Daily Sepsis Research Analysis

GOALS: To evaluate whether prophylactic antibiotics improve infectious complication rates after endoscopic retrograde cholangiopancreatography (ERCP). BACKGROUND: Current guidelines recommend prophylactic antibiotics before ERCP only in cases of anticipated incomplete biliary drainage or severe immunosuppression. A recent randomized controlled trial (RCT) suggested a benefit regardless of drainage status. This systematic review and meta-analysis assess the impact of prophylactic antibiotics on post-ERCP infectious complications. STUDY: A systematic search of major databases was conducted through June 2024 for RCTs comparing ERCP outcomes with and without antibiotic prophylaxis. Pooled data were analyzed for the composite outcome of infectious complications, including cholangitis, bacteremia, and sepsis. Mortality and pancreatitis were also analyzed. Publication bias was evaluated using funnel plots and regressions for funnel plot asymmetry. Our analysis implemented a dichotomous regression model with random effects using R software. RESULTS: Eleven RCTs with 2105 patients were included, with 1086 receiving antibiotics and 1019 serving as controls. Infectious complications were significantly lower in the antibiotic group [risk difference (RD): -0.08, 95% CI: -0.14 to -0.02, P=0.00001, I2: 83%]. Beta-lactam and cephalosporin antibiotics had a greater effect (RD: -0.10, 95% CI: -0.17 to -0.04, P=0.00001, I2: 85%). Bacteremia rates were also reduced (RD: -0.06, 95% CI: -0.11 to -0.01, P=0.01, I2: 58%). No significant differences were found in cholangitis, sepsis, pancreatitis, or mortality. Sensitivity analyses confirmed robustness. CONCLUSIONS: Antibiotic prophylaxis reduces post-ERCP infectious complications and should be considered in all patients with biliary obstruction who are undergoing ERCP.

BACKGROUND: Timely and accurate identification of bloodstream pathogens is critical for targeted antimicrobial therapy in sepsis. Conventional blood cultures remain the Standard-of-Care (SoC) for pathogen identification but are limited by low sensitivity and prolonged turnaround times, hampering timely and targeted antimicrobial stewardship. Advances in next-generation sequencing (NGS) offer potential for culture-independent, rapid, and comprehensive detection of pathogens and prediction of antimicrobial resistance. This study evaluated the diagnostic performance of PISTE™ technology, an NGS-based diagnostic workflow combining full-length 16S rRNA gene sequencing and metagenomic analysis for the diagnosis of circulating bacteria in sepsis. METHODS: In this prospective, multicenter, phase IIa proof-of-concept study, adult patients with suspected sepsis were enrolled from four hospitals in Athens, Greece. Blood samples were collected prior to antibiotic initiation and processed using SoC cultures and PISTE platform. PISTE integrates automated DNA purification (KingFisher, Thermo Fisher Scientific), full-length 16S rRNA gene sequencing, metagenomics analysis (SQK-PRB114.24, Oxford Nanopore Technologies), and real-time sequencing using Oxford Nanopore GridION Mk1b device. A dedicated analysis pipeline was developed for accurate pathogen detection and prediction of antimicrobial resistance profiles. The primary endpoint was the diagnostic concordance between PISTE and SoC cultures. RESULTS: A total of 100 patients (median age 79 years, median Charlson's Comorbidity Index 5) were enrolled. Of these, 71 patients met Sepsis-3 criteria. In this subgroup, PISTE showed an overall accuracy of 95.7%, with a sensitivity of 91.7%, specificity of 96.5%, positive predictive value of 84.6%, and negative predictive value of 98.2% compared to SoC. The median time to pathogen identification and Antimicrobial Susceptibility Testing (AST) with PISTE was 12.0 hours, significantly faster than in SoC cultures (30.4 hours, p < 0.0001). Resistance gene profiling showed strong agreement with SoC AST results, particularly for β-lactam and carbapenem resistance. CONCLUSIONS: PISTE technology exhibited high diagnostic accuracy and significantly reduced turnaround time compared to conventional cultures, supporting its potential as a short turnaround time and reliable diagnostic tool for bloodstream infections. Further optimization and validation in larger cohorts are warranted to enhance clinical implementation and improve antimicrobial stewardship in sepsis management.

BACKGROUND: The best blood pressure target in sepsis is a matter of debate. SEPSIS-PAM, a large multicenter pragmatic randomized controlled trial, compared two mean arterial pressure targets (65-70 mmHg vs 80-85 mmHg) in septic shock and did not find any difference in mortality. The goal of this study was to assess whether (i) heterogeneity of treatment effect (HTE) exists in the response to different targets and (ii) the initial clinical trajectory can inform the optimal blood pressure target. METHODS: The primary outcome was mortality at day 28. Secondary outcomes included mortality at day 90, acute kidney injury (AKI), and severe AKI based on the KDIGO classification, need for renal replacement therapy, renal replacement therapy, and vasopressor-free days. The presence of HTE was tested for and, if present, quantified. The interaction between post-randomization evolution of the MAP, norepinephrine requirements, lactate, mottling score, and urine output was estimated using a multimediation analysis. RESULTS: 776 patients were enrolled and analyzed in this study. There was no evidence of significant treatment effect heterogeneity based on baseline characteristics (sweep p-value = 0.664; 95% CI: 0.633-0.673). The direct effect of a higher MAP target on mortality, holding 24 h mediators at their control-level values, was not significant (RD = 0.017; 95% CI - 0.052 to 0.086; p = 0.62). However, if reaching a higher MAP required high norepinephrine doses and/or did not result in mottled skin resolution at 24 h, the effect transmitted through those mediators was associated with higher mortality (risk difference = 0.027; 95% CI 0.012-0.047 and 0.012; 95% CI 0.001-0.026). CONCLUSION: Our results suggest the absence of heterogeneity of the response to different blood pressure targets in patients with septic shock. Targeting a higher MAP target may be associated with harm when high norepinephrine doses are required or when mottled skin is present. TRIAL REGISTRATION: SEPSISPAM ClinicalTrials.gov number, NCT01149278.