Piperacillin/tazobactam-resistant, cephalosporin-susceptible Escherichia coli bloodstream infections are driven by multiple acquisition of resistance across diverse sequence types
Authors
Edwards, THeinz, E
van Aartsen, J
Howard, A
Roberts, Paul
Corless, C
Fraser, AJ
Williams, CT
Bulgasim, I
Cuevas, LE
Parry, CM
Roberts, AP
Adams, ER
Mason, J
Hubbard, ATM
Issue Date
2022-04-11
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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 predic-tion of the TZP-R/3GC-S phenotype from genomic data.Citation
Edwards, T., Heinz, E., van Aartsen, J. et al. (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). https://doi.org/10.1099/mgen.0.000789Publisher
Microbiology SocietyJournal
Microbial GenomicsPubMed ID
35404783 (pubmed)Type
Journal articleLanguage
enDescription
© 2022 The Authors. Published by the Microbiology Society. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1099/mgen.0.000789ISSN
2057-5858EISSN
2057-5858Sponsors
This work was supported by the LSTM Director’s Catalyst Fund, separately awarded to T.E. and A.T.M.H. E.H. acknowledges support from a Wellcome SEED Award (217303/Z/19/Z). A.P.R. would like to acknowledge funding from the AMR Cross-Council Initiative through a grant from the Medical Research Council, a Council of UK Research and Innovation (Grant Number; MR/S004793/1), and the National Institute for Health Research (Grant number; NIHR200632).ae974a485f413a2113503eed53cd6c53
10.1099/mgen.0.000789
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