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Defining nosocomial transmission of Escherichia coli and antimicrobial resistance genes: a genomic surveillance study

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Ludden, Catherine 
Gouliouris, Theo 
Coll, Francesc 


E. coli is a leading cause of bloodstream infections. Developing interventions to reduce this burden requires an understanding of the frequency of nosocomial transmission, but available evidence is limited. This study aimed to detect and characterise transmission of E. coli and associated plasmids in a hospitalised cohort. Methods: Genomic surveillance of E. coli was conducted in a prospective observational cohort study of hospitalised adult patients over 6 months in Cambridge, England. Stool samples were collected from study participants on admission, weekly and discharge. We sequenced multiple E. coli colonies (median=5) from each stool. A genetic threshold to infer E. coli transmission was defined by maximum within-host SNP diversity and the probability of drawing observed pairs of between-patient isolates at different SNP thresholds. Findings: We obtained and cultured 376 stools from 149 patients, of which 152 stools from 97 patients grew E. coli. We identified extensive diversity in the bacterial population (90 sequence types, STs), and mixed E. coli ST carriage in almost half of patients (26%, 13% and 6% patients carried 2, 3 or >4 STs, respectively). Using a 17 SNP cut-off we identified 10 clusters (defined as >2 cases) involving 20 patients. The largest cluster contained 7 patients, while 4 patients were linked to multiple clusters. Half of cases in the 10 clusters also had a strong epidemiological link to another patient in the cluster. A minority of all patients (17/149, 11%) carried extended-spectrum beta-lactamase (ESBL)-producing E.coli, the most common of which was blaCTX-M-15 (12/17, 71%). Long-read sequencing revealed that blaCTX-M- 40 was often integrated into the chromosome, with little evidence for plasmid-mediated transmission. Seven patients developed E. coli bloodstream infection, four with identical strains in those in stool; two of these had documented nosocomial acquisition. Interpretation: We provide evidence of bacterial transmission and endogenous infections during routine care by integrating genomic and epidemiological data and through determination of a genetic similarity cut-off informed by within-host diversity in the population studied. Our findings challenge single colony-based investigations, and the paradigm of plasmid spread in this setting.



Adult, Anti-Bacterial Agents, Cross Infection, Drug Resistance, Bacterial, Escherichia coli, Escherichia coli Infections, Genomics, Humans, Prospective Studies, beta-Lactamases

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The Lancet Microbe

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Wellcome Trust (098600/Z/12/Z)
Wellcome Trust (103387/Z/13/Z)
National Institute for Health and Care Research (HICF-T5-342)