Papp-Wallace Krisztina M, Sader Helio S, Maher Joshua M, Kimbrough John H, Castanheira Mariana
JMI Laboratories/Element-Iowa City, North Liberty, Iowa, USA.
Open Forum Infect Dis. 2025 Apr 25;12(5):ofaf250. doi: 10.1093/ofid/ofaf250. eCollection 2025 May.
Carbapenem-resistant Enterobacterales (CREs) are a major public health threat because treatment options are limited. The predominant resistance mechanism in CREs is the production of carbapenemases. Aztreonam-avibactam was shown to possess activity against CREs with class A, B, and D carbapenemases. Herein, the activity of aztreonam-avibactam and comparators were evaluated against Enterobacterales collected between 2017 and 2022 in the United States.
Antimicrobial susceptibility testing for aztreonam-avibactam, ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, cefiderocol, tigecycline, and colistin was conducted using the reference broth microdilution method. Isolates resistant to imipenem or meropenem were defined as carbapenem-resistant, underwent whole-genome sequencing, and were analyzed for the presence of carbapenemase genes.
Of the 54 576 Enterobacterales, 0.9% were CREs and only 3.7% of the CREs were susceptible to aztreonam; the addition of avibactam increased susceptibility to 98.4% based on EUCAST breakpoints. Cefiderocol and tigecycline were the next most potent agents, inhibiting 94.7% of the CREs at current breakpoints. Whole-genome sequencing analysis of the CREs revealed that 82.6% carried a carbapenemase with 360 isolates having only a class A carbapenemase. KPC-encoding genes were the predominant carbapenemase genes identified with 50.4% found in CREs from New York, New Jersey, and Pennsylvania. Aztreonam-avibactam was highly active against CREs carrying class A, B, and/or D carbapenemases with susceptibility rates of 99.4%, 98.0%, and 100%, respectively. Moreover, 94.4% of isolates with no carbapenemases detected were susceptible to aztreonam-avibactam.
Aztreonam-avibactam demonstrates potent activity toward CREs with different carbapenem-resistance mechanisms. The combination is an anticipated welcome addition to the clinician's toolbox giving physicians another option to treat CREs.
耐碳青霉烯类肠杆菌科细菌（CREs）是主要的公共卫生威胁，因为治疗选择有限。CREs中主要的耐药机制是碳青霉烯酶的产生。氨曲南-阿维巴坦对携带A类、B类和D类碳青霉烯酶的CREs具有活性。在此，评估了氨曲南-阿维巴坦及对照药物对2017年至2022年在美国收集的肠杆菌科细菌的活性。
采用参考肉汤微量稀释法对氨曲南-阿维巴坦、头孢他啶-阿维巴坦、亚胺培南-瑞来巴坦、美罗培南-法硼巴坦、头孢地尔、替加环素和黏菌素进行药敏试验。对亚胺培南或美罗培南耐药的菌株定义为耐碳青霉烯类，进行全基因组测序，并分析碳青霉烯酶基因的存在情况。
在54576株肠杆菌科细菌中，0.9%为CREs，仅3.7%的CREs对氨曲南敏感；根据欧洲药敏试验委员会（EUCAST）的断点，加入阿维巴坦后敏感性增至98.4%。头孢地尔和替加环素是其次最有效的药物，在当前断点下抑制94.7%的CREs。对CREs的全基因组测序分析显示，82.6%携带碳青霉烯酶，360株仅携带A类碳青霉烯酶。编码KPC的基因是鉴定出的主要碳青霉烯酶基因，在来自纽约、新泽西和宾夕法尼亚的CREs中占50.4%。氨曲南-阿维巴坦对携带A类、B类和/或D类碳青霉烯酶的CREs具有高活性，敏感性率分别为99.4%、98.0%和100%。此外,94.4%未检测到碳青霉烯酶的菌株对氨曲南-阿维巴坦敏感。
氨曲南-阿维巴坦对具有不同碳青霉烯耐药机制的CREs显示出强大活性。该联合用药是临床医生工具库中预期受欢迎的补充，为医生治疗CREs提供了另一种选择。
