Daily Sepsis Research Analysis
Precision medicine and diagnostics led today’s sepsis research. A secondary analysis of the ADRENAL RCT found no overall endotype-specific benefit of hydrocortisone in septic shock, but a harm signal in pulmonary sepsis with an adaptive-prevalent immune endotype. A nationwide cohort linked early-onset neonatal sepsis to increased autism risk, and a microchip assay showed high accuracy for detecting β-lactam resistance genes directly from positive blood cultures.
Summary
Precision medicine and diagnostics led today’s sepsis research. A secondary analysis of the ADRENAL RCT found no overall endotype-specific benefit of hydrocortisone in septic shock, but a harm signal in pulmonary sepsis with an adaptive-prevalent immune endotype. A nationwide cohort linked early-onset neonatal sepsis to increased autism risk, and a microchip assay showed high accuracy for detecting β-lactam resistance genes directly from positive blood cultures.
Research Themes
- Precision therapeutics and endotyping in septic shock
- Long-term neurodevelopmental outcomes after neonatal sepsis
- Rapid molecular diagnostics for antimicrobial resistance in bloodstream infection
Selected Articles
1. A gene expression-based approach for the precision use of hydrocortisone in septic shock patients; a secondary analysis of the ADRENAL trial.
Among 540 septic shock patients, gene expression-defined endotypes (IA-P vs IN-P) were roughly equal, and hydrocortisone showed no heterogeneity of treatment effect on 28-day mortality overall. In pulmonary sepsis, IA-P patients receiving hydrocortisone had higher mortality, suggesting potential harm in this subgroup.
Impact: This RCT-based endotyping analysis advances precision medicine in septic shock and flags a plausible harm signal for hydrocortisone in a biologically defined pulmonary sepsis subgroup.
Clinical Implications: Routine steroid use in septic shock may warrant re-evaluation in pulmonary sepsis with an adaptive-prevalent endotype; prospective, real-time endotyping to guide steroids should be tested before practice change.
Key Findings
- 540 septic shock patients were classified into IA-P (49.4%) and IN-P (50.6%) immune endotypes using predefined gene expression signatures.
- No overall heterogeneity of hydrocortisone effect on 28-day mortality between IA-P and IN-P (Bayesian OR ~1.4 with wide credible intervals).
- In pulmonary sepsis (n=232), IA-P patients treated with hydrocortisone had increased mortality (OR 5.55, 95% CrI 1.81–21.2).
- Severe shock subgroup analyses did not show endotype-specific differences in hydrocortisone effect.
Methodological Strengths
- Predefined gene expression signatures to classify immune endotypes
- Bayesian analysis and use of randomized trial cohort (ADRENAL) enhancing internal validity
Limitations
- Secondary analysis with potential for residual confounding and multiple comparisons
- Harm signal in pulmonary sepsis IA-P subgroup is based on subgroup analysis with limited sample and wide credible intervals
Future Directions: Prospective trials testing steroid strategies stratified by real-time endotyping, and mechanistic studies to elucidate why IA-P pulmonary sepsis might be harmed by corticosteroids.
2. Early-Onset Neonatal Infection and Attention Deficit Hyperactivity and Autism Spectrum Disorder: A Nationwide Cohort Study.
Among 981,869 children, early-onset sepsis was associated with increased risk of ASD (adjusted HR 1.43) and a modest increase for ADHD (HR 1.28) that attenuated in sibling-matched analyses (HR 1.12). Culture-confirmed cases were few, but findings suggest a neurodevelopmental signal primarily for ASD.
Impact: This very large, methodologically rigorous cohort with sibling controls links early neonatal sepsis to later autism risk, informing surveillance strategies and hypotheses on brain–immune interactions.
Clinical Implications: Children with early-onset neonatal sepsis may benefit from targeted developmental surveillance and early intervention pathways; prevention of neonatal invasive infections remains critical.
Key Findings
- Early-onset sepsis was associated with increased ASD risk (adjusted HR 1.43, 95% CI 1.30–1.58).
- Association with ADHD was weaker (HR 1.28, 95% CI 1.17–1.39) and attenuated in sibling-matched analyses (HR 1.12, 95% CI 0.93–1.34).
- Culture-positive sepsis and meningitis cases were few (sepsis n=257; meningitis n=32), with meningitis showing point estimates suggestive of increased risk but wide CIs.
Methodological Strengths
- Nationwide registry cohort with nearly one million participants and long follow-up
- Sibling-matched analyses to control for shared familial confounding
Limitations
- Observational design with potential residual confounding and misclassification from diagnosis codes
- Low number of culture-confirmed infections limits pathogen-specific inference
Future Directions: Replicate in other populations, integrate granular perinatal and infection severity data, and investigate mechanistic pathways linking neonatal inflammation to neurodevelopment.
3. Detection of β-lactam resistance genes in Gram-negative bacteria from positive blood cultures using a microchip-based molecular assay.
A microchip-based assay detected β-lactam resistance genes directly from positive blood cultures with high accuracy, correctly identifying 99.5% of target genes in simulated samples and showing broader gene coverage than BCID2. Clinical sample testing supports potential routine use, pending prospective validation.
Impact: Rapid genotypic resistance profiling directly from blood cultures could enable earlier targeted therapy and stewardship, particularly for Gram-negative sepsis.
Clinical Implications: Laboratories could complement or bridge phenotypic AST with rapid gene detection to guide early de-escalation/escalation; confirmatory phenotypic testing remains essential.
Key Findings
- The microchip assay correctly identified 203/204 (99.5%) β-lactam resistance genes in simulated GN positive blood culture samples.
- Demonstrated broader β-lactam resistance gene coverage compared with BCID2.
- Feasibility supported by testing in both simulated (n=146) and clinical (n=106) samples.
Methodological Strengths
- Direct-from-positive blood culture testing reduces time to genotypic results
- Head-to-head comparison indicating broader gene coverage than an established panel (BCID2)
Limitations
- Use of simulated samples may overestimate performance relative to real-world clinical diversity
- Clinical sample size was modest; genotype may not always predict phenotype
Future Directions: Prospective multicenter studies to quantify impact on time to effective therapy, clinical outcomes, and cost-effectiveness, and integration with stewardship workflows.