Prognostic Factors of Escherichia Coli Bloodstream Infections in the Face of Emerging Multi-resistance, Severity Score and Therapeutic Implications

The determinants associated with severe outcome and death from Escherichia coli bloodstream infections (BSI) remain poorly understood. The epidemiology of E. coli BSI has recently changed dramatically with the global emergence of multiresistant strains producing extended-spectrum ß-lactamases (ESBL). Outcome is worse in case of ESBL-E. coli, which may be due to the intrinsic virulence of ESBL-E. coli or to a delayed adequate empirical antibiotic therapy because of multiresistance. Predicting the severity of an infection as soon as the initial clinical assessment is of major importance to provide the best care, while limiting unnecessary hospitalizations and costs. Yet, no simple clinical score exists to predict the severity of E. coli infections.

In a translational approach, the investigators will include during a maximum of one year 500 adults with E. coli BSI hospitalized in 7 hospitals in the Paris area, France. Precise clinical data will be collected at inclusion and 28 days after inclusion or upon patient's discharge (if before day 28). The primary endpoint of the study is death from E. coli BSI at day 28.

The first aim is to determine risk-factors for death at day 28, including clinical and bacteriological factors (determined by WGS) in the era of the global emergence of ESBL producing E. coli. The second aim is to determine virulence characteristics of ESBL strains both at the genome and phenotypic level thanks to a mouse model of septicaemia, and compare them to the clinical data. The third aim, will establish and evaluate a simple clinical severity score (named COLISCORE), in order to help clinician evaluate patients' severity upon initial clinical evaluation and particularly to detect patients at risk of severe outcome. The ultimate goal of this work is to have a clinical impact on patients' management, by understanding the determinants of patient severity due to E. coli BSI in the context of current major epidemiological changes.