Liu Xinmeng, Li Ziyao, Zhang Feilong, Yang Xinrui, Lei Zichen, Li Chen, Wu Yongli, Zhao Jiankang, Zhang Yulin, Hu Yanning, Shen FangFang, Wang Pingbang, Yang Junwen, Liu Yulei, Shi Huihui, Lu Binghuai
Peking University China-Japan Friendship School of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China; Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China; China-Japan Friendship Institute of Clinical Medical Sciences, Beijing, China; Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China; Changping Laboratory, Beijing, China.
Int J Antimicrob Agents. 2025 Feb;65(2):107407. doi: 10.1016/j.ijantimicag.2024.107407. Epub 2024 Dec 11.
To date, the global prevalence of New Delhi metallo-β-lactamase (NDM) in carbapenem-resistant Enterobacterales (CRE) has been of concern, which is not inhibited by classical β-lactamase inhibitors (BLIs). In this study, we investigated the newly developed antimicrobial agents or inhibitors against NDM-producing Enterobacterales (NPEs).
The in vitro activities of cefiderocol, cefepime/taniborbactam, meropenem/taniborbactam, cefepime/zidebactam, meropenem/nacubactam, aztreonam/nacubactam and aztreonam/avibactam were analyzed in 204 NPE strains collected in China. The potential resistance mechanisms were identified by whole genome sequencing.
Of 204 NPE strains, 18.1% (37/204) were resistant to cefiderocol, in which cirA deleterious alteration, PBP3 insertion and NDM production were taken as potential resistance mechanisms; 28.9% (59/204) were resistant to cefepime/zidebactam, involving K. pneumoniae with ompK35 deleterious alteration; 22.5% (46/204) were resistant to cefepime/taniborbactam, in which YRIN or YRIK inserted in PBP3 and altered ompC are more frequently detected in the resistant E. coli isolates; 27.9% (57/204) were resistant to meropenem/taniborbactam. Aztreonam/avibactam and aztreonam/nacubactam exhibited excellent activity against NPE. However, meropenem/nacubactam had the lowest activity, with only 49.0% (100/204) of all isolates having MICs of <4/4 mg/L.
Aztreonam/avibactam and aztreonam/nacubactam showed the highest activity against NPE. The potential resistance mechanisms of novel antimicrobial agents against NPE should be under active surveillance.
迄今为止，耐碳青霉烯类肠杆菌科细菌（CRE）中新型德里金属β-内酰胺酶（NDM）的全球流行情况令人担忧，这类酶不受经典β-内酰胺酶抑制剂（BLIs）抑制。在本研究中，我们调查了针对产NDM肠杆菌科细菌（NPEs）新开发的抗菌药物或抑制剂。
分析了在中国收集的204株NPE菌株中头孢地尔、头孢吡肟/他尼硼巴坦、美罗培南/他尼硼巴坦、头孢吡肟/齐他西巴坦、美罗培南/那西巴坦、氨曲南/那西巴坦和氨曲南/阿维巴坦的体外活性。通过全基因组测序确定潜在的耐药机制。
在204株NPE菌株中，18.1%（37/204）对头孢地尔耐药，其中cirA有害改变、PBP3插入和NDM产生被视为潜在耐药机制；28.9%（59/204）对头孢吡肟/齐他西巴坦耐药，涉及具有ompK35有害改变的肺炎克雷伯菌；22.5%（46/204）对头孢吡肟/他尼硼巴坦耐药，其中在耐药大肠杆菌分离株中更频繁检测到插入PBP3的YRIN或YRIK以及改变的ompC；27.9%（57/204）对美罗培南/他尼硼巴坦耐药。氨曲南/阿维巴坦和氨曲南/那西巴坦对NPE表现出优异活性。然而，美罗培南/那西巴坦活性最低，所有分离株中只有49.0%（100/204）的最低抑菌浓度<4/4 mg/L。
氨曲南/阿维巴坦和氨曲南/那西巴坦对NPE表现出最高活性。应积极监测新型抗菌药物针对NPE的潜在耐药机制。
