Ten Years of Population-Level Genomic Escherichia coli and Klebsiella pneumoniae Serotype Surveillance Informs Vaccine Development for Invasive Infections.
Anti-Bacterial Agents
/ pharmacology
Drug Resistance, Multiple, Bacterial
/ genetics
Escherichia coli
Escherichia coli Infections
/ epidemiology
Genomics
Humans
Klebsiella Infections
/ epidemiology
Klebsiella pneumoniae
Microbial Sensitivity Tests
Serogroup
Vaccine Development
beta-Lactamases
/ genetics
Enterobacteriaceae
antimicrobial resistance
bloodstream infection
vaccine
whole genome sequencing
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
16 12 2021
16 12 2021
Historique:
received:
21
08
2020
pubmed:
8
1
2021
medline:
15
3
2022
entrez:
7
1
2021
Statut:
ppublish
Résumé
The incidence of bloodstream infections (BSIs) caused by Escherichia coli and Klebsiella pneumoniae is increasing, with substantial associated morbidity, mortality, and antimicrobial resistance. Unbiased serotyping studies to guide vaccine target selection are limited. We conducted unselected, population-level genomic surveillance of bloodstream E. coli and Klebsiella pneumoniae isolates from 2008 to 2018 in Oxfordshire, United Kingdom. We supplemented this with an analysis of publicly available global sequencing data (n = 3678). We sequenced 3478 E. coli isolates (3278 passed quality control) and 556 K. pneumoniae isolates (535 [K-antigen] and 549 [O-antigen] passed quality control). The 4 most common E. coli O-antigens (O1/O2/O6/O25) were identified in 1499/3278 isolates; the incidence of these O-types increased over time (incidence rate ratio per year [IRRy] = 1.14, 95% confidence interval [CI]: 1.11-1.16). These O-types accounted for 616/1434 multidrug-resistant (MDR) and 173/256 extended-spectrum beta-lactamase (ESBL)-resistant isolates in Oxfordshire but only 19/90 carbapenem-resistant isolates across all studies. For Klebsiella pneumoniae, the most common O-antigens (O2v2/O1v1/O3b/O1v2) accounted for 410/549 isolates; the incidence of BSIs caused by these also increased annually (IRRy = 1.09; 95% CI: 1.05-1.12). These O-types accounted for 122/148 MDR and 106/123 ESBL isolates in Oxfordshire and 557/734 carbapenem-resistant isolates across all studies. Conversely we observed substantial capsular antigen diversity. Analysis of 3678 isolates from global studies demonstrated the generalizability of these findings. For E. coli, based on serotyping, the ExPEC4V and ExPEC10V vaccines under investigation would cover 46% and 72% of Oxfordshire isolates respectively, and 47% and 71% of MDR isolates. O-antigen targeted vaccines may be useful in reducing the morbidity, mortality, and antimicrobial resistance associated with E. coli and K. pneumoniae BSIs.
Sections du résumé
BACKGROUND
The incidence of bloodstream infections (BSIs) caused by Escherichia coli and Klebsiella pneumoniae is increasing, with substantial associated morbidity, mortality, and antimicrobial resistance. Unbiased serotyping studies to guide vaccine target selection are limited.
METHODS
We conducted unselected, population-level genomic surveillance of bloodstream E. coli and Klebsiella pneumoniae isolates from 2008 to 2018 in Oxfordshire, United Kingdom. We supplemented this with an analysis of publicly available global sequencing data (n = 3678).
RESULTS
We sequenced 3478 E. coli isolates (3278 passed quality control) and 556 K. pneumoniae isolates (535 [K-antigen] and 549 [O-antigen] passed quality control). The 4 most common E. coli O-antigens (O1/O2/O6/O25) were identified in 1499/3278 isolates; the incidence of these O-types increased over time (incidence rate ratio per year [IRRy] = 1.14, 95% confidence interval [CI]: 1.11-1.16). These O-types accounted for 616/1434 multidrug-resistant (MDR) and 173/256 extended-spectrum beta-lactamase (ESBL)-resistant isolates in Oxfordshire but only 19/90 carbapenem-resistant isolates across all studies. For Klebsiella pneumoniae, the most common O-antigens (O2v2/O1v1/O3b/O1v2) accounted for 410/549 isolates; the incidence of BSIs caused by these also increased annually (IRRy = 1.09; 95% CI: 1.05-1.12). These O-types accounted for 122/148 MDR and 106/123 ESBL isolates in Oxfordshire and 557/734 carbapenem-resistant isolates across all studies. Conversely we observed substantial capsular antigen diversity. Analysis of 3678 isolates from global studies demonstrated the generalizability of these findings. For E. coli, based on serotyping, the ExPEC4V and ExPEC10V vaccines under investigation would cover 46% and 72% of Oxfordshire isolates respectively, and 47% and 71% of MDR isolates.
CONCLUSIONS
O-antigen targeted vaccines may be useful in reducing the morbidity, mortality, and antimicrobial resistance associated with E. coli and K. pneumoniae BSIs.
Identifiants
pubmed: 33411882
pii: 6067638
doi: 10.1093/cid/ciab006
pmc: PMC8677521
doi:
Substances chimiques
Anti-Bacterial Agents
0
beta-Lactamases
EC 3.5.2.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2276-2282Subventions
Organisme : National Institute for Health Research
ID : NIHR200915
Organisme : Medical Research Council
ID : MR/T001151/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203141/Z/16/Z
Pays : United Kingdom
Organisme : MRF
ID : MRF_MRF-145-0004-TPG-AVISO
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
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