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

• Published in: The Lancet. Microbe 2021-09, Vol.2 (9), p.e472-e480
• Main Authors: Ludden, Catherine, Coll, Francesc, Gouliouris, Theodore, Restif, Olivier, Blane, Beth, Blackwell, Grace A, Kumar, Narender, Naydenova, Plamena, Crawley, Charles, Brown, Nicholas M, Parkhill, Julian, Peacock, Sharon J
• Format: Article
• Language: English
• Subjects: Adult; Anti-Bacterial Agents - pharmacology; beta-Lactamases - genetics; Cross Infection - epidemiology; Drug Resistance, Bacterial; Escherichia coli - genetics; Escherichia coli Infections - epidemiology; Genomics; Humans; Prospective Studies
• ISSN: 2666-5247; 2666-5247
• DOI: 10.1016/S2666-5247(21)00117-8

Escherichia coli is a leading cause of bloodstream infections. Developing interventions to reduce E coli infections requires an understanding of the frequency of nosocomial transmission, but the available evidence is scarce. We aimed to detect and characterise transmission of E coli and associated plasmids in a hospital setting. In this prospective observational cohort study, patients were admitted to two adult haematology wards at the Cambridge University Hospitals NHS Foundation Trust in England. Patients aged 16 years and older who were treated for haematological malignancies were included. Stool samples were collected from study participants on admission, once per week, and at discharge. We sequenced multiple E coli isolates (both extended spectrum β-lactamase [ESBL]-producing and non-ESBL-producing) from each stool sample. A genetic threshold to infer E coli transmission was defined by maximum within-host single nucleotide polymorphism (SNP) diversity and the probability of drawing observed pairs of between-patient isolates at different SNP thresholds. Putative transmission clusters were identified when sequences were less than the genetic threshold. Epidemiological links for each transmission event were investigated. We sequenced all E coli positive blood samples from the two adult haematology wards. We recruited 174 (51%) of 338 adult patients admitted to the wards between May 13 and Nov 13, 2015. We obtained and cultured 376 stool samples from 149 patients, of which 152 samples from 97 (65%) patients grew E coli. Whole-genome sequencing was done on 970 isolates. We identified extensive diversity in the bacterial population (90 sequence types) and mixed E coli sequence type carriage. 24 (26%) patients carried two sequence types, 12 (13%) carried three, and six (6%) patients carried four or more sequence types. Using a 17 SNP cutoff we identified ten clusters in 20 patients. The largest cluster contained seven patients, whereas four patients were included in multiple clusters. Strong epidemiological links were found between patients in seven clusters. 17 (11%) of 149 patients had stool samples positive for ESBL-producing E coli, the most common of which was associated with blaCTX-M-15 (12 [71%] of 17). Long-read sequencing revealed that blaCTX-M-15 was often integrated into the chromosome, with little evidence for plasmid transmission. Seven patients developed E coli bloodstream infection, four with identical strains to those in their stool; two of t