ArticleChemical science2025
Cefiderocol "under siege"? Understanding the rise of NDM-mediated resistance to novel agents.
Article in Chemical science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed.
- Article
- The Evolving Clonal, Plasmid-Mediated Resistome, Virulome and Therapeutic Landscape of Carbapenem-ResistantAntibiotics (Basel, Switzerland) · 2026Article
- Article
- Intrinsic resistance networks shape cefiderocol susceptibility in ST258Antimicrobial agents and chemotherapy · 2026Article
- Cefiderocol nonsusceptibility among carbapenem-resistantAntimicrobial agents and chemotherapy · 2026Article
- Article
- In Vitro Activity of Imipenem-Funobactam Against Clinical Isolates of Gram-Negative Bacilli.Antibiotics (Basel, Switzerland) · 2026Article
- Comparative activity of ceftibuten combinations with avibactam, ledaborbactam, and xeruborbactam against recombinant β-lactamase-producingAntimicrobial agents and chemotherapy · 2026Article
- Combinatorial effects of a novel SHV-248 variant, NDM-5, andMicrobiology spectrum · 2026Article
- Functional dynamics of water in New Delhi metallo-β-lactamase catalysis.Protein science : a publication of the Protein Society · 2026Article
- The pharmacokinetics/pharmacodynamics index of high-dose tigecycline in patients with carbapenem-resistant Enterobacterales bloodstream infection: a prospective study.BMC infectious diseases · 2026Article
- Unraveling Cefiderocol Resistance in NDM- and OXA-48-like Co-ProducingAntibiotics (Basel, Switzerland) · 2026Article
- Beyond β-Lactams: Defining the Role of Eravacycline in Multidrug-Resistant and Metallo-β-Lactamase-Producing Infections.Antibiotics (Basel, Switzerland) · 2026Review
- Article
- Phenotypic and genotypic characterization of HMB-3, a metallo-beta-lactamase from Pseudomonas asiatica.The Journal of antimicrobial chemotherapy · 2026Article
- Zinc starvation uncovers bacterial host-specific proteases that shape NDM adaptability inmBio · 2026Article
- Innovative Antibiotics: The Experience of Cefiderocol in Carbapenem-Resistant Gram-Negative Infections.Infection and drug resistance · 2026Review
- Emergence of New Delhi Metallo-β-Lactamase 14-Producing Klebsiella pneumoniae Sequence Type 147 Clone in Spain and Outbreak in the Canary Islands.Emerging infectious diseases · 2026Article
- Contribution of mutational resistance mechanisms and acquired β-lactamases to cefiderocol/xeruborbactam susceptibility inAntimicrobial agents and chemotherapy · 2025Article
- Cefiderocol Resistance inAntibiotics (Basel, Switzerland) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
The global spread of antimicrobial resistance (AMR) underscores the critical need for the rapid development of new drugs. Particularly alarming is the surge in metallo-β-lactamases (MBLs) - broad spectrum enzymes able to inactivate penicillins, cephalosporins, and carbapenems. Cefiderocol (FDC), a siderophore-containing cephalosporin, was initially reported as resistant to MBL hydrolysis. Indeed, FDC has been designated as the preferred treatment for Gram-negative pathogens producing MBLs - with the most common MBLs of clinical concern belonging to the NDM, VIM, or IMP families. Regrettably, increasing reports of FDC resistance are emerging. Many of these events are linked to overexpression of NDM, sometimes coupled to alterations in iron transporters, challenging the notion of FDC being invulnerable to MBL hydrolysis. Herein, we demonstrate that NDM-1 and -5 are able to inactivate FDC efficiently, while VIM-2 and IMP-1 show impaired catalytic efficiency against this substrate. All these MBL enzymes form a reversible enzyme-product adduct with FDC, whose lifetime varies considerably among MBLs. In IMP-1 and VIM-2, this results in efficient enzyme inhibition. In contrast, NDM variants are poorly inhibited, eliciting efficient turnover rates. We propose a mechanistic explanation for FDC action that aligns with clinical findings suggesting NDMs contributing to FDC resistance. Based on these conclusions, we suggest caution when using this potent cephalosporin against NDM-producers. FDC paired with an NDM-inhibitor may be a strategy to preserve this important antibiotic.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.