Daily Sepsis Research Analysis
Analyzed 45 papers and selected 3 impactful papers.
Summary
Analyzed 45 papers and selected 3 impactful articles.
Selected Articles
1. Procalcitonin to Guide 7 vs 14 Days of Antibiotics in Bloodstream Infections: A Secondary Analysis of the BALANCE Trial.
In this planned secondary analysis of the BALANCE RCT, a day-7 procalcitonin level ≥250 pg/mL was associated with higher 90-day mortality, yet extending antibiotics from 7 to 14 days did not reduce mortality among those with elevated PCT. Seven days of therapy appears sufficient for most bloodstream infections irrespective of day-7 PCT.
Impact: Challenges the practice of prolonging antibiotics based on residual PCT levels and strengthens stewardship by supporting 7-day courses in bacteremia.
Clinical Implications: Avoid extending antibiotic therapy beyond 7 days solely due to elevated day-7 PCT in stable bloodstream infection patients; prioritize clinical stability and source control over biomarker-driven prolongation.
Key Findings
- Day-7 PCT ≥250 pg/mL was associated with higher 90-day mortality (21.6% vs 6.2%; ARD 15.5%, 95% CI 3.6–27.5).
- Among high PCT patients, 7 vs 14 days of antibiotics showed no difference in 90-day mortality.
- Seven days of antibiotics appears sufficient for most bloodstream infections regardless of day-7 PCT.
Methodological Strengths
- Nested within a multicenter RCT with standardized follow-up and blinded biomarker measurement.
- Prespecified secondary analysis framework with clinically relevant outcomes (90-day mortality).
Limitations
- Modest sample size (n=125) may limit precision and subgroup analyses.
- Observational nature of the PCT-mortality association within the RCT; potential residual confounding.
Future Directions: Prospective trials to test biomarker-guided early discontinuation strategies and evaluate whether combined clinical-PCT algorithms can safely shorten therapy further.
IMPORTANCE: The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) trial showed that 7 days of antibiotics was noninferior to 14 days among patients with bacteremia. However, it is unknown whether patients with high serum procalcitonin (PCT) level at day 7 of therapy would benefit from a prolonged treatment course. OBJECTIVE: To investigate whether an elevated serum PCT level at day 7 of bacteremia was associated with increased mortality among patients treated with 7 vs 14 days of antibiotics. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a planned secondary analysis of the BALANCE trial from 2014 to 2023, a multicenter randomized clinical trial where serum was collected on day 7 of bacteremia and patients were followed up for 90 days after study enrollment. Serum samples were collected from patients 7 days after initiation of antibiotics; PCT levels were later quantified by an antibody-based assay and therefore were not available to clinicians. Data were analyzed from January to June 2025. INTERVENTION: Patients were randomized to receive either 7 or 14 days of antibiotics. Antibiotic selection, dosing, and route were at the discretion of the treating team. MAIN OUTCOMES AND MEASURES: The primary outcome was defined as death from any cause within 90 days of the positive index blood culture result. Secondary outcomes included death by any cause while admitted to the ICU, death by any cause while admitted to the hospital, number of days alive and not admitted to the ICU within 28 days of the index positive blood culture, number of days alive and not admitted to hospital within 28 days of the index positive blood culture, and the duration of mechanical ventilation. RESULTS: A total of 125 patients (median age 63, [IQR, 58-79] years; 80 [64.0%] male) were included in this study. Sixty-five participants (52%) had low PCT levels (<250 pg/mL) and 60 (48%) had high PCT levels (≥250 pg/mL) on day 7. The high PCT group was older, had more comorbidities, and had a higher prevalence of community-acquired bacteremia. Ninety-day mortality was higher in the high vs low PCT group: 21.6% (13 of 60) vs 6.2% (4 of 65) (absolute risk difference [ARD] 15.5%; 95% CI, 3.6%-27.5%). Among patients with high PCT level, 90-day mortality was not different among participants with 7 vs 14 days of antbiotics (ARD, -19.9%; 95% CI, -1.7 to 41.7). CONCLUSIONS AND RELEVANCE: In this cohort study, elevated PCT level on day 7 was associated with increased 90-day mortality. However, prolonging antibiotics beyond 7 days was not associated with improved mortality in patients with a residually high PCT level. Seven days of antibiotics appears sufficient for most patients with bloodstream infections independent of day 7 serum PCT level.
2. Effect of needle disinfection with different antiseptic agents on infectious complications after TRUS-guided prostate biopsy: a prospective randomized study.
In a randomized single-center trial (n=240), dipping the biopsy needle in 10% formalin after each core during TRUS-guided prostate biopsy eliminated febrile events, hospitalizations, and sepsis, outperforming povidone-iodine and isopropyl alcohol. Needle disinfection meaningfully reduced post-procedural infections compared with no disinfection.
Impact: Simple intra-procedural disinfection eliminated sepsis events in this trial, offering an immediately actionable measure to reduce procedure-related infections.
Clinical Implications: Consider implementing 10% formalin needle disinfection after each core during TRUS biopsy where feasible, while evaluating local safety protocols and alternatives (e.g., povidone-iodine) and monitoring for long-term safety.
