Daily Sepsis Research Analysis
A multicentre RCT shows that a 7-day antibiotic course is non-inferior to 14 days for uncomplicated culture-proven neonatal sepsis, shortening hospital stay. Two preclinical advances highlight novel sepsis therapies: a rejuvenation-associated extracellular vesicle microRNA (miR-296-5p) that reduces inflammation and mortality in mice, and an engineered extracorporeal device that removes intact bacteria from blood via red blood cell-induced margination.
Summary
A multicentre RCT shows that a 7-day antibiotic course is non-inferior to 14 days for uncomplicated culture-proven neonatal sepsis, shortening hospital stay. Two preclinical advances highlight novel sepsis therapies: a rejuvenation-associated extracellular vesicle microRNA (miR-296-5p) that reduces inflammation and mortality in mice, and an engineered extracorporeal device that removes intact bacteria from blood via red blood cell-induced margination.
Research Themes
- Antibiotic stewardship and duration optimization in neonatal sepsis
- Extracellular vesicle and microRNA-based immunomodulation
- Extracorporeal blood purification engineering for bacteremia
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 multicentre non-inferiority RCT, a 7-day antibiotic regimen was non-inferior to 14 days for uncomplicated culture-proven neonatal sepsis. Relapse within 21 days post-therapy was similar or lower with 7 days, and hospital stay was shorter by a median of 4 days.
Impact: Provides high-quality evidence to safely shorten antibiotic duration in neonatal sepsis, with implications for antimicrobial stewardship, costs, and resistance.
Clinical Implications: For clinically improving neonates with culture-proven sepsis, a 7-day course may be adequate, reducing hospital days and antibiotic exposure. Implementation should consider inclusion criteria (BW ≥1000 g, remission by day 7) and local pathogens.
Key Findings
- Seven-day antibiotics were non-inferior to 14-day therapy for uncomplicated neonatal sepsis.
- Primary outcome (relapse within 21 days post-completion): 2/125 vs 6/130 (risk difference −3.0%, 99.5% CI −9.2% to +3.1%).
- Composite secondary outcome favored 7 days, and median hospital stay was 4 days shorter.
Methodological Strengths
- Multicentre randomised controlled non-inferiority design with masked outcome assessment
- Registered trial (NCT03280147) with predefined primary endpoint
Limitations
- Early trial termination after interim per-protocol analysis
- Generalizability limited to neonates ≥1000 g with clinical remission by day 7; clinician blinding not described
Future Directions: Confirmatory pragmatic RCTs across diverse settings and weight strata, evaluation of pathogen-specific risks, and stewardship implementation studies.
2. Plasma Extracellular Vesicle-Derived miR-296-5p is a Maturation-Dependent Rejuvenation Factor that Downregulates Inflammation and Improves Survival after Sepsis.
Plasma EVs from very young mice are cytoprotective and anti-inflammatory in sepsis, with miR-296-5p and miR-541-5p declining with age. Intraperitoneal miR-296-5p reduced mortality in murine sepsis, identifying a maturation-dependent rejuvenation factor with therapeutic potential.
Impact: Reveals a mechanistic, age-linked EV-miRNA axis that modulates inflammation and survival in sepsis, opening a path for miRNA-based therapeutics.
Clinical Implications: Although preclinical, miR-296-5p-based interventions may offer a novel immunomodulatory therapy, particularly relevant for older patients with heightened inflammatory responses.
Key Findings
- Young mouse plasma EVs are cytoprotective, anti-inflammatory, and reduce senescence markers in sepsis.
- EV miR-296-5p and miR-541-5p levels decline with age in plasma and multiple organs.
- Intraperitoneal miR-296-5p administration reduced mortality in a mouse sepsis model.
Methodological Strengths
- Integration of EV profiling with microRNA sequencing and functional in vitro/in vivo assays
- Use of clinically relevant polymicrobial sepsis model (CLP) alongside mechanistic validation
Limitations
- Preclinical mouse data; human translational relevance requires validation
- Dosing, delivery route (intraperitoneal), and off-target effects need optimization and safety evaluation
Future Directions: Translate EV-miRNA therapy toward clinical studies, define pharmacokinetics and delivery systems, and stratify by age-related inflammatory phenotypes.
3. Red Blood Cell-Induced Bacterial Margination Improves Microbial Hemoadsorption on Engineered Cell-Depleted Thrombi, Restoring Severe Bacteremia in Rats.
A microfluidic extracorporeal device leverages RBC-induced bacterial margination and engineered cell-depleted thrombi displaying bacterial adhesin receptors to remove intact bacteria from whole blood. In rat models of severe bacteremia, the approach restored bacterial control, indicating a broadly applicable hemoadsorption strategy.
Impact: Introduces a mechanistically novel, potentially universal platform for extracorporeal bacterial removal, addressing a longstanding limitation in hemoadsorption for sepsis.
Clinical Implications: If translated to humans, this technology could complement antibiotics in septic shock or refractory bacteremia by rapidly debulking circulating pathogens, particularly when multidrug resistance or slow antimicrobial kinetics limit efficacy.
Key Findings
- A novel extracorporeal device removes diverse intact bacteria from whole blood via microfluidic bacterial margination.
- Engineered cell-depleted thrombi (CDT) present bacterial adhesin receptors to enhance microbial capture.
- In rat severe bacteremia models, the system restored bacterial control, supporting therapeutic potential.
Methodological Strengths
- Innovative microfluidic design integrating biophysical margination and receptor-mediated capture
- In vivo validation in rat bacteremia, demonstrating functional efficacy
Limitations
- Preclinical rat data; human hemocompatibility, clotting, and safety not assessed
- Spectrum of pathogens and real-world blood flow/viscosity conditions require broader testing
Future Directions: Evaluate hemocompatibility and efficacy in large-animal models, define capture spectra and cartridge durability, and initiate first-in-human feasibility studies.