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.
BACKGROUND: Procalcitonin is a rapid response biomarker specific for bacterial infection, which is not routinely used in the UK National Health Service. We aimed to assess whether using a procalcitonin-guided algorithm would safely reduce the duration of antibiotic therapy compared with usual care, in which C-reactive protein is the commonly used biomarker. METHODS: The BATCH trial was a pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled trial conducted in 15 hospitals in England and Wales. Children aged 72 h to 18 years who were admitted to hospital and were being treated with intravenous antibiotics for suspected or confirmed bacterial infection and who were expected to remain on intravenous antibiotics for more than 48 h were enrolled. Participants were randomly assigned (1:1) to receive either current clinical management alone (usual care group) or clinical management with the addition of a procalcitonin test guided algorithm (procalcitonin group). Participants were randomly assigned by minimisation, with site and age group (0-6 months, 6 months to 2 years, 2-5 years, and older than 5 years) as minimisation factors and a random element to reduce predictability. Participants were randomly assigned remotely using a secure 24 h web-based randomisation programme. The coprimary outcomes were duration of intravenous antibiotic use, assessed for superiority, and a composite safety measure, assessed for non-inferiority (non-inferiority margin 5%). The primary analysis sample for each coprimary endpoint included all randomly assigned participants with available outcome data. This trial is registered with the International Standard Randomised Controlled Trial Number registry, ISRCTN11369832. FINDINGS: Between June 11, 2018, and Oct 12, 2022, 15 282 children were screened for eligibility, 1949 of whom were randomly assigned to receive procalcitonin-guided antibiotic therapy (n=977) or usual care (n=972). The median intravenous antibiotic duration was 96·0 h (IQR 59·5-155·5) in the procalcitonin group and 99·7 h (61·2-153·8) in the usual care group (hazard ratio 0·96 [95% CI 0·87-1·05]). 78 (9%) of 917 participants in the procalcitonin group and 85 (9%) of 904 participants in the usual care group had at least one event covered by the composite safety outcome measure (estimated adjusted risk difference -0·81% [95% CI upper bound 1·11]). INTERPRETATION: In children with suspected or confirmed bacterial infection admitted to hospitals in England and Wales for intravenous antibiotic treatment of at least 48 h, the introduction of a procalcitonin-guided algorithm did not reduce duration of intravenous antibiotics treatment and is non-inferior to usual care for safety outcomes. Therefore, evidence does not support the use of procalcitonin-guided algorithms where robust effective paediatric antibiotic stewardship programmes are established. FUNDING: National Institute for Health and Care Research.
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.
BACKGROUND: Patients with sepsis in the intensive care unit (ICU) often experience rapid muscle loss. The urea-to-creatinine ratio (UCR) is thought to reflect muscle breakdown (creatinine) and catabolism (urea) and is commonly used to assess nutritional and metabolic status. This study aimed to investigate whether changes in UCR (ΔUCR) can predict the development of rapid muscle loss in patients with sepsis. METHODS: This retrospective observational study was conducted in a university ICU between 2014 and 2021, involving adult patients (≥ 18 years) diagnosed with sepsis. The primary outcome was the incidence of rapid muscle loss during ICU hospitalization. Changes in the cross-sectional muscle area at the third lumbar vertebra (L3SMA) were measured using CT images to evaluate muscle loss. Rapid muscle loss was defined as a change in ΔL3SMA greater than 2% per day. Multivariable logistic regression was used to examine the association between UCR or ΔUCR and rapid muscle loss. The area under the receiver operating characteristic curve (AUC) was calculated to assess the predictive performance of UCR or ΔUCR for rapid muscle loss. RESULTS: Of the 482 patients, 141 (29.2%) experienced rapid muscle loss during their ICU stay. Multivariable logistic regression analysis revealed that ΔUCR was significantly associated with an increased risk of rapid muscle loss, with an odds ratio (OR) of 1.02 [95% CI: 1.01, 1.02]. The AUC for ΔUCR in predicting rapid muscle loss was 0.76 [95% CI: 0.68-0.83], with a threshold value of 19.4 µmol urea/µmol creatinine for ΔUCR. CONCLUSION: The results demonstrate that ΔUCR is independently associated with rapid muscle loss in patients with sepsis and the AUC of the ROC curve for the ability of ΔUCR to predict rapid muscle loss was 0.76. Though additional prospective data are needed, our results suggest that ΔUCR may be useful in the early identification of critically ill patients with sepsis at risk of rapid muscle loss.
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.
This study aimed to use meta-analytic techniques to evaluate aspirin's safety and effectiveness in treating elderly patients with sepsis. We searched PubMed, Embase, The Cochrane Library, Web of Science and Medline databases for relevant literature, screened and extracted key data and Stata 12.0 was used for comprehensive analysis. From library establishment to June 2024, relevant literature on aspirin for elderly sepsis patients was retrieved from PubMed, Web of Science, Embase, Medline and The Cochrane Library. Literature for meta-analysis was screened by inclusion and exclusion criteria and valid data was extracted. Stata 12.0 software was then used for integrated analysis. Finally, a total of 12 relevant pieces of literature were included in this study, involving 136,931 research subjects. The results of the meta-analysis showed that aspirin can reduce ICU mortality, in-hospital mortality, 30-day and 90-day mortality and the incidence of bleeding events in elderly patients with sepsis. It can also shorten the length of ICU stay but can not improve the incidence of organ failure. These suggest that aspirin has good efficacy and safety in the treatment of elderly patients with sepsis.