinical practice, their diagnostic performance and prognostic relevance in real-world burn populations remain uncertain. We conducted a retrospective multicenter validation study using the TriNetX U.S. Collaborative Network. Adult patients hospitalized with burn injury were identified. Clinically documented sepsis, defined by ICD-10-CM codes A40, A41, or R65.2 occurring within 7 days after the index burn event, served as the reference standard. The diagnostic accuracy of Sepsis-3, American Burn Association (ABA), and Mann-Salinas (MN) criteria was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Prognostic relevance was evaluated by comparing 28-day all-cause mortality across sepsis definitions using propensity score-matched cohorts and Cox proportional hazards models. Among 527,197 adult burn patients, 8810 (1.4%) had clinically documented sepsis. Sensitivity was high across definitions (ABA, 86.7%; Mann-Salinas, 86.6%; Sepsis-3, 81.4%), whereas specificity varied substantially (Mann-Salinas, 77.0%; ABA, 61.6%; Sepsis-3, 45.8%). PPVs were uniformly low (2.5%-6.0%), reflecting substantial overclassification in this low-prevalence population, while NPVs exceeded 99% for all criteria. No significant differences in 28-day mortality were observed between definitions, with all pairwise hazard ratios overlapping and crossing unity. In adult burn patients, commonly used sepsis definitions function primarily as sensitive screening tools rather than confirmatory diagnostic instruments. The Mann-Salinas criteria demonstrated the most balanced performance. Sepsis assessment in burn populations should integrate physiologic criteria, clinical judgment, and confirmatory infection testing.
3. Management of Gram-Negative Bloodstream Infections With Oral Antibiotics in Solid Organ Transplant Recipients.
In 60 solid organ transplant recipients with monomicrobial gram-negative bacteremia, early step-down to oral therapy (often fluoroquinolones) achieved 90% clinical success with a median total duration of 14 days (4 days IV, 10 days oral). This supports feasibility of oral step-down in immunosuppressed hosts when pathogens are susceptible.
Impact: Addresses a key evidence gap by extending oral step-down strategies to transplant recipients—a high-risk, historically excluded population.
Clinical Implications: In clinically stable SOT recipients with source control and a susceptible gram-negative isolate, consider early oral step-down (e.g., fluoroquinolones) with close monitoring, pending larger prospective validation.
Key Findings
- Clinical success (no 30-day mortality, no recurrence, no symptom worsening without therapy change) was achieved in 90% of 60 SOT recipients.
- Median total antibiotic duration was 14 days, comprising a median of 4 days IV followed by 10 days oral therapy.
- Escherichia coli was the most common pathogen (58.3%); fluoroquinolones were the predominant oral agents (90%).
Methodological Strengths
- Clearly defined composite clinical success endpoint capturing mortality, recurrence, and symptom trajectory.
- Focus on a clinically important, under-studied high-risk group (solid organ transplant recipients).
Limitations
- Single-center retrospective design with small sample size and no concurrent IV-only comparator arm.
- Predominant use of fluoroquinolones may limit generalizability where resistance is high or contraindications exist.
Future Directions: Prospective, multicenter trials comparing standardized IV-to-oral step-down versus full IV therapy in SOT recipients, with resistance- and source-specific subgroup analyses.
BACKGROUND: Transitioning from intravenous (IV) to oral antibiotics upon clinical stability in gram-negative rod (GNR) bloodstream infections (BSI) in immunocompetent patients is effective, with comparable clinical success rates as IV therapy. Studies have historically excluded solid organ transplant (SOT) recipients. This study aims to describe the clinical outcomes of SOT patients who transitioned to oral therapy to manage GNR BSIs. METHODS: This retrospective observational cohort was conducted at the Medical University of South Carolina Health between January 2018 and August 2023. SOT recipients 18 years or older with a positive monomicrobial GNR blood culture and a susceptible oral agent were included. The primary outcome was composite clinical success, encompassing the absence of 30-day mortality, microbiology recurrence, or worsening symptoms without therapy modification. RESULTS: Two hundred and one patients were screened, with 60 meeting the criteria for analysis. The median age was 58 (IQR 50-67) years, 56.7% were male, and 70% had a kidney transplant. The most common causative pathogen was Escherichia coli (58.3%), and the most frequently used oral agents were fluoroquinolones (90.0%). The primary outcome of clinical success was achieved in 90% of patients. The median duration of total therapy was 14 (IQR 13-14) days, which included 4 (IQR 3-5) days of IV therapy and 10 (IQR 8-11) days of oral therapy. CONCLUSION: This study outlines our institutional experience with transitioning to oral therapy to manage gram-negative BSI in SOT recipients, demonstrating high clinical success rates. Larger prospective studies in this population are necessary to substantiate and validate our findings.