Piperacillin/tazobactam resistant, cephalosporin susceptible Escherichia coli bloodstream infections are driven by multiple acquisition of resistance across diverse sequence types

Edwards, T., Heinz, E., van Aartsen, J., Howard, A., Roberts, P., Corless, C., Fraser, A.J., Williams, C.T., Bulgasim, I., Cuevas, L.E., Parry, C.M., Roberts, A.P., Adams, E.R., Mason, J. and Hubbard, A. ORCID: 0000-0001-6668-9179, 2022. Piperacillin/tazobactam resistant, cephalosporin susceptible Escherichia coli bloodstream infections are driven by multiple acquisition of resistance across diverse sequence types. Microbial Genomics, 8 (4): 000789. ISSN 2057-5858

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Abstract

Resistance to piperacillin/tazobactam (TZP) in Escherichia coli has predominantly been associated with mechanisms that confer resistance to third generation cephalosporins. Recent reports have identified E. coli strains with phenotypic resistance to piperacillin/tazobactam but susceptibility to third generation cephalosporins (TZP-R/3GC-S). In this study we sought to determine the genetic diversity of this phenotype in E. coli (n = 58) isolated between 2014-2017 at a single tertiary hospital in Liverpool, UK, as well as the associated resistance mechanisms. We compare our findings to a UK-wide collection of invasive E. coli isolates (n = 1509) with publicly available phenotypic and genotypic data. These data sets included the TZP-R/3GC-S phenotype (n = 68), and piperacillin/tazobactam and third generation cephalosporin-susceptible (TZP-S/3GC-S, n = 1271) phenotypes. The TZP-R/3GC-S phenotype was displayed in a broad range of sequence types which was mirrored in the same phenotype from the UK-wide collection, and the overall diversity of invasive E. coli isolates. The TZP-R/3GC-S isolates contained a diverse range of plasmids, indicating multiple acquisition events of TZP resistance mechanisms rather than clonal expansion of a particular plasmid or sequence type. The putative resistance mechanisms were equally diverse, including hyperproduction of TEM-1, either via strong promoters or gene amplification, carriage of inhibitor resistant β-lactamases, and an S133G blaCTX-M-15 mutation detected for the first time in clinical isolates. Several of these mechanisms were present at a lower abundance in the TZP-S/3GC-S isolates from the UK-wide collection, but without the associated phenotypic resistance to TZP. Eleven (19%) of the isolates had no putative mechanism identified from the genomic data. Our findings highlight the complexity of this cryptic phenotype and the need for continued phenotypic monitoring, as well as further investigation to improve detection and prediction of the TZP-R/3GC-S phenotype from genomic data.

Item Type: Journal article
Publication Title: Microbial Genomics
Creators: Edwards, T., Heinz, E., van Aartsen, J., Howard, A., Roberts, P., Corless, C., Fraser, A.J., Williams, C.T., Bulgasim, I., Cuevas, L.E., Parry, C.M., Roberts, A.P., Adams, E.R., Mason, J. and Hubbard, A.
Publisher: Microbiology Society
Date: 11 April 2022
Volume: 8
Number: 4
ISSN: 2057-5858
Identifiers:
NumberType
10.1099/mgen.0.000789DOI
1522224Other
Rights: © 2022 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Divisions: Schools > School of Science and Technology
Record created by: Laura Ward
Date Added: 01 Mar 2022 16:02
Last Modified: 21 Apr 2022 09:48
URI: http://irep.ntu.ac.uk/id/eprint/45778

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