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.

超广谱头孢菌素耐药大肠杆菌(ESCREC) 的威胁日益严重。主要的 ESCREC 谱系包括序列类型 ST131，尤其是其（bla _CTX-M-15相关）H 30Rx 亚克隆和H 30R1 亚克隆内的（ bla _CTX-M-27相关）C1-M27 子集。针对此类替代抗菌剂菌株（包括最近开发的氨基糖苷类普拉佐霉素）的比较活性尚未确定，因此在此进行了研究。我们评估了 plazomicin 和 11 个比较剂对 216 个特征明确的 ESCREC 分离株（明尼苏达州，2012-2017 年）的活性，然后将肉汤微量稀释 MIC 与系统发育和克隆背景、β-内酰胺酶基因型（bla _CTX-M；第 1 组和第 9 组变体）进行比较，并共同抵抗。对普拉佐米星、美罗培南、亚胺培南和替加环素的敏感率> 99%；阿米卡星和厄他培南为 96–98%；其余比较器 ≤ 75%。对于大多数比较者来说，MIC 与多种细菌特征相关，在特定药物模式中存在显着差异。相比之下，对于普拉佐米星，唯一与 MIC 显着相关的细菌特征是 ST131 亚克隆：普拉佐米星 MIC 在 O16 ST131 分离株中最低，在 ST131- H 30R1 C1-M27 亚克隆分离株中最高。此外，仅阿米卡星和左氧氟沙星对比较药物的耐药性和敏感性方面，普拉佐米星 MIC 存在显着差异。对于大多数研究药物，针对 ESCREC 的抗菌活性与多种细菌特征（包括克隆背景）相关，差异很大，而对于普拉佐米星，其抗菌活性仅因 ST131 亚克隆而变化（C1-M27 分离株最不敏感，O16 分离株最敏感）。这些发现支持普拉佐米星作为治疗 ESCREC 感染的可靠替代品，并敦促继续关注 C1-M27 ST131 亚克隆。