Whole-genome Characterisation of Escherichia Coli Isolates from Patients with Bacteraemia Presenting with Sepsis or Septic Shock in Spain: a Multicentre Cross-Sectional Study

Background Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions. Methods E coli blood isolates from a multicentre cross-sectional study of patients older than 14 years presenting with sepsis or septic shock (according to the Third International Consensus De fi nitions for Sepsis and Septic Shock criteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identi fi ed. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A, B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence -associated genes, pathogenicity islands, AMR, and AMR -associated genes. Frequencies were compared using chi(2) or Fisher ' s exact tests, and continuous variables using the Mann -Whitney test, with Bonferroni correction for multiple comparisons. Findings We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3.85 STs were identi fi ed, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No signi fi cant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0 . 0045). Median virulence score was higher in group 1 (median 25 . 0 [IQR 20 . 5 - 29 . 0) than in group 2 (median 14 . 5 [9 . 0 - 20 . 0]; p < 0 . 0001) and group 3 (median 21 [16 . 5 - 23 . 0]; p < 0 . 0001); prevalence of several pathogenicity islands was higher in group 1. No signi fi cant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29 - 35]) than the other predominant clones (median range 21 - 28). Some virulence genes and pathogenicity islands were signi fi cantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably bla(CTX-M-,15) and bla(OXA)-, . Interpretation In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection.