A matched case-control study on Escherichia coli factors contributing to sepsis and septic shock in bacteraemic patients
Description
One third of patients with Escherichia coli bacteraemia develop a dysregulated inflammatory response (sepsis/septic shock). In order to investigate whether specific microbiological determinants of E. coli are associated to presentation with sepsis/shock a matched case-control study was performed and 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. Quality analysis of genome assemblies, genome annotation and pan-genome analysis were performed in QUAST v5.2.0, Bakta v1.6.1 and Roary v3.13.0, respectively. Phylogenomic tree reconstruction based on the best-scoring maximum-likelihood (ML) inference tree for a DNA alignment was performed in RAxML v8.2.12 and best-scoring ML inference tree with branch lengths corrected to account for recombination events in ClonalFrameML v1.12. Other bioinformatics analyses including Principal Coordinate Analysis (PCoA), clustering based on PCoA, Boruta algorithm and Random Forest Models were performed in R v4.3.1 using the following core packages: tidyverse (2.0.0), caret (6.0-94), Boruta (8.0.0), ranger (0.17.0), vegan (2.6-4), and pROC (1.18.5).