Evidence map›Paper›PMID 41023121›Full record

ArticleScientific reports2025

Sporadic cefiderocol resistance in Escherichia coli from the United Arab Emirates involves multifactorial mechanisms reversible by novel beta-lactamase inhibitors.

Farah Al-Marzooq, Hafsa Ahli, Rauda Aldhaheri, Omar Aleissaee, Abdulrahman Alzaabi, Abdullah Alsaadi, Hamad Almansoori, Akela Ghazawi, Lana Daoud, Amna Ahmad and 1 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Farah Al-MarzooqDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box No. 15551, Al Ain, United Arab Emirates. f.almarzooq@uaeu.ac.ae.
Hafsa AhliDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box No. 15551, Al Ain, United Arab Emirates.
Rauda AldhaheriDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box No. 15551, Al Ain, United Arab Emirates.
Omar AleissaeeDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box No. 15551, Al Ain, United Arab Emirates.
Abdulrahman AlzaabiDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box No. 15551, Al Ain, United Arab Emirates.
Abdullah AlsaadiDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box No. 15551, Al Ain, United Arab Emirates.
Hamad AlmansooriDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box No. 15551, Al Ain, United Arab Emirates.
Akela GhazawiDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box No. 15551, Al Ain, United Arab Emirates.
Lana DaoudDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box No. 15551, Al Ain, United Arab Emirates.
Amna AhmadDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box No. 15551, Al Ain, United Arab Emirates.
Timothy CollynsTawam Hospital, Al Ain, United Arab Emirates.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cefiderocol (CFDC), a novel siderophore-cephalosporin, is effective against multidrug-resistant (MDR) pathogens, but the emergence of resistance threatens its future use in treating infections. This study reports the emergence of CFDC resistance in four E. coli strains isolated from immunocompromised and critically ill patients in the United Arab Emirates, and provides a comprehensive genomic analysis of these strains, aiming to uncover the mechanisms driving this resistance. Whole-genome sequencing with bioinformatic analysis revealed specific beta-lactamase variants (NDM-5, CMY-2/145, and OXA-181) and unique mutations in siderophore-iron transport genes (cirA, fepA, fecA, fiu, and tonB) and penicillin-binding proteins (PBPs) associated with resistance. Phylogenetic analysis showed that the strains were not clonally related, indicating the sporadic nature of resistance. To address this challenge, we evaluated the efficacy of several novel beta-lactamase inhibitors (BLIs) combined with CFDC. In vitro susceptibility testing demonstrated that these inhibitors restored the antibacterial activity of CFDC against resistant strains. Zidebactam, with intrinsic antibacterial activity, caused the most significant reduction in CFDC minimum inhibitory concentrations (MICs), while the activity of other inhibitors (taniborbactam and xeruborbactam) was dependent on the genetic makeup of the strains, especially mutations in the siderophore-iron uptake genes. Our findings underscore the importance of genomic surveillance in deciphering antibiotic resistance mechanisms. Novel BLIs and partner antibiotics could be added weapons in the fight against MDR bacteria; thus, we recommend using combinations with novel BLIs as innovative therapeutic options to combat the emerging threat of CFDC resistance, after proper validation of their in vivo efficacy.

Indexed as

Anti-Bacterial Agentsbeta-Lactamase InhibitorsCephalosporinsDrug Resistance, BacterialEscherichia coliEscherichia coli Infectionsbeta-LactamasesCefiderocolDrug Resistance, Multiple, BacterialEscherichia coli ProteinsHumansMicrobial Sensitivity TestsMutationPhylogenyUnited Arab EmiratesWhole Genome SequencingAnti-Bacterial Agentsbeta-Lactamase Inhibitorsbeta-LactamasesCefiderocolCephalosporinsEscherichia coli ProteinsBeta-lactamase inhibitorsCefiderocolEscherichia coliWhole-genome sequencing

Identifiers

PMID41023121
PMCPMC12480463

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.