A microbiological and genomic perspective of globally collected Escherichia coli from adults hospitalized with invasive E. coli disease

Author:

Arconada Nuin Enya1ORCID,Vilken Tuba1,Xavier Basil Britto12ORCID,Doua Joachim3,Morrow Brian4,Geurtsen Jeroen5,Go Oscar4,Spiessens Bart3,Sarnecki Michal6,Poolman Jan5,Bonten Marc78,Ekkelenkamp Miquel9,Lammens Christine1,Goossens Herman1,Glupczynski Youri1,Van Puyvelde Sandra110ORCID, ,Leten Gert,Van Mieghem Sofie,Violette Madison,Munshi Sonal,Aitabi Moussa,Azzini Anna Maria,Righi Elda,Salerno Nicola Duccio,Cascio Giuliana Lo,Cremonini Eleonora,Pascual Álvaro,Espíndola Reinaldo,Palomo Virginia,Barraud Olivier,Walker Sarah V,Akai Naomi,Kimura Risa,Lakatos Louis,De Blacam Killian,Thaden Joshua,Ruffin Felicia,Dagher Michael

Affiliation:

1. Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp , Antwerp , Belgium

2. Department of Medical Microbiology and Infection Control, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands

3. Janssen Research & Development, Infectious Diseases & Vaccines, Janssen Pharmaceutica , Beerse , Belgium

4. Janssen Research & Development , Raritan, NJ , USA

5. Bacterial Vaccines Discovery & Early Development, Janssen Vaccines & Prevention B.V. , Leiden , The Netherlands

6. Janssen Vaccines, Branch of Cilag GmbH International , Bern , Switzerland

7. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University , Utrecht , The Netherlands

8. ECRAID , Utrecht , The Netherlands

9. Department of Medical Microbiology, University Medical Center Utrecht , Utrecht , The Netherlands

10. Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine , Cambridge Biomedical Campus, Cambridge CB2 0AW , UK

Abstract

Abstract Objectives Escherichia coli can cause infections in the urinary tract and in normally sterile body sites leading to invasive E. coli disease (IED), including bacteraemia and sepsis, with older populations at increased risk. We aimed to estimate the theoretical coverage rate by the ExPEC4V and 9V vaccine candidates. In addition, we aimed at better understanding the diversity of E. coli isolates, including their genetic and phenotypic antimicrobial resistance (AMR), sequence types (STs), O-serotypes and the bacterial population structure. Methods Blood and urine culture E. coli isolates (n = 304) were collected from hospitalized patients ≥60 years (n = 238) with IED during a multicentric, observational study across three continents. All isolates were tested for antimicrobial susceptibility, O-serotyped, whole-genome sequenced and bioinformatically analysed. Results A large diversity of STs and of O-serotypes were identified across all centres, with O25b-ST131, O6-ST73 and O1-ST95 being the most prevalent types. A total of 45.4% and 64.7% of all isolates were found to have an O-serotype covered by the ExPEC4V and ExPEC9V vaccine candidates, respectively. The overall frequency of MDR was 37.4% and ST131 was predominant among MDR isolates. Low in-patient genetic variability was observed in cases where multiple isolates were collected from the same patient. Conclusions Our results highlight the predominance of MDR O25b-ST131 E. coli isolates across diverse geographic areas. These findings provide further baseline data on the theoretical coverage of novel vaccines targeting E. coli associated with IED in older adults and their associated AMR levels.

Funder

University Medical Center Utrecht

European Federation of Pharmaceutical Industries and Associations

Innovative Medicines Initiative Joint Undertaking

European Union Seventh Framework Program

UMC Utrecht

Janssen Research & Development

Publisher

Oxford University Press (OUP)

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