Daily Sepsis Research Analysis
A large pragmatic pediatric RCT found that a procalcitonin-guided algorithm did not shorten intravenous antibiotic duration and was non-inferior for safety compared with usual care. A single-center cohort linked early changes in the urea-to-creatinine ratio to rapid muscle loss in sepsis. A meta-analysis suggests aspirin may reduce mortality and ICU stay in elderly sepsis patients, but findings are likely confounded and call for RCTs.
Summary
A large pragmatic pediatric RCT found that a procalcitonin-guided algorithm did not shorten intravenous antibiotic duration and was non-inferior for safety compared with usual care. A single-center cohort linked early changes in the urea-to-creatinine ratio to rapid muscle loss in sepsis. A meta-analysis suggests aspirin may reduce mortality and ICU stay in elderly sepsis patients, but findings are likely confounded and call for RCTs.
Research Themes
- Antibiotic stewardship and biomarker-guided therapy in pediatric infections
- Metabolic biomarkers predicting rapid muscle loss in sepsis
- Adjunctive antiplatelet therapy signals in elderly sepsis (hypothesis-generating)
Selected Articles
1. Procalcitonin-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection in the UK (BATCH): a pragmatic, multicentre, open-label, two-arm, individually randomised, controlled trial.
In a multicentre pragmatic RCT of 1,949 hospitalized children, a procalcitonin-guided algorithm did not shorten the duration of IV antibiotics versus usual care and was non-inferior for safety. The findings argue against routine use of procalcitonin-guided algorithms where robust pediatric stewardship is in place.
Impact: This is the largest pragmatic pediatric RCT testing procalcitonin-guided therapy against contemporary stewardship, delivering definitive negative evidence that can immediately inform guidelines and policy.
Clinical Implications: Do not implement procalcitonin-guided algorithms solely to reduce IV antibiotic duration in pediatric inpatients where strong stewardship exists; maintain current stewardship-based decision-making.
Key Findings
- No reduction in IV antibiotic duration: median 96.0 h (PCT) vs 99.7 h (usual care); HR 0.96 (95% CI 0.87–1.05).
- Safety was non-inferior: composite adverse events in 9% vs 9%; adjusted risk difference −0.81% (95% CI upper bound 1.11, below 5% margin).
- Pragmatic, multicentre RCT across 15 hospitals randomizing 1,949 children using minimisation with age and site.
Methodological Strengths
- Pragmatic multicentre randomized design with clear co-primary endpoints (superiority and non-inferiority).
- Minimisation randomisation and trial registration with predefined non-inferiority margin.
Limitations
- Open-label design could influence clinician behavior despite objective primary outcome.
- Findings reflect UK settings with strong stewardship and may not generalize to regions with different practices; focus on IV duration may not capture total antibiotic exposure.
Future Directions: Evaluate procalcitonin or combined biomarker algorithms in settings with less mature stewardship, and identify subgroups (e.g., severe sepsis, immunocompromised) where biomarker guidance may add value.
2. Early urea-to-creatinine ratio to predict rapid muscle loss in critically ill patients with sepsis: a single-center retrospective observational study.
In 482 adults with sepsis, early changes in the urea-to-creatinine ratio (ΔUCR) independently predicted rapid muscle loss defined by CT-derived L3 muscle area decline >2% per day. ΔUCR achieved an AUC of 0.76 with a threshold of 19.4 µmol urea/µmol creatinine, suggesting a practical early warning biomarker.
Impact: Links a widely available laboratory ratio to objective CT-based sarcopenia metrics in ICU sepsis, providing a feasible tool to triage patients for early nutrition and rehabilitation.
Clinical Implications: Serially monitor UCR changes in ICU sepsis to flag patients at risk of rapid muscle loss and trigger early nutrition, mobilization, and potential anabolic strategies; consider confirmatory imaging when ΔUCR exceeds threshold.
Key Findings
- Rapid muscle loss occurred in 29.2% (141/482) of septic ICU patients.
- ΔUCR independently associated with rapid muscle loss: OR 1.02 (95% CI 1.01–1.02).
- Predictive performance for ΔUCR: AUC 0.76 (95% CI 0.68–0.83); threshold 19.4 µmol urea/µmol creatinine.
Methodological Strengths
- Objective quantification of muscle loss using CT-derived L3 cross-sectional area.
- Multivariable logistic regression with threshold determination and ROC analysis.
Limitations
- Single-center retrospective design with potential residual confounding and selection bias.
- UCR is influenced by renal function and catabolic state; generalizability beyond the studied ICU population is uncertain.
Future Directions: Prospectively validate ΔUCR thresholds across centers, integrate with functional measures (e.g., ultrasound, handgrip), and test whether ΔUCR-guided interventions mitigate ICU-acquired weakness.
3. A meta-analysis of the efficacy and safety of aspirin in the treatment of elderly patients with sepsis.
Across 12 studies including 136,931 elderly sepsis patients, aspirin use was associated with lower ICU, in-hospital, 30-day, and 90-day mortality, fewer bleeding events, and shorter ICU stay, without affecting organ failure incidence. Given likely observational designs and confounding, the findings are hypothesis-generating and warrant randomized trials.
Impact: The meta-analysis aggregates a large elderly sepsis population, signaling potential mortality benefit and acceptable safety with aspirin, which could redirect research toward mechanistic and randomized evaluations.
Clinical Implications: Do not change practice based on these results alone; if aspirin is used for other indications in elderly sepsis, clinicians should weigh bleeding risk and monitor closely. Prioritize enrollment in randomized trials evaluating low-dose aspirin as adjunctive therapy.
Key Findings
- Included 12 studies with a total of 136,931 elderly sepsis patients.
- Aspirin use associated with reduced ICU, in-hospital, 30-day, and 90-day mortality.
- Associated with fewer bleeding events and shorter ICU length of stay; no improvement in organ failure incidence.
Methodological Strengths
- Large aggregated sample size across multiple databases with meta-analytic synthesis.
- Comprehensive literature search across PubMed, Embase, Cochrane Library, Web of Science, and Medline.
Limitations
- Likely dominated by observational studies with residual confounding and selection bias; risk-of-bias and heterogeneity not detailed.
- Counterintuitive reduction in bleeding events with aspirin raises concerns about confounding and outcome definitions.
Future Directions: Conduct adequately powered randomized controlled trials of low-dose aspirin in elderly sepsis, with standardized bleeding definitions and organ dysfunction endpoints; explore mechanistic platelet–immune interactions.