Daily Sepsis Research Analysis

BACKGROUND: Bloodstream infection (sepsis) represents a systemic inflammatory response to systemic infection by bacteria, fungi, and viruses that can lead to severe complications and death. The therapeutic management to reduce mortality and morbidity associated with sepsis is difficult due partly to (re)emergence of antimicrobial resistance. The choice of empirical antibiotics, therefore, partly depends on the pattern of local/national antibiotic resistance. This systematic review and meta-analysis aimed to determine the prevalence of bacteremia among pediatric patients with suspected bloodstream infections in Ethiopia, based on culture-confirmed bacterial isolates. METHODS: A comprehensive search of PubMed, Google Scholar, and grey literature was conducted for studies published between January 2010 and April 2024 on bacterial bloodstream infections and antimicrobial resistance. Laboratory-based observational studies reporting bacterial isolates and resistance patterns were included. Data from 23 eligible studies were extracted independently, organized in Excel, and analyzed using Stata version 14. Pooled prevalence estimates were calculated using a random-effects model. Heterogeneity was assessed via the I² statistic, publication bias through funnel plots and Egger's test, and sensitivity analysis evaluated the influence of individual studies. RESULTS: The pooled prevalence of bacterial bloodstream infections (BSIs) among pediatric patients in Ethiopia was 30.66% (95% CI: 27.18-34.15), underscoring a serious public health concern. The most frequently isolated pathogens were Klebsiella species (30.6%), coagulase-negative staphylococci (CoNS), and Staphylococcus aureus, with Gram-negative bacteria comprising 56.65% of isolates. The overall pooled prevalence of multidrug resistance (MDR) was alarmingly high at 80.54%, with 100% resistance observed in both Klebsiella and Acinetobacter species. Subgroup analyses revealed MDR rates of 81.9% in general wards, 78.35% in NICUs, 82.07% among children, and 78.86% among neonates. Regionally, MDR prevalence ranged from 76.7% in Tigray to 91.3% in Addis Ababa, Amhara, and Oromia-highlighting a critical challenge for sepsis treatment and antimicrobial stewardship in Ethiopian pediatric care settings. CONCLUSION: The findings underscore the urgent need for robust antimicrobial stewardship and enhanced surveillance to combat the growing threat of AMR in pediatric BSIs in Ethiopia. Strengthening routine antimicrobial susceptibility testing, improving healthcare infrastructure, and raising public awareness on responsible antibiotic use are critical. Targeted interventions are essential to guide effective treatment, prevent therapeutic failure, and reduce sepsis-related mortality.

Sepsis is a systemic inflammatory response syndrome caused by infection, which has a high morbidity and mortality. Short-chain fatty acids (SCFAs) have been proved to improve the outcome of sepsis by regulating immunity and metabolism, but its specific mechanism is not clear. This study employed a multi-omics strategy integrating murine models, untargeted metabolomics, human transcriptomics (GSE185263, GSE54514), single-cell RNA sequencing (GSE167363), and Mendelian randomization to investigate SCFAs' role in sepsis. Cecal ligation and puncture (CLP) was performed in C57BL/6 mice (n = 60). Transcriptomic analysis identified 76 differentially expressed genes between septic and healthy subjects. Machine learning (SVM-RFE and LASSO regression) prioritized five SCFA-associated hub genes (CASP5, GPR84, MMP9, MPO, PRTN3), with molecular docking revealing two potential modulators. Single-cell profiling localized these targets to monocytes, while immune infiltration analysis confirmed SCFA-mediated immunomodulation. Murine metabolomics identified glycerophospholipid (GPL) metabolism as the most significantly altered pathway under SCFAs intervention. Mendelian randomization established causal relationships between GPL pathway genes and sepsis incidence/28-day mortality. Collectively, the study provide novel mechanistic and translational insights into the therapeutic targeting of short-chain fatty acids in sepsis.

Haemoadsorption has been suggested as treatment adjunct for sepsis and septic shock, cardiac surgery, acute respiratory distress syndrome, and coronavirus disease 2019 (COVID-19). Randomised clinical trials did not provide conclusive evidence for benefits and even suggest risks in COVID-19 patients. Retrospective observational cohort study based on hospital remuneration data from all COVID-19 patients treated in intensive care units in Germany between 01/01/2020 and 12/31/2021. Regression modelling was performed for 1:1 propensity score matching of 2058 patients. Two-sided probability values for group comparisons and regression models with spline functions controlling for non-linear relationships and medically relevant interaction variables were calculated. In-hospital mortality of patients supported with haemoadsorption was significantly higher compared to matched control patients (74.6% vs. 70.3%, p = 0.0299). Haemoadsorption was associated with coagulopathy (68.0% vs. 54.9%, p < 0.0001), cardiac arrhythmia (49.2% vs. 44.2%, p = 0.0272), and cardiopulmonary resuscitation (CPR, 19.3% vs. 13.1%, p = 0.0002). Further, haemoadsorption increased the chance of death for COVID-19 patients without septic shock (odds ratio, OR [within a 95% confidence interval, CI]; 1.40 [1.05-1.86]) and did not improve survival of septic shock patients (1.19 [0.85-1.67]). Independent variables with a significant impact on mortality included the use of extracorporeal membrane oxygenation (ECMO, 2.15 [1.68-2.76]) and CPR (1.60 [1.03-2.45]). The timing of the haemoadsorption therapy had no effect on patients´ outcomes. Due to inconclusive evidence for benefit and potential harm, haemoadsorption therapy should be limited to thoroughly designed clinical trials before introduced into clinical routine in the context of COVID-19.