Activity of cefiderocol, ceftazidime-avibactam, and eravacycline against extended-spectrum cephalosporin-resistant Escherichia coli clinical isolates (2012–20017) in relation to phylogenetic background, sequence type 131 subclones, blaCTX-M genotype, and coresistance

Brian D. Johnston, Paul Thuras, Stephen B. Porter, Connie Clabots, James R. Johnsona

Research output: Contribution to journalArticlepeer-review

Abstract

Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (blaCTX-M-15-associated) H30Rx subclone and (blaCTX-M-27-associated) C1-M27 subset within the H30R1 subclone. We assessed cefiderocol, ceftazidime-avibactam, eravacycline, and 11 comparators for activity against 216 well-characterized ESCREC isolates (Minnesota, 2012–2017), then compared broth microdilution MICs with phylogenetic and clonal background, beta-lactamase genotype (blaCTX-M; group 1 and 9 variants), and coresistance. Percent susceptible was >95% (cefiderocol, ceftazidime-avibactam, eravacycline, carbapenems, amikacin, piperacillin-tazobactam, tigecycline), 64% to 75% (gentamicin, minocycline), or <40% (ceftazidime, levofloxacin, colistin). MICs varied significantly by multiple bacterial characteristics, in agent-specific patterns. The least-susceptible ST131 subset was the non-C1-M27 fraction within H30R1. Cefiderocol, ceftazidime-avibactam, and eravacycline MICs tended to be higher among isolates resistant (vs. susceptible) to diverse comparators. Thus, cefiderocol, ceftazidime-avibactam, and eravacycline are promising carbapenem-sparing alternatives for treating ESCREC infections, and their strength of activity varies in relation to diverse bacterial characteristics.

Original languageEnglish (US)
Article number115314
JournalDiagnostic Microbiology and Infectious Disease
Volume100
Issue number1
DOIs
StatePublished - May 2021

Bibliographical note

Funding Information:
This work was supported in part by research grants from Allergan, Shionogi & Co. Ltd., and Tetraphase Pharmaceuticals and by the Office of Research Development, Department of Veterans Affairs , grant # 2I01CX000920-04 (JRJ). The funders had no control over the content of the report or the decision to publish. The opinions expressed are those of the authors and not necessarily those of the authors’ institutions or the Department of Veterans Affairs.

Publisher Copyright:
© 2021

Keywords

  • antimicrobial therapy
  • bla genotype
  • cefiderocol
  • ceftazidime-avibactam
  • E. coli ST131 H30
  • eravacycline
  • extended-spectrum cephalosporin-resistant
  • minimum inhibitory concentration
  • multidrug resistance

PubMed: MeSH publication types

  • Journal Article

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