ArticleThe Journal of antibiotics2024
In vitro resistance development gives insights into molecular resistance mechanisms against cefiderocol.
Article in The Journal of antibiotics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Evaluation of cefiderocol trailing and other unclear susceptibility testing endpoints forJournal of clinical microbiology · 2026Article
- Reduced Susceptibility to Cefiderocol Among Clinical MCR-1-ProducingAntibiotics (Basel, Switzerland) · 2026Article
- Intrinsic resistance networks shape cefiderocol susceptibility in ST258Antimicrobial agents and chemotherapy · 2026Article
- KPC-producing Klebsiella pneumoniae in Switzerland from 2024 to 2025: comparative genomics and cefiderocol resistance mechanisms analyses.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Virulence and Resistance Mechanisms in Multidrug-ResistantPathogens (Basel, Switzerland) · 2026Review
- Treatment Options for Metallo-Beta-Lactamase-ProducingInternational journal of molecular sciences · 2026Review
- Article
- High prevalence of blaBMC microbiology · 2026Article
- EnvZ/OmpR-driven cooperative behavior promotes cefiderocol resistance in a hanging-droplet evolution system.Science advances · 2026Article
- Novel Insights into Carbapenem Resistance: Mechanisms, Diagnostics, and Future Directions.Antibiotics (Basel, Switzerland) · 2026Review
- Genetic basis of cefiderocol resistance inMicrobiology spectrum · 2026Article
- Interpretive agreement of susceptibility between broth microdilution and disk diffusion methods for cefiderocol, using criteria from the Clinical and Laboratory Standards Institute, European Committee on Antimicrobial Susceptibility Testing, and the Food and Drug Administration.Journal of clinical microbiology · 2026Article
- Cefiderocol resistance genes identified in environmental samples using functional metagenomics.The ISME journal · 2026Article
- Small colony variants and cefiderocol resistance in clinicalFrontiers in microbiology · 2026Article
- Ferrichrome: bacterial function, synthetic mimics, and biomedical applications.Frontiers in microbiology · 2026Review
- Cefiderocol Susceptibility and Carbapenemase Profiles in Carbapenem-Resistant Enterobacterales.Infectious diseases & clinical microbiology · 2026Article
- Antibiotic Resistance inAntibiotics (Basel, Switzerland) · 2026Review
- Cefiderocol Comparative Resistance and Clinical Predictors in CRE-BSI: Data from an OXA-48-Endemic Region with Rising OXA-48/NDM Coproducers.Antibiotics (Basel, Switzerland) · 2025Article
- Genomic analysis of carbapenem resistant Acinetobacter baumannii outbreak in a burn intensive care unit of a tertiary-care hospital in Madrid, Spain.Antimicrobial resistance and infection control · 2025Article
- Rapid Emergence of Cefiderocol Resistance Associated with Mutation ofAntibiotics (Basel, Switzerland) · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance using an in vitro resistance development model to gain insights into the underlying molecular resistance mechanisms. Cefiderocol susceptible reference strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) and a clinical Acinetobacter baumannii complex isolate were exposed to increasing cefiderocol concentrations using a high-throughput resistance development model. Cefiderocol susceptibility testing was performed using broth microdilution. Whole-genome sequencing was employed to identify newly acquired resistance mutations. Our in vitro resistance development model led to several clones of strains exhibiting cefiderocol resistance, with MIC values 8-fold to 512-fold higher than initial levels. In total, we found 42 different mutations in 26 genes, of which 35 could be described for the first time. Putative loss-of-function mutations were detected in the envZ, tonB, and cirA genes in 13 out of 17 isolates, leading to a decrease in cefiderocol influx. Other potential resistance mechanisms included multidrug efflux pumps (baeS, czcS, nalC), antibiotic-inactivating enzymes (ampR, dacB), and target mutations in penicillin-binding-protein genes (mrcB). This study reveals new insights into underlying molecular resistance mechanisms against cefiderocol. While mutations leading to reduced influx via iron transporters was the most frequent resistance mechanism, we also detected several other novel resistance mutations causing cefiderocol resistance.
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