ArticleThe Journal of antimicrobial chemotherapy2022
Evolution of β-lactamase-mediated cefiderocol resistance.
Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 53 citations in OpenAlex.
- Intrinsic resistance networks shape cefiderocol susceptibility in ST258Antimicrobial agents and chemotherapy · 2026Article
- Molecular Characterization and In Silico Functional Insights into Carbapenem Resistance in ClinicalPathogens (Basel, Switzerland) · 2026Article
- Characterization of KPC-160, a novel Ω-loop-deleted KPC variant on a dual-copy plasmid that confers cefiderocol resistance.Antimicrobial agents and chemotherapy · 2026Article
- Combinatorial effects of a novel SHV-248 variant, NDM-5, andMicrobiology spectrum · 2026Article
- Update on the comparativeJAC-antimicrobial resistance · 2026Article
- Article
- Cefiderocol activity against multidrug-resistant isolates from the PERSEUS study: relationship between cefiderocol minimum inhibitory concentration and clinical outcomes.The Journal of antimicrobial chemotherapy · 2026Article
- Small colony variants and cefiderocol resistance in clinicalFrontiers in microbiology · 2026Article
- Article
- Siderophore cephalosporins.EcoSal Plus · 2025Review
- The dual implications of iron homeostasis as a bacterial threat: its roles in virulence and antimicrobial resistance.Archives of microbiology · 2025Review
- Cefiderocol: A Comprehensive Review of Chemistry, Mechanisms of Resistance, and Clinical Applications in the Era of Multidrug Resistance.Current microbiology · 2025Review
- Sporadic cefiderocol resistance in Escherichia coli from the United Arab Emirates involves multifactorial mechanisms reversible by novel beta-lactamase inhibitors.Scientific reports · 2025Article
- Exploring mutational possibilities of KPC variants to reach high level resistance to cefiderocol.Scientific reports · 2025Article
- Copy number flexibility facilitates heteroresistance to increasing antibiotic pressure and threatens the beta-lactam pipeline.Nature communications · 2025Article
- Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review.JAC-antimicrobial resistance · 2025Review
- Combating Metallo-β-Lactamase-ProducingAntibiotics (Basel, Switzerland) · 2025Article
- Carbapenem-resistant Gram-negative bacteria exhibiting clinically undetected cefiderocol heteroresistance leads to treatment failure in a murine model of infection.Frontiers in microbiology · 2025Article
- Insights intoFrontiers in microbiology · 2025Article
- Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to Cefiderocol.Current issues in molecular biology · 2024Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundCefiderocol is a novel siderophore β-lactam with improved hydrolytic stability toward β-lactamases, including carbapenemases, achieved by combining structural moieties of two clinically efficient cephalosporins, ceftazidime and cefepime. Consequently, cefiderocol represents a treatment alternative for infections caused by MDR Gram-negatives.
objectivesTo study the role of cefiderocol on resistance development and on the evolution of β-lactamases from all Ambler classes, including KPC-2, CTX-M-15, NDM-1, CMY-2 and OXA-48.
methodsDirected evolution, using error-prone PCR followed by selective plating, was utilized to investigate how the production and the evolution of different β-lactamases cause changes in cefiderocol susceptibility determined using microbroth dilution assays (MIC and IC50).
resultsWe found that the expression of blaOXA-48 did not affect cefiderocol susceptibility. On the contrary, the expression of blaKPC-2, blaCMY-2, blaCTX-M-15 and blaNDM-1 substantially reduced cefiderocol susceptibility by 4-, 16-, 8- and 32-fold, respectively. Further, directed evolution on these enzymes showed that, with the acquisition of only 1-2 non-synonymous mutations, all β-lactamases were evolvable to further cefiderocol resistance by 2- (NDM-1, CTX-M-15), 4- (CMY-2), 8- (OXA-48) and 16-fold (KPC-2). Cefiderocol resistance development was often associated with collateral susceptibility changes including increased resistance to ceftazidime and ceftazidime/avibactam as well as functional trade-offs against different β-lactam drugs.
conclusionsThe expression of contemporary β-lactamase genes can potentially contribute to cefiderocol resistance development and the acquisition of mutations in these genes results in enzymes adapting to increasing cefiderocol concentrations. Resistance development caused clinically important cross-resistance, especially against ceftazidime and ceftazidime/avibactam.
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