Activity of cefiderocol, ceftazidime-avibactam, and eravacycline against carbapenem-resistant escherichia coli isolates from the united states and international sites in relation to clonal background, resistance genes, coresistance, and region

Brian D. Johnston, Paul Thuras, Stephen B. Porter, Melissa Anacker, Brittany VonBank, Paula Snippes Vagnone, Medora Witwer, Mariana Castanheira, James R. Johnson

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1 Scopus citations

Abstract

Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), the leading cause of extraintestinal E. coli infections globally, threatens therapeutic efficacy. Accordingly, we determined broth microdilution MICs for three distinctive newer agents, i.e., cefiderocol (CFDC), ceftazidime-avibactam (CZA), and eravacycline (ERV), plus 11 comparators, against 343 carbapenem-resistant (CR) clinical E. coli isolates, then compared susceptibility results with bacterial characteristics and region. The collection comprised 203 U.S. isolates (2002 to 2017) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003 to 2017). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant beta-lactamaseencoding genes. CFDC, CZA, and ERV exhibited the highest percent susceptible (82% to 98%) after tigecycline (TGC) (99%); avibactam improved CZA’s activity over that of CAZ (11% susceptible). Percent susceptible varied by phylogroup and ST for CFDC and CZA (greatest in phylogroups B2, D, and F, and in ST131, ST405, and ST648). Susceptibility also varied by resistance genotype, being higher with the Klebsiella pneumoniae carbapenemase (KPC) for CZA, lower with metallo-beta-lactamases for CFDC and CZA, and higher with the beta-lactamase CTX-M for ERV. Percent susceptible also varied by global region for CZA (lower in Asia-Pacific) and by U.S. region for ERV (lower in the South and Southeast). Although resistance to comparators often predicted reduced susceptibility to a primary agent (especially CFDC and CZA), even among comparator-resistant isolates the primary-agent-susceptible fraction usually exceeded 50%. These findings clarify the likely utility of CFDC, CZA, and ERV against CR E. coli in relation to multiple bacterial characteristics and geographical region.

Original languageEnglish (US)
Article numbere00797
JournalAntimicrobial agents and chemotherapy
Volume64
Issue number10
DOIs
StatePublished - Oct 2020

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 number 2I01CX000920-04 (J.R.J.). The funders had no control over the content of the report or the decision to publish.

Keywords

  • Carbapenem resistant
  • Cefiderocol
  • Ceftazidime-avibactam
  • Coresistance
  • E. coli
  • Eravacycline
  • KPC
  • MIC
  • Metallo-beta-lactamase
  • ST131-H30

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