Bacterial genotypic and patient risk factors for adverse outcomes in Escherichia coli bloodstream infections: a prospective molecular epidemiological study

Author:

Jauneikaite Elita12ORCID,Honeyford Kate13,Blandy Oliver1,Mosavie Mia1,Pearson Max1,Ramzan Farzan A.1,Ellington Matthew J.14ORCID,Parkhill Julian56,Costelloe Céire E.3,Woodford Neil14,Sriskandan Shiranee17ORCID

Affiliation:

1. NIHR Health Protection Research Unit for Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London , London, UK

2. Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London , London, UK

3. Global Digital Health Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London , London, UK

4. National Infection Service Laboratories, National Infection Service, UK Health Security Agency (formerly Public Health England) , UK

5. Wellcome Sanger Institute , Hinxton, Cambridge, UK

6. Department of Veterinary Medicine, University of Cambridge , Cambridge, UK

7. Medical Research Council Centre for Molecular Bacteriology & Infection, Imperial College London , London, UK

Abstract

Abstract Objectives Escherichia coli bloodstream infections have shown a sustained increase in England, for reasons that are unknown. Furthermore, the contribution of MDR lineages such as ST131 to overall E. coli disease burden and outcome is undetermined. Methods We genome-sequenced E. coli blood isolates from all patients with E. coli bacteraemia in north-west London from July 2015 to August 2016 and assigned MLST genotypes, virulence factors and AMR genes to all isolates. Isolate STs were then linked to phenotypic antimicrobial susceptibility, patient demographics and clinical outcome data to explore relationships between the E. coli STs, patient factors and outcomes. Results A total of 551 E. coli genomes were analysed. Four STs (ST131, 21.2%; ST73, 14.5%; ST69, 9.3%; and ST95, 8.2%) accounted for over half of cases. E. coli genotype ST131-C2 was associated with phenotypic non-susceptibility to quinolones, third-generation cephalosporins, amoxicillin, amoxicillin/clavulanic acid, gentamicin and trimethoprim. Among 300 patients from whom outcome was known, an association between the ST131-C2 lineage and longer length of stay was detected, although multivariable regression modelling did not demonstrate an association between E. coli ST and mortality. Several unexpected associations were identified between gentamicin non-susceptibility, ethnicity, sex and adverse outcomes, requiring further research. Conclusions Although E. coli ST was associated with defined antimicrobial non-susceptibility patterns and prolonged length of stay, E. coli ST was not associated with increased mortality. ST131 has outcompeted other lineages in north-west London. Where ST131 is prevalent, caution is required when devising empiric regimens for suspected Gram-negative sepsis, in particular the pairing of β-lactam agents with gentamicin.

Funder

National Institute for Health Research Health Protection Research Unit

NIHR HPRU

University of Cambridge

University of Warwick

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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