Comparative activity of plazomicin against extended-spectrum cephalosporin-resistant Escherichia coli clinical isolates (2012–2017) in relation to phylogenetic background, sequence type 131 subclones, bla CTX-M genotype, and resistance to comparator agents

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

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. The comparative activity against such strains of alternative antimicrobial agents, including the recently developed aminoglycoside plazomicin, is undefined, so was investigated here. We assessed plazomicin and 11 comparators for activity against 216 well-characterized ESCREC isolates (Minnesota, 2012–2017) and then compared broth microdilution MICs with phylogenetic and clonal background, beta-lactamase genotype (blaCTX-M; group 1 and 9 variants), and co-resistance. Percent susceptible was > 99% for plazomicin, meropenem, imipenem, and tigecycline; 96–98% for amikacin and ertapenem; and ≤ 75% for the remaining comparators. For most comparators, MICs varied significantly in relation to multiple bacterial characteristics, in agent-specific patterns. By contrast, for plazomicin, the only bacterial characteristic significantly associated with MICs was ST131 subclone: plazomicin MICs were lowest among O16 ST131 isolates and highest among ST131-H30R1 C1-M27 subclone isolates. Additionally, plazomicin MICs varied significantly in relation to resistance vs. susceptibility to comparator agents only for amikacin and levofloxacin. For most study agents, antimicrobial activity against ESCREC varied extensively in relation to multiple bacterial characteristics, including clonal background, whereas for plazomicin, it varied only by ST131 subclone (C1-M27 isolates least susceptible, O16 isolates most susceptible). These findings support plazomicin as a reliable alternative for treating ESCREC infections and urge continued attention to the C1-M27 ST131 subclone.

Original languageEnglish (US)
Pages (from-to)2069-2075
Number of pages7
JournalEuropean Journal of Clinical Microbiology and Infectious Diseases
Volume40
Issue number10
DOIs
StatePublished - Oct 2021

Bibliographical note

Funding Information:
This work was supported by an investigator-initiated grant from Cipla/Achaogen. This work was also supported by Office of Research and Development, Department of Veterans Affairs and the National Institute of Allergy and Infectious Diseases of the NIH (Antibacterial Resistance Leadership Group, award number UM1AI104681) (JRJ). The sponsors had no role in study design, data collection, data analysis, writing the manuscript, or the decision to publish.

Publisher Copyright:
© 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Keywords

  • Antimicrobial resistance
  • Escherichia coli
  • Extended-spectrum beta-lactamase
  • Extended-spectrum cephalosporins
  • Plazomicin
  • ST131

PubMed: MeSH publication types

  • Journal Article

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