Key Findings
- Non-disinfection had the highest febrile UTI rate (11.6%).
- Formalin (10%) group had zero fever, hospitalization, or sepsis cases.
- Povidone-iodine and isopropyl alcohol reduced infections versus no disinfection but were less effective than formalin.
Methodological Strengths
- Prospective randomized design with direct clinical endpoints (fever, hospitalization, sepsis).
- Trial preregistration (ClinicalTrials.gov NCT06836271).
Limitations
- Single-center study with short follow-up; generalizability and long-term safety are uncertain.
- Formalin exposure and workflow feasibility may vary across settings.
Future Directions: Multicenter trials with longer follow-up to confirm safety, evaluate microbiologic outcomes, and compare disinfection protocols across diverse settings.
BACKGROUND: Transrectal ultrasound-guided prostate biopsy (TRUS-guided biopsy) remains widely used for the diagnosis of prostate cancer, but it is associated with a risk of infectious complications despite antibiotic prophylaxis. OBJECTIVES: To evaluate the effect of disinfecting the prostate biopsy needle with different antiseptic agents after each core sampling on post-procedural infectious complications. DESIGN: A prospective, randomized, single-center clinical study. METHODS: Between February and May 2025, 240 patients undergoing TRUS-guided prostate biopsy were randomly assigned to four groups ( RESULTS: The rate of febrile urinary tract infection was highest in the non-disinfection group (11.6%). No cases of fever, hospitalization, or sepsis were observed in the formalin group. Povidone-iodine and isopropyl alcohol disinfection were associated with lower infection rates than no disinfection, but were less effective than formalin. CONCLUSION: Disinfection of the biopsy needle after each core sampling is associated with a meaningful reduction in infectious complications following TRUS-guided prostate biopsy. Among the evaluated agents, 10% formalin demonstrated the greatest protective effect; however, further multicenter studies with longer follow-up are required to confirm long-term safety and generalizability. TRIAL REGISTRATION: This trial was prospectively registered at ClinicalTrials.gov (Identifier: NCT06836271; Local trial ID: HititUrology001).
3. MicroRNAs in sepsis diagnosis: A systematic review and meta-analysis toward evidence-based biomarker development.
Across 39 studies, circulating microRNAs showed pooled sensitivity 0.79 and specificity 0.82 (AUROC 0.87) for sepsis diagnosis, but with substantial heterogeneity. Functional subgroup analyses suggest performance depends on both miRNA biology and methodological choices, underscoring the need for standardized, clinically grounded designs.
Impact: Provides an updated, methodologically explicit synthesis of miRNA diagnostic performance, moving the field toward pathway-specific panels and standardized evaluation.
Clinical Implications: miRNA panels may complement existing biomarkers for sepsis triage, but current heterogeneity precludes routine use; standardized assays and validation against infected non-septic controls are prerequisites.
Key Findings
- Pooled diagnostic performance: sensitivity 0.79, specificity 0.82, AUROC 0.87 across 39 studies (59 miRNAs).
- Substantial between-study heterogeneity; performance varied by functional miRNA subgroups and methodological factors.
- Calls for standardized protocols and clinically relevant control groups to establish clinical utility.
Methodological Strengths
- PRISMA 2020 and PRISMA-DTA–compliant systematic review with QUADAS-2 quality appraisal.
- Use of HSROC modeling and prespecified subgroup analyses to explore heterogeneity.
Limitations
- High heterogeneity and variable reference standards limit generalizability.
- Many studies used suboptimal controls (e.g., healthy) rather than infected non-septic comparators.
Future Directions: Prospective multicenter studies using standardized miRNA panels, harmonized pre-analytics, and infected non-septic controls to validate pathway-specific diagnostic tools.
BACKGROUND: Sepsis diagnosis remains challenging, and conventional biomarkers such as CRP and PCT show limited specificity. Circulating microRNAs (miRNAs) have been investigated as diagnostic biomarkers, but substantial methodological variability across studies has limited the interpretation of current evidence. Previous meta-analyses largely evaluated miRNAs as a single biomarker category, leaving variation across biologically distinct subgroups insufficiently explored. METHODS: Following PRISMA 2020 and PRISMA-DTA 2018 guidelines, we systematically searched PubMed, EMBASE, and Scopus through April 2026. Study quality was assessed using QUADAS-2, and pooled diagnostic performance was analyzed using a hierarchical summary receiver operating characteristic (HSROC) model. Subgroup analyses explored clinical, methodological, and functional sources of heterogeneity. RESULTS: Thirty-nine studies involving 59 distinct miRNAs were included. Pooled sensitivity was 0.79 (95% CI: 0.76-0.82) and specificity was 0.82 (95% CI: 0.78-0.85), with an AUROC of 0.87 (95% CI: 0.84-0.90). Substantial heterogeneity was observed (sensitivity I CONCLUSION: Circulating miRNAs demonstrate moderate diagnostic accuracy for sepsis, with functional subgroup analyses showing differences across biologically distinct miRNA categories. Diagnostic performance appears to vary according to both biological function and methodological context. Substantial heterogeneity limits the generalizability of current evidence. Future multicenter studies using standardized protocols and infected non-septic control groups are needed to determine the clinical utility of pathway-specific miRNA panels.