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

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.

Keywords: E. coli ST131 H30; antimicrobial therapy; bla(CTX-M) genotype; cefiderocol; ceftazidime-avibactam; eravacycline; extended-spectrum cephalosporin-resistant; minimum inhibitory concentration; multidrug resistance.