Impact of virulence genes on sepsis severity and survival in Escherichia coli bacteremia

Abstract

Extraintestinal pathogenic Escherichia coli (ExPEC) are a frequent cause of bacteremia and sepsis, but the role of ExPEC genetic virulence factors (VFs) in sepsis development and outcome is ill-defined. Prospective study including 120 adult patients with E. coli bacteremia to investigate the impact of bacterial and host factors on sepsis severity and mortality. Patients' clinical and demographic data were registered. Phylogenetic background of E. coli isolates was analyzed by SNP pyrosequencing and VFs by PCR. The E. coli isolates presented an epidemic population structure with 6 dominant clones making up to half of the isolates. VF gene profiles were highly diverse. Multivariate analysis for sepsis severity showed that the presence of cnf and blaTEM genes increased the risk of severe illness by 6.75 (95% confidence interval [CI] 1.79-24.71) and 2.59 (95% CI 1.04-6.43) times respectively, while each point in the Pitt score increased the risk by 1.34 (95% CI 1.02-1.76) times. Multivariate analysis for mortality showed that active chemotherapy (OR 17.87, 95% CI 3.35-95.45), McCabe-Jackson Index (OR for rapidly fatal category 120.15, 95% CI 4.19-3446.23), Pitt index (OR 1.78, 95% CI 1.25-2.56) and presence of fyuA gene (OR 8.05, 95% CI 1.37-47.12) were associated to increased mortality while the presence of P fimbriae genes had a protective role (OR 0.094, 95%IC 0.018-0.494). Bacteremic E. coli had a high diversity of genetic backgrounds and VF gene profiles. Bacterial VFs and host determinants had an impact on disease evolution and mortality.

Bloodstream Infection with Extended-spectrum Beta-lactamase–producingEscherichia coli: the role of virulence genes

“…[18] Mora-Rillo et al found positivity for fyuA associated with increased mortality, and that of P fimbriae genes had a protective role. [19] A study in Spain of ESBL E coli bacteremia showed ibeA associated with increased mortality, with papG alleleII having a protective effect. [6]…”

The importance of the “V”-Factor:Escherichia colibacteremia and sepsis

“…Numerous studies throughout the late nineties and into this decade have sought to tease out solutions to this question so that clinicians may overcome the health burden such bacteremia exemplifies. While some studies have demonstrated that host risk factors are more detrimental to outcomes in sepsis severity, and MoraRillo's work presented here posits that virulence factors (VF) have a significant impact on survival outcomes 1 , it is likely to be more complex than either one of these hypotheses alone. Larger multi center studies are needed in order to address these complex interactions.…”

“…This is in contrast to MoraRillo's work that showed a strong correlation between presence of cnf and sepsis severity. 1 Hly genes were found in a higher proportion of isolates causing pyelonephritis than cystitis and finally that traT was shown to be the most prevalent virulence determinant. This study highlights the diversity of bacterial VF expression in various host contexts and indicates that understanding these is a useful tool for patient management.…”

“…In the previous issue of Virulence, Mora-Rillo et al 1 publish a report investigating the role of virulence factors (VFs) on sepsis severity and survival outcomes in patients with extra-intestinal pathogenic E. coli infections (ExPEC). Mortality caused by E. coli bacteremia and sepsis remains high and is now one the top 10 causes of death in the western world.…”

“…1 In this study MoraRillo et al delineated strains from each common phylogroup (B2, A, D, B1) and 50 SAPs of which, 37 were unique and only 6 appeared in more than 5 isolates, but accounted for 50.8% of all the isolates. 1 The majority of human E. coli strains exist as commensal bacteria of the intestinal tract 4 of particular interest in the context of sepsis causing infections, however, are outgrowth or infection of populations of 2 additional categories, intestinal pathogenic, entero-pathogenic (of which there are 6 classifications, EPEC (enteropathogenic), EHEC (enterohaemorrhagic), ETEC (enterotoxigenic), EAEC (enteroaggregative), EIEC (enteroinvasive) and DAEC (diffusely adherent)) and ExPEC, which are responsible for urinary tract infections (UTI) and neonatal meningitis among other conditions. 4 Inter-species transmission of E. coli strains is common and numerous studies have shown the high degree of similarity between human, avian and porcine virulence mechanisms and bacterial populations.…”