A matched case-control study on Escherichia coli factors contributing to sepsis and septic shock in bacteraemic patients

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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. 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). 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). 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. Maldonado, Lopez-Hernandez, et al. use a matched case-control study to compare E. coli-infected patients with or without sepsis. Their analysis shows that the ST69 clone is associated with risk of sepsis development, and certain genetic factors such as adhesion genes papC and fdeC were associated with a protective effect.

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