Daily Sepsis Research Analysis
Analyzed 25 papers and selected 3 impactful papers.
Summary
Three studies shift the sepsis conversation from pathogens to practice: bacterial genomics (E. coli ST69 and pic) link organism traits to sepsis severity, a West African cohort documents a dramatic rise in multidrug-resistant Gram-negative infections with higher mortality, and a prospective implementation of rapid AST shortens reporting time and halves mortality in Gram-negative bacteremia.
Research Themes
- Pathogen genomics and sepsis severity
- Rapid diagnostics and antimicrobial stewardship
- Antimicrobial resistance trends in pediatric invasive infections
Selected Articles
1. A matched case-control study on Escherichia coli factors contributing to sepsis and septic shock in bacteraemic patients.
In matched E. coli bacteremia cases, the ST69 clone and the pic gene were independently associated with sepsis/septic shock, whereas papC and fdeC showed protective associations. A conditional logistic model incorporating these factors achieved AUROC 0.81, highlighting pathogen genomics as a determinant of sepsis severity.
Impact: This study links specific bacterial genetic determinants to sepsis severity in humans, offering targets for diagnostics and potential interventions beyond host-centric models.
Clinical Implications: Rapid assays for ST69 and pic could support early risk stratification in E. coli bacteremia and inform aggressive monitoring or therapy. Findings motivate pathogen-informed sepsis management.
Key Findings
- ST69 clone independently associated with sepsis/septic shock (adjusted OR 7.53; 95% CI 1.06-35.05).
- pic gene presence associated with higher odds of sepsis/shock (adjusted OR 4.38; 95% CI 1.53-12.54).
- papC (adjusted OR 0.30) and fdeC (adjusted OR 0.18) showed protective associations.
- Predictive model achieved AUROC 0.81 (95% CI 0.74-0.87).
Methodological Strengths
- Matched case-control design controlling for multiple clinical confounders (age, comorbidity, source, acquisition, empiric therapy).
- Whole-genome sequencing with comprehensive virulence/resistance profiling and conditional logistic regression.
Limitations
- Observational design cannot exclude residual confounding.
- Generalizability may be limited to similar healthcare settings; external validation is needed.
Future Directions: Validate genomic predictors in multicenter cohorts, develop rapid clinical assays for ST69/pic, and perform mechanistic studies to assess pic as a therapeutic or vaccine target.
BACKGROUND: One third of patients with Escherichia coli bacteraemia develop a dysregulated inflammatory response (sepsis/septic shock). Our objective was to investigate whether specific microbiological determinants of E. coli are associated to presentation with sepsis/shock. METHODS: A matched case-control study was performed; 101 case-patients with E. coli bacteraemia presenting with sepsis (SEPSIS-3 criteria) and 101 control-patients with E. coli bacteraemia without sepsis were matched by service, sex, age, Charlson index, acquisition and source of the bacteraemia and empirical treatment. Whole genome sequencing of E. coli isolates was performed (Illumina MiSeq Inc.). Sequence type, serotype, fimH type, virulence factors, antibiotic resistance genes, plasmid replicons pathogenicity islands and prophages were determined. A multivariate model was built for presentation with sepsis/septic shock using conditional logistic regression. The predictive capacity on the observed data was measured with the area under the ROC curve (AUROC) with 95% confidence intervals (CI). RESULTS: Here we show that in the multivariate model (adjusted OR; 95% CI), the ST69 clone (7.53; 1.06-35.05) and pic gene (4.38; 1.53-12.54) are associated to presentation with sepsis/shock, while the genes papC (0.30; 0.12-0.74) and fdeC (0.18; 0.03-1.32) show a protective effect. The AUROC of this model is 0.81 (95% CI 0.74-0.87). CONCLUSIONS: We identify E. coli bacterial factors associated with severe clinical presentation in patients with bacteraemia. Further studies would be needed to consider these factors as potential preventive or therapeutic targets. Escherichia coli is the most common cause of invasive infections, including bacteraemia that often progresses to severe conditions like sepsis or septic shock. While many host factors determine the severity of illness, this study looked at the bacterial factors that may contribute to sepsis severity. We directly compared E. coli-infected patients with similar traits but either with or without sepsis to control for patient factors Our analysis revealed that the ST69 clone and the presence of the pic gene were significantly associated with an increased risk of sepsis/septic shock, whereas the adhesion genes papC and fdeC were associated with a lower risk. These key findings underscore a role for specific E. coli genetic factors in determining clinical severity, thereby providing potential bacterial targets for the development of improved diagnostics and novel preventive or therapeutic interventions.
