Daily Sepsis Research Analysis
A large multicenter randomized trial found no mortality benefit of adjunct oral zinc for young infants hospitalized with suspected sepsis, countering prior meta-analytic signals. Translational diagnostics and immunology studies highlight faster, accurate rapid AST for Gram-negative bacteremia and the amphiregulin–EGFR axis as a promising prognostic biomarker and therapeutic target in adult sepsis.
Summary
A large multicenter randomized trial found no mortality benefit of adjunct oral zinc for young infants hospitalized with suspected sepsis, countering prior meta-analytic signals. Translational diagnostics and immunology studies highlight faster, accurate rapid AST for Gram-negative bacteremia and the amphiregulin–EGFR axis as a promising prognostic biomarker and therapeutic target in adult sepsis.
Research Themes
- Adjunctive therapies in neonatal sepsis
- Rapid diagnostics and antimicrobial stewardship in bloodstream infection
- Host immuno-biomarkers and therapeutic targets (AREG–EGFR axis)
Selected Articles
1. Zinc as adjunct treatment for clinical severe infection in young infants: A randomized double-blind placebo-controlled trial in India and Nepal.
In 3,153 young infants with suspected sepsis (CSI), adjunct oral zinc for 14 days did not reduce in-hospital or 12-week mortality versus placebo, with relative risks of 0.83 (p=0.267) and 1.05 (p=0.674), respectively. Adverse events were similar except for slightly more vomiting with zinc. The trial was underpowered due to lower-than-expected event rates.
Impact: This large, multicenter, double-blind RCT provides high-level evidence that counters prior meta-analytic signals of benefit, directly informing guidelines on adjunct zinc therapy in neonatal sepsis.
Clinical Implications: Routine adjunctive zinc should not be recommended for young infants hospitalized with suspected sepsis (CSI) based on current evidence. Future trials should refine sepsis definitions or use biomarker-enriched enrollment to identify subgroups that may benefit.
Key Findings
- Among 3,153 infants (median age 25 days), in-hospital mortality was 4.1% with zinc vs 4.9% with placebo (RR 0.83; 95% CI 0.60–1.15; p=0.267).
- Twelve-week mortality was 9.0% with zinc vs 8.6% with placebo (RR 1.05; 95% CI 0.84–1.32; p=0.674).
- Adverse events were similar across arms, with a slight increase in vomiting in the zinc group; no events were attributed to the intervention.
- Lower-than-anticipated event rates and shortfall in sample size rendered the trial underpowered.
Methodological Strengths
- Randomized, double-blind, placebo-controlled design across seven hospitals with trial registration
- Large sample size and standardized dosing with predefined primary outcomes
Limitations
- Underpowered due to lower-than-expected event rates and shortfall in achieved sample size
- Broad CSI-based inclusion may have diluted treatment effect compared with more specific sepsis definitions
Future Directions: Conduct adequately powered RCTs using more specific or biomarker-based sepsis definitions, and explore subgroup effects (e.g., nutritional status, prematurity) to identify potential responders.
2. Improving time-to-result: head-to-head comparison of three rapid AST systems for Gram-negative bacteremia, including the newly developed VITEK REVEAL.
In a prospective head-to-head comparison of 220 Gram-negative positive blood cultures across 18 species, VITEK REVEAL delivered the best balance of turnaround time and accuracy, including for resistant organisms and BL/BLI combinations. Findings support laboratory adoption of rapid AST to accelerate appropriate therapy and stewardship.
Impact: This is the first prospective head-to-head evaluation including the newly developed VITEK REVEAL, directly informing diagnostic workflows to shorten time-to-result in Gram-negative bacteremia.
Clinical Implications: Adopting rapid AST (e.g., VITEK REVEAL) can accelerate susceptibility reporting directly from positive blood cultures, enabling earlier optimization of therapy and potentially improving outcomes and stewardship metrics.
Key Findings
- Prospective head-to-head comparison of VITEK REVEAL, VITEK 2-RAST, and EUCAST DD-RAST on 220 GN-positive blood cultures covering 18 species.
- VITEK REVEAL combined rapid turnaround with high accuracy, including for resistant organisms and BL/BLI antibiotics.
- Rapid AST systems can provide timely, reliable susceptibility results directly from positive blood cultures, supporting stewardship.
- Implementation success and impact on time-to-result depend on integration into laboratory workflow.
Methodological Strengths
- Prospective, head-to-head evaluation within the same cohort of positive blood cultures
- Broad organism spectrum including resistant phenotypes and BL/BLI combinations
Limitations
- Abstract does not report detailed accuracy metrics (e.g., categorical agreement, error rates) for each platform
- Findings are contextualized to EUCAST-based workflows; generalizability may vary with other standards
Future Directions: Quantify clinical impact on time-to-effective therapy, mortality, and stewardship metrics in pragmatic trials, and assess cost-effectiveness and workflow integration across diverse laboratory settings.
3. The amphiregulin- epidermal growth factor receptor axis as a therapeutic target in sepsis.
In a prospective ICU cohort (n=42) with adult sepsis, serum amphiregulin was strongly associated with in-hospital mortality (AUROC 0.87). Spectral flow cytometry characterized EGFR-expressing myeloid and lymphoid cell frequencies versus healthy volunteers, positioning the AREG–EGFR axis as a prognostic biomarker and potential therapeutic target.
Impact: This study provides first-in-adult evidence linking serum amphiregulin to mortality in sepsis with strong discriminative performance, bridging pediatric findings and highlighting a druggable pathway.
Clinical Implications: AREG could complement existing biomarkers for early risk stratification in sepsis and guide enrichment in interventional trials targeting the EGFR pathway.
Key Findings
- Serum amphiregulin demonstrated strong association with in-hospital mortality in adult sepsis (AUROC 0.87).
- Prospective analysis included 42 septic ICU patients and 20 healthy volunteers with spectral flow cytometry of EGFR-expressing immune cells.
- Findings extend prior infant data and nominate the AREG–EGFR axis as a prognostic biomarker and therapeutic target in adult sepsis.
Methodological Strengths
- Prospective design with inclusion of healthy volunteer controls
- Deep immunophenotyping using spectral flow cytometry alongside serum biomarker quantification
Limitations
- Small single-center cohort limits generalizability and precision of estimates
- Observational design precludes causal inference; external validation is needed
Future Directions: Validate AREG prognostic utility in larger, multicenter cohorts; test EGFR-pathway modulation in preclinical sepsis models; evaluate biomarker-guided trial enrichment strategies.