Weekly Sepsis Research Analysis
This week’s sepsis literature highlights three high-impact advances: a multicenter RCT showing 7-day antibiotics are non-inferior to 14 days for uncomplicated culture-proven neonatal sepsis, physiologic-condition testing that re-establishes colistin activity against mcr-1+ Gram-negatives via host complement synergy, and validated hospital-acquired pneumonia subphenotypes that predict mortality and modify antibiotic response. Together these studies push practice-relevant changes in antibiotic ste
Summary
This week’s sepsis literature highlights three high-impact advances: a multicenter RCT showing 7-day antibiotics are non-inferior to 14 days for uncomplicated culture-proven neonatal sepsis, physiologic-condition testing that re-establishes colistin activity against mcr-1+ Gram-negatives via host complement synergy, and validated hospital-acquired pneumonia subphenotypes that predict mortality and modify antibiotic response. Together these studies push practice-relevant changes in antibiotic stewardship, prompt reconsideration of antimicrobial susceptibility testing paradigms, and enable prognostic/predictive enrichment for respiratory infection trials. Several translational and diagnostic signals (EV miRNAs, BALF epigenetic markers, ML-enabled rapid ESR kinetics) further expand therapeutic and triage toolkits.
Selected Articles
1. Seven-day versus 14-day antibiotic course for culture-proven neonatal sepsis: a multicentre randomised non-inferiority trial in a low and middle-income country.
In a multicenter, randomized non-inferiority trial of neonates (BW ≥1000 g) with culture-proven sepsis who clinically remitted by day 7, a 7-day antibiotic course was non-inferior to 14 days for relapse within 21 days and shortened median hospital stay by 4 days. The trial enrolled 261 infants and used masked outcome assessment.
Impact: Provides high-quality randomized evidence directly supporting shorter antibiotic regimens in a well-defined neonatal subgroup — a practice-changing result for stewardship, costs, and resistance mitigation.
Clinical Implications: Clinicians may consider a 7-day antibiotic course for clinically improving, culture-proven neonatal sepsis (BW ≥1000 g, remission by day 7), with appropriate follow-up. Implementation should respect inclusion criteria and local pathogen profiles.
Key Findings
- Seven-day regimen non-inferior to 14-day regimen for relapse within 21 days post-treatment completion.
- Median hospital stay was reduced by 4 days in the 7-day group.
2. Colistin exerts potent activity against mcr+ Enterobacteriaceae via synergistic interactions with the host defense.
Under physiologically relevant media (bicarbonate-containing) and in ex vivo fresh human blood, colistin retained bactericidal activity against mcr-1+ E. coli, K. pneumoniae and S. enterica, enhanced complement deposition, synergized with human serum, and was effective as monotherapy in a murine bacteremia model — challenging conventional AST conclusions.
Impact: Challenges current microbiology paradigms by showing that standard enriched-media AST can miss clinically relevant host–drug synergies; suggests colistin may have a role against mcr-1+ bloodstream infections under physiological conditions.
Clinical Implications: Microbiology labs and clinicians should consider physiologic-condition testing or interpret AST in the context of host factors (complement competence); prospective clinical evaluation of colistin for select mcr-1+ bacteremias is warranted.
Key Findings
- Colistin killed mcr-1+ Enterobacteriaceae in bicarbonate-containing tissue culture medium whereas conventional AST did not detect activity.
- Colistin enhanced complement deposition and synergized with human serum; killed mcr-1+ strains in fresh human blood and was effective in a murine bacteremia model.
3. Identification and validation of robust hospital-acquired pneumonia subphenotypes associated with all-cause mortality: a multi-cohort derivation and validation.
Using four international derivation cohorts and independent validation in an RCT dataset (VITAL), investigators identified two reproducible HAP subphenotypes. The high-risk subphenotype had worse physiology, higher inflammation and respiratory microbiome dysbiosis, higher 28-day mortality and treatment failure, and showed antibiotic effect modification — enabling prognostic and predictive enrichment.
Impact: Provides externally validated, biologically coherent subphenotypes that predict outcomes and modify antibiotic effects — a practical advance for stratified trials and personalized management in hospital-acquired respiratory infection.
Clinical Implications: Incorporating subphenotype classifiers into clinical pathways could identify patients needing intensified monitoring or alternative therapies and enable trials that enroll patients most likely to benefit from targeted interventions.
Key Findings
- Two robust HAP subphenotypes were reproducibly identified across four cohorts; subphenotype 2 had greater severity, inflammation, microbiome dysbiosis, and higher 28-day mortality.
- Subphenotype assignment modified antibiotic treatment effect in an independent RCT (VITAL), supporting predictive enrichment potential.