2. Longitudinal Trends in Pediatric Non-Salmonella Gram-negative Enterobacterales Infections at a Tertiary Care Center in West Africa, 2005-2023.
Over 19 years in Mali, the burden of non-Salmonella Gram-negative Enterobacterales among pediatric invasive infections rose from 6% to 38%, with third-generation cephalosporin and multidrug resistance escalating to 93% by 2021–2023. These infections were associated with higher in-hospital mortality, and WGS identified Pantoea dispersa and multiple resistance genes.
Impact: Large-scale longitudinal data from West Africa quantify the rapid rise of MDR Gram-negative infections and link them to increased mortality, informing empiric therapy and stewardship in resource-limited settings.
Clinical Implications: Empiric regimens may require revision to cover ESBL/AmpC/CRE in high-burden settings; investment in rapid diagnostics, microbiology capacity, and antimicrobial access and stewardship is essential.
Key Findings
- Proportion of non-Salmonella GNE among pathogen-positive cases increased from 6% (2005) to 38% (2023).
- Third-generation cephalosporin resistance and multidrug resistance rose to 93% by 2021–2023.
- Non-Salmonella GNE associated with higher in-hospital mortality across age strata (e.g., OR 3.17 in 0–2 months).
- WGS identified the emerging pathogen Pantoea dispersa and multiple resistance genes in 2021–2023 isolates.
Methodological Strengths
- Large, 19-year retrospective cohort (n=3,803) with mortality outcomes.
- Integration of whole-genome sequencing to characterize resistance determinants in recent isolates.
Limitations
- Single-center referral setting may limit generalizability.
- Temporal changes in clinical practice or laboratory methods could influence trends; WGS applied to a subset only.
Future Directions: Multicenter surveillance with harmonized methods, interventional stewardship trials, and access strategies for effective antibiotics in similar settings.
BACKGROUND: Despite data demonstrating the high prevalence of third-generation cephalosporin resistant gram-negative Enterobacterales (GNE) among children in sub-Saharan Africa, longitudinal descriptions of resistance among these pathogens from Francophone West Africa remain rare. METHODS: We conducted a retrospective analysis of pathogen-positive children 0-15 years old included in an invasive bacterial infection study at l'Hôpital Gabriel Touré (in Bamako, Mali) from 2005-2023. We aimed to describe changes in pathogen burden and non-Salmonella GNE resistance over time and compare in-hospital mortality between patients with and without non-Salmonella GNE pathogens. Isolates from 2021-2023 underwent whole genome sequencing to identify genes conferring antimicrobial resistance. RESULTS: Of 3,803 pathogen-positive patients, 392 grew at least one non-Salmonella GNE pathogen. The proportion of pathogen-positive patients with non-Salmonella GNE increased (6% vs. 38%) from 2005-2023. Third-generation cephalosporin and multidrug resistance among non-Salmonella GNE increased from 30% and 55%, respectively, in 2005-2009, to 93% (both) by 2021-2023. Children 0-2 months old from outside Bamako and 3 months-15 years old from and from outside Bamako with non-Salmonella GNE had higher mortality odds (3.17, 95% CI 1.69-5.95; 2.13, 95% CI 1.44-3.14; and 2.25, 95% CI 1.38-3.66, respectively) than similar patients with other pathogens. Sequencing confirmed the presence of the emerging pathogen Pantoea dispersa and revealed genes conferring multidrug resistance. CONCLUSIONS: Data from this large pediatric referral center in Mali show a high and rising burden of multidrug-resistant gram-negative Enterobacterales. These patterns reflect concerns increasingly reported across sub-Saharan Africa, highlighting the urgency of strengthening antimicrobial access, diagnostics, and stewardship strategies in similar settings.
3. Clinical impact of rapid antimicrobial susceptibility testing in patients with bacteremia due to gram-negative bacilli.
In a prospective two-arm comparison of 120 patients with Gram-negative bacteremia, rapid AST (Vitek Reveal) reduced turnaround time from 40 to 12 hours and was associated with markedly lower mortality (13.3% vs 38.3%). Length of stay trended lower but was not statistically significant.
Impact: Demonstrates clinically meaningful mortality reduction associated with rapid AST implementation, emphasizing the value of diagnostic speed in sepsis management.
Clinical Implications: Hospitals should consider implementing rapid AST platforms integrated with stewardship to accelerate targeted therapy and potentially reduce mortality in Gram-negative sepsis.
