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Antibiotics
Special Issues
Carbapenem-Resistant Enterobacteriaceae: Epidemiology, Detection and Treatment
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Carbapenem-Resistant Enterobacteriaceae: Epidemiology, Detection and Treatment

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (20 May 2025) | Viewed by 1617

Special Issue Editor

Dr. Seung Soon Lee

E-Mail Website
Guest Editor
Division of Infectious Diseases, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea
Interests: gut microbiome; microbiome-based therapeutics; antibiotic-resistant gram-negative bacterial infections

Special Issue Information

Dear Colleagues,

Enterobacteriaceae are a group of bacteria (germs) that are a normal part of the human and animal gut, but they can also cause infections. Carbapenem-resistant Enterobacteriaceae (CRE) are germs resistant to one or several carbapenem antibiotics. Infections caused by CRE have limited treatment options and are associated with a high mortality rate.

This Special Issue welcomes all submissions related to carbapenem-resistant Enterobacteriaceae and aims to develop more effective antibiotic stewardship and infection control measures, promote advances in the treatment of carbapenem-resistant Enterobacteriaceae, and prevent the further spread of carbapenem resistance in Enterobacteriaceae.

Dr. Seung Soon Lee
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • carbapenem-resistant Enterobacterales (CRE)
  • antibiotic treatment
  • epidemiology

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Published Papers (1 paper)

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Research

21 pages, 1308 KB  
Article
Mechanisms of Cefiderocol Resistance in Carbapenemase-Producing Enterobacterales: Insights from Comparative Genomics
by Alexander Tristancho-Baró, Ana Isabel López-Calleja, Ana Milagro, Mónica Ariza, Víctor Viñeta, Blanca Fortuño, Concepción López, Miriam Latorre-Millán, Laura Clusa, David Badenas-Alzugaray, Rosa Martínez, Carmen Torres and Antonio Rezusta
Antibiotics 2025, 14(7), 703; https://doi.org/10.3390/antibiotics14070703 - 12 Jul 2025
Cited by 2 | Viewed by 1183
Abstract
Background/Objectives: Cefiderocol is a novel siderophore cephalosporin with potent in vitro activity against a broad spectrum of Gram-negative bacteria, including carbapenemase-producing Enterobacterales (CPE). However, the recent emergence of resistance in clinical settings raises important concerns regarding its long-term effectiveness. This study aims [...] Read more.
Background/Objectives: Cefiderocol is a novel siderophore cephalosporin with potent in vitro activity against a broad spectrum of Gram-negative bacteria, including carbapenemase-producing Enterobacterales (CPE). However, the recent emergence of resistance in clinical settings raises important concerns regarding its long-term effectiveness. This study aims to investigate the genomic determinants associated with cefiderocol resistance in CPE isolates of human origin. Methods: Comparative genomic analyses were conducted between cefiderocol-susceptible and -resistant CPE isolates recovered from human clinical and epidemiological samples at a tertiary care hospital. Whole-genome sequencing, variant annotation, structural modelling, and pangenome analysis were performed to characterize resistance mechanisms. Results: A total of 59 isolates (29 resistant and 30 susceptible) were analyzed, predominantly comprising Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae. The most frequent carbapenemase gene among the resistant isolates was blaNDM, which was also present in a subset of susceptible strains. The resistant isolates exhibited a significantly higher burden of non-synonymous mutations in their siderophore receptor genes, notably within fecR, fecA, fiu, and cirA. Structural modelling predicted deleterious effects for mutations such as fecR:G104S and fecA:A190T. Additionally, porin loss and loop 3 insertions (e.g., GD/TD) in OmpK36, as well as OmpK35 truncations, were more frequent in the resistant isolates, particularly in high-risk clones such as ST395 and ST512. Genes associated with toxin–antitoxin systems (chpB2, pemI) and a hypothetical metalloprotease (group_2577) were uniquely found in the resistant group. Conclusions: Cefiderocol resistance in CPE appears to be multifactorial. NDM-type metallo-β-lactamases and missense mutations in siderophore uptake systems—especially in those encoded by fec, fhu, and cir operons—play a central role. These may be further potentiated by alterations in membrane permeability, such as porin disruption and efflux deregulation. The integration of genomic and structural approaches provides valuable insights into emerging resistance mechanisms and may support the development of diagnostic tools and therapeutic strategies. Full article
(This article belongs to the Special Issue Carbapenem-Resistant Enterobacteriaceae: Epidemiology, Detection and Treatment)
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