ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2022
Progressive Development of Cefiderocol Resistance in Escherichia coli During Therapy is Associated With an Increase in blaNDM-5 Copy Number and Gene Expression.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70 citing papers in PubMed, 102 citations in OpenAlex.
- The global epidemiology and treatment of metallo-β-lactamase-producing gram-negative pathogens.JAC-antimicrobial resistance · 2026Review
- Outbreak of aztreonam-avibactam-resistant NDM-5-producingMicrobiology spectrum · 2026Article
- Intrinsic resistance networks shape cefiderocol susceptibility in ST258Antimicrobial agents and chemotherapy · 2026Article
- Development of a stable low-copy mini F plasmid derivative for evaluating β-lactamase substrate specificity through antimicrobial susceptibility testing.Microbiology spectrum · 2026Article
- Combinatorial effects of a novel SHV-248 variant, NDM-5, andMicrobiology spectrum · 2026Article
- Unraveling Cefiderocol Resistance in NDM- and OXA-48-like Co-ProducingAntibiotics (Basel, Switzerland) · 2026Article
- Susceptibility to novel antimicrobial agents and molecular epidemiology of carbapenem-resistant enterobacterales: a 9-year study in Central China.BMC microbiology · 2026Article
- Clinical and genomic determinants associated with emergent ceftazidime-avibactam plus aztreonam non-susceptibility in ceftazidime-avibactam resistantAntimicrobial agents and chemotherapy · 2026Article
- Genomic signatures of dominant clones and evolutionary divergence ofMicrobial genomics · 2026Article
- EnvZ/OmpR-driven cooperative behavior promotes cefiderocol resistance in a hanging-droplet evolution system.Science advances · 2026Article
- Vitamin B12 promotes cefiderocol resistance and small-colony variants in carbapenem-resistantmBio · 2026Article
- Activity of novel antibiotics against dual metallo-Beta-lactamase producingJAC-antimicrobial resistance · 2026Article
- Genetic and phenotypic characterization of the plasmid-encoded NDM-80 metallo-β-lactamase inFrontiers in microbiology · 2026Article
- ConfrontingInfection and drug resistance · 2026Review
- Small colony variants and cefiderocol resistance in clinicalFrontiers in microbiology · 2026Article
- Microplastics enhance the risk of cross-genus dissemination of carbapenemase resistance plasmids in ICU patients.Frontiers in cellular and infection microbiology · 2026Article
- Efficacy of cefiderocol in combination with xeruborbactam versus taniborbactam against cefiderocol-resistant NDM-producingAntimicrobial agents and chemotherapy · 2025Article
- Article
- Use of Aztreonam-Avibactam with Rapid Eravacycline Step-Down Therapy for a Tibial Septic Non-Union by NDM-ProducingAntibiotics (Basel, Switzerland) · 2025Article
- Evaluating Antibacterial Efficacy of Cefiderocol and Cefepime/Taniborbactam Against OXA-48-Like and NDM-Expressing Enterobacterales: An In-Vitro and In-Silico Approach.Current microbiology · 2025Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAs cefiderocol is increasingly being prescribed in clinical practice, it is critical that we understand key mechanisms contributing to acquired resistance to this agent.
methodsWe describe a patient with acute lymphoblastic leukemia and a New Delhi metallo-ß-lactamase (NDM)-5-producing Escherichia coli intra-abdominal infection in whom resistance to cefiderocol evolved approximately 2 weeks after the start of treatment. Through whole-genome sequencing (WGS), messenger RNA expression studies, and ethylenediaminetetraacetic acid inhibition analysis, we investigated the role of increased NDM-5 production and genetic mutations contributing to the development of cefiderocol resistance, using 5 sequential clinical E. coli isolates obtained from the patient.
resultsIn all 5 isolates, blaNDM-5 genes were identified. The minimum inhibitory concentrations for cefiderocol were 2, 4, and >32 μg/mL for isolates 1-2, 3, and 4-5, respectively. WGS showed that isolates 1-3 contained a single copy of the blaNDM-5 gene, whereas isolates 4 and 5 had 5 and 10 copies of the blaNDM-5 gene, respectively, on an IncFIA/FIB/IncFII plasmid. These findings were correlated with those of blaNDM-5 messenger RNA expression analysis, in which isolates 4 and 5 expressed blaNDM-5 1.7- and 2.8-fold, respectively, compared to, isolate 1. Synergy testing with the combination of ceftazidime-avibactam and aztreonam demonstrated expansion of the zone of inhibition between the disks for all isolates. The patient was successfully treated with this combination and remained infection free 1 year later.
conclusionsThe findings in our patient suggest that increased copy numbers of blaNDM genes through translocation events are used by Enterobacterales to evade cefiderocol-mediated cell death. The frequency of increased blaNDM-5 expression in contributing to cefiderocol resistance needs investigation.
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