The clinical, genomic, and microbiological profile of invasive multi-drug resistant Escherichia coli in a major teaching hospital in the United Kingdom

Abstract

AbstractEscherichia coliis a ubiquitous component of the human gut microbiome, but is also a common pathogen, causing around 40,000 bloodstream infections (BSI) in the UK annually. The number ofE. coliBSI has increased over the last decade in the UK, and emerging antimicrobial resistance (AMR) profiles threaten treatment options. Here, we combined clinical, epidemiological, and whole genome sequencing data with high content imaging to characterise over 300E. coliisolates associated with BSI in a large UK teaching hospital. Overall, only a limited number of sequence types (ST) were responsible for the majority of organisms causing invasive disease. The most abundant (20% of all isolates) was ST131, of which around 90% comprised the pandemic O25:H4 group. ST131-O25:H4 isolates were frequently multi-drug resistant (MDR), with a high prevalence of extended spectrum β-lactamases (ESBL) and fluoroquinolone resistance. There was no association between AMR phenotypes and the source ofE. colibacteraemia or whether the infection was healthcare-associated. Several clusters of ST131 were genetically similar, potentially suggesting a shared transmission network. However, there was no clear epidemiological associations between these cases, and they included organisms from both healthcare-associated and non-healthcare-associated origins. The majority of ST131 genetic clusters exhibited strong binding with an anti-O25b antibody, raising the possibility of developing rapid diagnostics targeting this pathogen. In summary, our data suggest that a restricted set of MDRE. colipopulations can be maintained and spread across both community and healthcare settings in this location, contributing disproportionately to invasive disease and AMR.Impact statementThe pandemic ST131-O25:H4 lineage was a common cause ofE. colibloodstream infections in this location, and carried multiple AMR mechanisms including ESBL and fluoroquinolone resistance. The conserved antigenicity of ST131-O25:H4 raises the possibility of developing targeted immune therapeutics and rapid diagnostics for this common and frequently multi-drug resistant pathogen.