Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), the leading cause of extraintestinal E. coli infections globally, threatens therapeutic efficacy. Accordingly, we determined broth microdilution MICs for three distinctive newer agents, i.e., cefiderocol (CFDC), ceftazidime-avibactam (CZA), and eravacycline (ERV), plus 11 comparators, against 343 carbapenem-resistant (CR) clinical E. coli isolates, then compared susceptibility results with bacterial characteristics and region. The collection comprised 203 U.S. isolates (2002 to 2017) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003 to 2017). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant beta-lactamase-encoding genes. CFDC, CZA, and ERV exhibited the highest percent susceptible (82% to 98%) after tigecycline (TGC) (99%); avibactam improved CZA's activity over that of CAZ (11% susceptible). Percent susceptible varied by phylogroup and ST for CFDC and CZA (greatest in phylogroups B2, D, and F, and in ST131, ST405, and ST648). Susceptibility also varied by resistance genotype, being higher with the Klebsiella pneumoniae carbapenemase (KPC) for CZA, lower with metallo-beta-lactamases for CFDC and CZA, and higher with the beta-lactamase CTX-M for ERV. Percent susceptible also varied by global region for CZA (lower in Asia-Pacific) and by U.S. region for ERV (lower in the South and Southeast). Although resistance to comparators often predicted reduced susceptibility to a primary agent (especially CFDC and CZA), even among comparator-resistant isolates the primary-agent-susceptible fraction usually exceeded 50%. These findings clarify the likely utility of CFDC, CZA, and ERV against CR E. coli in relation to multiple bacterial characteristics and geographical region.

中文翻译：

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头孢洛罗，头孢他啶-阿维巴坦和依拉环素对美国和国际站点耐碳青霉烯的大肠埃希菌的克隆背景，抗性基因，抗性和区域性的活性。

大肠杆菌中对碳青霉烯类药物的新兴耐药性，包括序列类型131（ST131），是全球肠外大肠杆菌感染的主要原因，威胁到治疗效果。因此，我们确定了三种独特的新型药物的肉汤微稀释度MIC，即头孢德罗可（CFDC），头孢他啶-avibactam（CZA）和艾拉环素（ERV），以及11种比较物，针对343种耐碳青霉烯（CR）的临床大肠杆菌。分离，然后将敏感性结果与细菌特征和区域进行比较。该集合包括203个美国分离株（2002年至2017年）和141个来自欧洲，拉丁美洲和亚太地区（2003年至2017年）国家的分离株。分离株的特征在于系统发生组，抗性相关序列类型（STs）及其子集以及相关的β-内酰胺酶编码基因。在替加环素（TGC）之后，CFDC，CZA和ERV的易感性百分比最高（82％至98％）（99％）；阿维巴坦比CAZ（易感性11％）提高了CZA的活性。CFDC和CZA的易感百分比随系统群和ST的变化而变化（系统群B2，D和F以及ST131，ST405和ST648中最大）。耐药性基因型也会改变药敏性，肺炎克雷伯菌的敏感性更高碳青霉烯酶（KPC）用于CZA，对于CFDC和CZA，金属β-内酰胺酶较低，而对于ERV，β-内酰胺酶CTX-M较高。CZA的全球区域（亚太地区较低）和ERV的美国区域（南部和东南部较低）的易感百分比也有所不同。尽管对比较剂的抗药性通常预示着对主要药物（尤其是CFDC和CZA）的敏感性降低，但即使在比较剂耐药的菌株中，主要药物的敏感性分数通常也超过50％。这些发现阐明了CFDC，CZA和ERV可能针对多种细菌特征和地理区域针对CR大肠杆菌的效用。