ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1670179
This article is part of the Research TopicDefending the Last Line: Combatting Carbapenem-Resistant PathogensView all articles
In vitro antimicrobial activity and resistance mechanisms of cefiderocol against clinical Carbapenem-resistant Gram-negative bacteria
Provisionally accepted
- 1Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Jiangsu, China, Nanjing Drum Tower Hospital, Nanjing, China
- 2Nanjing Municipal Centre for Disease Control and Prevention, Nanjing municipal Key Laboratory of Public Health Testing, Nanjing, Jiangsu 210003, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China
- 3Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang-212013, P.R. China., Jiangsu University, Zhenjiang, China
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Background: The rise of carbapenem-resistant Gram-negative bacteria (CRGNB) necessitates new therapeutic options such as cefiderocol. Objective: To evaluate the in vitro efficacy of cefiderocol against clinical CRGNB and investigate associated resistance mechanisms. Methods: A total of 370 CRGNB isolates were analyzed. Minimum inhibitory concentration (MIC) values were determined, and whole genome sequencing, efflux pump inhibition assays, and RT-qPCR were conducted to assess resistance-related mutations, gene loss, and expression changes. Results: Cefiderocol demonstrated potent in vitro activity, with high susceptibility rates in C. freundii (100%), K. pneumoniae (93.3%), and E. hormaechei (92.2%), and notable activity against P. aeruginosa (80.0%) and E. coli (76.8%). Efflux pump inhibition by Carbonyl Cyanide m-Chlorophenyl Hydrazone (CCCP) significantly reduced MICs in resistant strains. Key resistance mechanisms included β-lactamase gene variants (blaOXA-66, blaOXA-23, blaSHV-12), mutations in envZ, cirA, nuoC, ampC, and loss or altered expression of iron transporter genes (piuA, pirA, fepA). Conclusion: Cefiderocol is highly effective against CRGNB; however, resistance may arise through diverse mechanisms, including efflux pump activity. Continued surveillance of emerging resistance is essential to guide its optimal clinical use.
Keywords: cefiderocol, Carbapenem-resistant Gram-negative bacteria, Antimicrobial susceptibility, resistance mechanisms, efflux pump inhibitor, Mutation
Received: 21 Jul 2025; Accepted: 08 Sep 2025.
Copyright: © 2025 Yan, Ji, Wang, Zou, Shen, Yuan and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoli Cao, Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Jiangsu, China, Nanjing Drum Tower Hospital, Nanjing, China
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