Open AccessComparative activity of plazomicin against extended-spectrum cephalosporin-resistant Escherichia coli clinical isolates (2012–2017) in relation to phylogenetic background, sequence type 131 subclones, blaCTX-M genotype, and resistance to comparator agents
Author(s) -
Brian Johnston,
Paul Thuras,
Stephen Porter,
Connie Clabots,
James R. Johnson
Publication year - 2021
Publication title -
european journal of clinical microbiology and infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.154
H-Index - 106
eISSN - 1435-4373
pISSN - 0934-9723
DOI - 10.1007/s10096-021-04256-9
Subject(s) - amikacin , microbiology and biotechnology , biology , aminoglycoside , escherichia coli , genotype , tigecycline , antimicrobial , tobramycin , antibiotics , genetics , gene , gentamicin
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. 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 (bla CTX-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.