Cefiderocol: An Overview of Antibacterial Activity and Resistance Mechanisms

A Special Issue of Microorganisms (ISSN 2076-2607) belonging to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 284

Editor

Special Issue Information

Dear Colleagues,

The rapid spread of carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) has prompted researchers to develop new drugs such as cefiderocol (FDC), ceftazidime-avibactam, imipenem-relebactam and meropenem-varbobactam, which exhibit activity against carbapenem-resistant Gram-negative bacteria. FDC is a novel siderophore cephalosporin, used to treat septicemia, nosocomial pneumonia and complicated urinary-tract infections,  which uses the ferric ion transport system enabling active uptake, bypassing the outer membrane of Gram-negative bacteria.  In contrast to β-lactam-inhibitor combinations, FDC demonstrates increased activity against Gram-negative bacteria with all carbapenemase types, including metallo-β-lactamases. It exerts activity against 90% Enterobacterales, P. aeruginosa and A. baumannii.  However, resistance emerged recently, among Enterobacterales positive for NDM and OXA-48 and CRAB. The combination of FDC with other antibiotics such as amikacin or colistin was shown to improve its activity and prevent the development of heteroresistance.

The aim of this Special Issue is to collect information about its antibacterial activity, stability to β-lactamases, including carbapenemases, therapeutic effectiveness and molecular epidemiology of resistant isolates.

We welcome manuscript submissions related to the following topics for the Special Issue:

  1. Antibacterial activity of cefiderocol;

  2. Resistance mechanisms and resistance trends;

  3. Molecular epidemiology of cefiderocol resistance;

  4. Laboratory analysis of antibacterial activity and resistance traits;

  5. Clinical trials.

Types of articles: research articles, reviews.

Prof. Dr. Branka Bedenic
Guest Editor

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Keywords

  • cefiderocol
  • carbapenemases
  • gram-negative bacteria
  • NDM
  • OXA-48

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Published Papers (1 paper)

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Research

32 pages, 2802 KB  
Article
Paired In Vitro Susceptibility of Cefiderocol and Colistin in Colistin-Resistant, Extensively Drug-Resistant Gram-Negative Bacilli: A Single-Centre, MIC-Based Analysis of 236 Clinical Isolates
by Elena Hogea, Nicolae Ciprian Pilut, Felix Bratosin, Andra-Nicole Rusnac, Oana Plavitu, Livia Stanga and Horia Silviu Branea
Microorganisms 2026, 14(9), 2071; https://doi.org/10.3390/microorganisms14092071 - 16 Sep 2026
Viewed by 33
Abstract
Extensively drug-resistant (XDR) Gram-negative bacilli increasingly exhaust therapeutic options, leaving colistin and cefiderocol as last-resort agents. We assessed whether cefiderocol retains in vitro activity against colistin-resistant isolates, without inferring clinical efficacy. We analysed 236 non-duplicate XDR Gram-negative isolates from 220 patients. Cefiderocol and [...] Read more.
Extensively drug-resistant (XDR) Gram-negative bacilli increasingly exhaust therapeutic options, leaving colistin and cefiderocol as last-resort agents. We assessed whether cefiderocol retains in vitro activity against colistin-resistant isolates, without inferring clinical efficacy. We analysed 236 non-duplicate XDR Gram-negative isolates from 220 patients. Cefiderocol and colistin MICs were determined via reference broth microdilution with EUCAST-required quality control (iron-depleted broth for cefiderocol; mcr-1-positive Escherichia coli NCTC 13846 for colistin) and interpreted using species-specific EUCAST v16.1 (2026) breakpoints (cefiderocol: Enterobacterales S ≤ 2, I 4, R > 4 mg/L; Pseudomonas aeruginosa S ≤ 2, R > 2 mg/L; colistin: P. aeruginosa S ≤ 4 mg/L). Because EUCAST publishes no clinical cefiderocol breakpoint for Acinetobacter baumannii, the primary analysis comprised species with breakpoints for both agents (n = 150; 126 paired); A. baumannii is reported as an MIC distribution and the pooled 236-isolate comparison as secondary. In the primary analysis, 120/150 isolates (80.0%) were cefiderocol-susceptible at standard or increased exposure. Among paired isolates, cefiderocol covered 77.0% versus 43.7% for colistin; agreement was negligible (Cohen’s κ = 0.020), with 54 isolates favouring cefiderocol and 12 the reverse (McNemar p < 0.001). Conditional in vitro susceptibility among 71 colistin-resistant isolates was 76.1% (95% CI 65.0–84.5), giving 33.3 percentage points of incremental coverage and one additional cefiderocol-susceptible isolate per 2.3 matched isolates tested. Secondary analyses were directionally consistent (incremental coverage 21.8–33.3 points). These in vitro findings support paired testing of both agents to identify isolates retaining cefiderocol activity when colistin does not; clinical benefit was not assessed. Full article
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