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

doi:10.1016/j.diagmicrobio.2021.115314

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, bla_CTX-M genotype, and coresistance

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

Psychiatry & Behavioral Sciences

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4 Scopus citations

Abstract

Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (bla_CTX-M-15-associated) H30Rx subclone and (bla_CTX-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 (bla_CTX-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 language	English (US)
Article number	115314
Journal	Diagnostic Microbiology and Infectious Disease
Volume	100
Issue number	1
DOIs	https://doi.org/10.1016/j.diagmicrobio.2021.115314
State	Published - 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

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

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Johnston, B. D., Thuras, P., Porter, S. B., Clabots, C., & Johnsona, J. R. (2021). 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, bla_CTX-M genotype, and coresistance. Diagnostic Microbiology and Infectious Disease, 100(1), Article 115314. https://doi.org/10.1016/j.diagmicrobio.2021.115314

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, bla_CTX-M genotype, and coresistance. / Johnston, Brian D; Thuras, Paul; Porter, Stephen B. et al.
In: Diagnostic Microbiology and Infectious Disease, Vol. 100, No. 1, 115314, 05.2021.

Research output: Contribution to journal › Article › peer-review

Johnston, BD, Thuras, P, Porter, SB, Clabots, C & Johnsona, JR 2021, '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, bla_CTX-M genotype, and coresistance', Diagnostic Microbiology and Infectious Disease, vol. 100, no. 1, 115314. https://doi.org/10.1016/j.diagmicrobio.2021.115314

Johnston BD, Thuras P, Porter SB, Clabots C, Johnsona JR. 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, bla_CTX-M genotype, and coresistance. Diagnostic Microbiology and Infectious Disease. 2021 May;100(1):115314. doi: 10.1016/j.diagmicrobio.2021.115314

Johnston, Brian D ; Thuras, Paul ; Porter, Stephen B. et al. / 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, bla_CTX-M genotype, and coresistance. In: Diagnostic Microbiology and Infectious Disease. 2021 ; Vol. 100, No. 1.

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