Sepsis, November 5 edition

This systematic review and meta-analysis included 75 studies involving 26,377 patients with Gram-negative bacterial infections. The pooled bloodstream infection incidence was 17.3%; inflammatory biomarkers, prior carbapenem exposure, mechanical ventilation, central venous catheterization, immunosuppression, and aminoglycoside use were important predictors, while hypoalbuminemia and urinary catheterization were particularly associated with carbapenem-resistant infections and continuous renal replacement therapy with Acinetobacter baumannii infection.

Impact: The study moves beyond generic sepsis risk prediction by separating shared predictors from resistance- and pathogen-specific signals. This distinction can support more targeted surveillance, empiric antimicrobial selection, and antimicrobial stewardship.

Clinical Implications: Patients with Gram-negative infections who have elevated procalcitonin or C-reactive protein, prior carbapenem exposure, mechanical ventilation, central venous access, or immunosuppression may warrant intensified blood-culture assessment and earlier consideration of resistant pathogens. Hypoalbuminemia, urinary catheterization, and continuous renal replacement therapy may help refine risk assessment for specific resistant or Acinetobacter phenotypes.

Future Directions: Future prospective multicenter studies should validate pathogen- and resistance-specific prediction models using standardized definitions and local epidemiologic calibration. Clinical utility trials should determine whether incorporating these factors into empiric antibiotic algorithms improves time to appropriate therapy without increasing unnecessary broad-spectrum antibiotic use.

The investigators developed NeutroDrop, a droplet microfluidic assay that quantifies oxidative and proteolytic functions of individual neutrophils. Sepsis was characterized by reduced neutrophil elastase activity and depletion of high-ROS/high-NE cells; a derived outcome index predicted 12-day survival with 83.33% sensitivity and 92.85% specificity in the discovery cohort, while blinded testing correctly classified all 10 operator-blinded samples and matched outcomes in 5 of 6 sepsis cases.

Impact: This study directly measures immune-cell functional heterogeneity rather than relying only on circulating concentrations or organ dysfunction scores. The integration of single-cell analysis, locked classification rules, and blinded testing provides an innovative translational framework for functional sepsis diagnostics.

Clinical Implications: NeutroDrop could eventually complement conventional sepsis assessment by identifying impaired neutrophil effector function and patients at high short-term mortality risk. It is not yet ready to replace established diagnostic criteria because the cohort was small and the assay requires technical validation, workflow integration, and prospective clinical testing.

Future Directions: Larger, multicenter prospective studies should compare NeutroDrop with established sepsis scores and biomarkers across bacterial, viral, and noninfectious inflammatory syndromes. Future work should assess analytical reproducibility, turnaround time, cost, automation, and whether functional neutrophil phenotyping can guide immunomodulatory or antimicrobial treatment decisions.

This population-based retrospective cohort included 296,554 sepsis admissions in Catalonia from 2005 to 2019, of whom 237,075 survived to discharge. Among survivors, 42% died within 2 years; mortality increased sharply with age and Charlson comorbidity burden, and neoplasia, cirrhosis, and dementia were major risk factors, demonstrating that sepsis survivorship carries a substantial continuing mortality burden.

Impact: The very large, population-based dataset quantifies the post-sepsis mortality burden across the full age spectrum and identifies clinically recognizable high-risk groups. These findings strengthen the rationale for structured post-sepsis follow-up rather than treating hospital discharge as the endpoint of recovery.

Clinical Implications: Post-sepsis programs should prioritize older adults and patients with substantial comorbidity, particularly malignancy, cirrhosis, or dementia. Follow-up should include medication review, functional and cognitive assessment, monitoring for recurrent infection and organ dysfunction, and coordination between intensive care, primary care, and specialty services.

Future Directions: Prospective multicenter studies should determine which post-sepsis interventions reduce late mortality and improve functional recovery. Future risk models should incorporate illness severity, frailty, socioeconomic factors, organ-specific sequelae, and patient-reported outcomes, followed by pragmatic trials of risk-stratified post-sepsis clinics.