Key Findings
- Rapid AST (Vitek Reveal) reduced mortality vs conventional AST (13.3% vs 38.3%; p=0.002).
- Turnaround time to AST results decreased from 40 to 12 hours (p<0.001).
- Length of stay was shorter in the rapid AST group (18 vs 24.5 days; p=0.128), though not statistically significant.
Methodological Strengths
- Prospective comparative design with clinically meaningful endpoints (mortality, turnaround time).
- Direct head-to-head evaluation of laboratory platforms linked to real-world outcomes.
Limitations
- Nonrandomized design with potential confounding and selection bias.
- Single-center study with modest sample size limits generalizability.
Future Directions: Conduct multicenter randomized or quasi-experimental implementations with cost-effectiveness analysis and pathogen-specific subgroup assessments.
INTRODUCTION: Bacteremia and sepsis cause high morbidity and mortality worldwide. Rapid identification of bacteria and timely antimicrobial susceptibility testing (AST) can be crucial for patient survival. In the present study, we have compared isolates from patients whose ASTs were processed using MicroScan Walkaway Plus with those patients whose ASTs were processed more quickly using Vitek® Reveal™. We analyzed mortality, turnaround time to targeted therapy, and length of stay between the two groups, as well as other parameters. MATERIAL AND METHODS: In this prospective study, 120 patients with bacteremia caused by Gram-negative bacilli were included. In 60 patients, conventional AST (MicroScan WalkAway Plus) was performed, whereas in the other 60 patients, rapid AST (Vitek® Reveal™) was carried out. RESULTS: The mortality rates were 13.3% and 38.3% for patients whose ASTs were performed with Vitek® Reveal™ and MicroScan WalkAway Plus, respectively (p=0.002). The average length of stay was 18 days per patient in the Vitek® Reveal™ group and 24.5 days for the MicroScan group (p=0.128). The average turnaround time was 12 hours per patient for Vitek® Reveal™ and 40 hours for MicroScan (p<0.001). CONCLUSIONS: The introduction of rapid AST techniques such as Vitek® Reveal™ has allowed a shorter turnaround time for reports on AST than when using normal AST techniques. This allows most AST results to be available earlier in the Laboratory Information System, allowing physicians to initiate more quickly in establishing correct treatment. Finally, these actions have resulted in reduced mortality due to faster clinical decision-making in these critically ill patients. INTRODUCCIÓN: La bacteriemia y la sepsis causan una elevada morbilidad y mortalidad en todo el mundo. La identificación rápida de las bacterias y la realización oportuna de las pruebas de sensibilidad antimicrobiana (AST) pueden ser cruciales para la supervivencia del paciente. En el presente estudio, comparamos aislamientos de pacientes cuyos AST se procesaron mediante MicroScan WalkAway Plus con los de pacientes cuyos AST se procesaron de forma más rápida utilizando Vitek® Reveal™. Analizamos la mortalidad, el tiempo hasta la instauración de la terapia dirigida y la duración de la estancia hospitalaria entre ambos grupos, así como otros parámetros. MATERIAL Y MÉTODOS: En este estudio prospectivo se incluyeron 120 pacientes con bacteriemia causada por bacilos gramnegativos. En 60 pacientes se realizó un AST convencional (MicroScan WalkAway Plus), mientras que en los otros 60 se llevó a cabo un AST rápido (Vitek® Reveal™). RESULTADOS: Las tasas de mortalidad fueron del 13,3% y del 38,3% en los pacientes cuyos AST se realizaron con Vitek® Reveal™ y MicroScan WalkAway Plus, respectivamente (p=0,002). La duración media de la estancia hospitalaria fue de 18 días por paciente en el grupo Vitek® Reveal™ y de 24,5 días en el grupo MicroScan (p=0,128). El tiempo medio de respuesta fue de 12 horas por paciente para Vitek® Reveal™ y de 40 horas para MicroScan (p<0,001). CONCLUSIONES: La introducción de técnicas rápidas de AST, como Vitek® Reveal™, ha permitido reducir el tiempo de respuesta de los informes de sensibilidad antimicrobiana en comparación con las técnicas convencionales. Esto posibilita que la mayoría de los resultados de AST estén disponibles de forma más temprana en el sistema de información del laboratorio, permitiendo a los médicos iniciar antes el tratamiento adecuado. Finalmente, estas mejoras se han traducido en una reducción de la mortalidad gracias a una toma de decisiones clínicas más rápida en estos pacientes críticamente enfermos.