Daily Sepsis Research Analysis
Three papers stand out today: a meta-analysis shows prophylactic antibiotics reduce infectious complications in ERCP for biliary obstruction; a prospective multicenter study demonstrates an NGS-based, culture-independent workflow that identifies bloodstream pathogens and resistance within 12 hours; and a post hoc analysis of a septic shock RCT indicates potential harm from targeting higher MAP when high norepinephrine doses are required or mottling persists.
Summary
Three papers stand out today: a meta-analysis shows prophylactic antibiotics reduce infectious complications in ERCP for biliary obstruction; a prospective multicenter study demonstrates an NGS-based, culture-independent workflow that identifies bloodstream pathogens and resistance within 12 hours; and a post hoc analysis of a septic shock RCT indicates potential harm from targeting higher MAP when high norepinephrine doses are required or mottling persists.
Research Themes
- Periprocedural infection prevention in biliary interventions
- Rapid culture-independent sepsis diagnostics and antimicrobial stewardship
- Individualized hemodynamic targets in septic shock
Selected Articles
1. Is Antibiotic Prophylaxis Warranted in All Patients With Biliary Obstruction Undergoing Endoscopic Retrograde Cholangiopancreatography?: A Systematic Review and Meta-Analysis.
Across 11 RCTs (n=2105), antibiotic prophylaxis before ERCP for biliary obstruction reduced composite infectious complications and bacteremia, with stronger effects for beta-lactams/cephalosporins. No significant differences were observed for cholangitis, sepsis, pancreatitis, or mortality.
Impact: Synthesizing RCT evidence, this analysis challenges restrictive guideline criteria and supports broader prophylaxis in biliary obstruction ERCP to prevent serious infections.
Clinical Implications: Consider routine antibiotic prophylaxis for patients with biliary obstruction undergoing ERCP, prioritizing beta-lactam/cephalosporin regimens, while balancing local resistance patterns.
Key Findings
- Included 11 RCTs with 2,105 patients; 1,086 received antibiotics, 1,019 controls
- Antibiotic prophylaxis reduced composite infectious complications (RD -0.08; 95% CI -0.14 to -0.02)
- Beta-lactam/cephalosporin regimens showed larger effects (RD -0.10; 95% CI -0.17 to -0.04)
- Bacteremia was reduced (RD -0.06; 95% CI -0.11 to -0.01)
- No significant differences in cholangitis, sepsis, pancreatitis, or mortality; results robust in sensitivity analyses
Methodological Strengths
- Randomized controlled trials only with random-effects meta-analysis
- Assessment of publication bias and sensitivity analyses performed
Limitations
- High between-study heterogeneity for composite infections (I2=83%)
- No significant reduction in sepsis or mortality; antibiotic regimens varied across trials
Future Directions: Define optimal antibiotic classes, dosing, and timing; evaluate impact on antimicrobial resistance and cost-effectiveness; stratify by drainage completeness and immunosuppression.
2. An NGS-assisted diagnostic workflow for culture-independent detection of bloodstream pathogens and prediction of antimicrobial resistances in sepsis.
In a prospective multicenter study, the PISTE NGS workflow achieved 95.7% accuracy versus SoC in Sepsis-3 patients, with sensitivity 91.7% and specificity 96.5%, and cut the time to organism and resistance profiling to 12 hours from 30.4 hours. Resistance gene calls aligned well with phenotypic AST, especially for beta-lactam and carbapenem resistance.
Impact: Demonstrates a practical, culture-independent diagnostic that accelerates pathogen and resistance detection, enabling earlier targeted therapy and improved antimicrobial stewardship.
Clinical Implications: Adopting rapid NGS workflows could shorten empiric therapy windows, reduce broad-spectrum antibiotic exposure, and improve time-to-effective therapy in suspected sepsis.
Key Findings
- Prospective, multicenter phase IIa diagnostic accuracy study (n=100; 71 met Sepsis-3)
- Accuracy 95.7%, sensitivity 91.7%, specificity 96.5%, PPV 84.6%, NPV 98.2% vs. SoC
- Median turnaround for ID+AST was 12.0 hours vs. 30.4 hours with cultures (p<0.0001)
- Resistance gene profiling agreed with SoC AST, especially β-lactam/carbapenem resistance
- Blood samples collected prior to antibiotics; integrated full-length 16S and metagenomics on nanopore platform
Methodological Strengths
- Prospective multicenter enrollment with head-to-head comparison to SoC cultures
- Pre-antibiotic sampling and defined diagnostic accuracy metrics including TAT
Limitations
- Phase IIa proof-of-concept with modest sample size and single-country sites
- Clinical impact on outcomes (e.g., mortality, length of stay) not tested
Future Directions: Scale-up validation across diverse settings, integrate with stewardship workflows, and perform impact trials assessing time-to-effective therapy and clinical outcomes.
3. Heterogeneity in the response to a high vs low mean arterial pressure target in patients with septic shock a post hoc analysis of a randomized controlled trial.
Post hoc analysis of 776 septic shock patients found no baseline-driven heterogeneity in response to MAP targets. Mediation analyses indicated potential harm from higher MAP targets when achieving them required high norepinephrine doses and/or when mottling persisted at 24 hours.
Impact: Provides nuanced evidence to individualize blood pressure targets, discouraging pursuit of higher MAP when vasopressor burden is high or perfusion signs (mottling) fail to improve.
Clinical Implications: Avoid routine targeting of MAP 80–85 mmHg if it requires high norepinephrine doses or if mottling persists; consider dynamic perfusion markers and vasopressor burden when setting MAP goals.
Key Findings
- No significant heterogeneity of treatment effect based on baseline characteristics (sweep p=0.664)
- Direct effect of higher MAP on 28-day mortality was not significant (RD 0.017; p=0.62)
- Higher MAP associated with increased mortality when mediated by high norepinephrine doses (RD 0.027) and/or persistent mottling at 24 h (RD 0.012)
- Mediation framework incorporated MAP trajectory, norepinephrine, lactate, mottling, and urine output
Methodological Strengths
- Secondary analysis of a large multicenter pragmatic RCT dataset
- Advanced multimediation approach linking post-randomization trajectories to outcomes
Limitations
- Post hoc nature limits causal inference; findings are hypothesis-generating
- Mediator variables are post-randomization and may be influenced by unmeasured confounders
Future Directions: Prospective trials testing MAP strategies guided by perfusion signs and vasopressor thresholds; integration of bedside mottling and vasopressor dose into decision algorithms.