Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to Cefiderocol

In recent years, novel antimicrobials have been developed to counter the emergence of antimicrobial resistance and provide effective therapeutic options against multidrug-resistant (MDR) Gram-negative bacilli (GNB). Cefiderocol, a siderophore cephalosporin, represents a novel valuable antimicrobial...

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Main Authors: Gabriele Bianco, Matteo Boattini, Monica Cricca, Lucia Diella, Milo Gatti, Luca Rossi, Michele Bartoletti, Vittorio Sambri, Caterina Signoretto, Rossella Fonnesu, Sara Comini, Paolo Gaibani
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/46/12/846
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author Gabriele Bianco
Matteo Boattini
Monica Cricca
Lucia Diella
Milo Gatti
Luca Rossi
Michele Bartoletti
Vittorio Sambri
Caterina Signoretto
Rossella Fonnesu
Sara Comini
Paolo Gaibani
author_facet Gabriele Bianco
Matteo Boattini
Monica Cricca
Lucia Diella
Milo Gatti
Luca Rossi
Michele Bartoletti
Vittorio Sambri
Caterina Signoretto
Rossella Fonnesu
Sara Comini
Paolo Gaibani
author_sort Gabriele Bianco
collection DOAJ
description In recent years, novel antimicrobials have been developed to counter the emergence of antimicrobial resistance and provide effective therapeutic options against multidrug-resistant (MDR) Gram-negative bacilli (GNB). Cefiderocol, a siderophore cephalosporin, represents a novel valuable antimicrobial drug for the treatment of infections caused by MDR-GNB. The mechanism of cefiderocol to penetrate through the outer membrane of bacterial cells, termed “<i>Trojan horse</i>”, makes this antimicrobial drug unique and immune to the various resistance strategies adopted by GNB. Its broad spectrum of action, potent antibacterial activity, pharmacokinetics properties, safety, and tolerability make cefiderocol a key drug for the treatment of infections due to MDR strains. Although this novel antimicrobial molecule contributed to revolutionizing the therapeutic armamentarium against MDR-GNB, the recent emergence of cefiderocol-resistant strains has redefined its role in clinical practice and required new strategies to preserve its antibacterial activity. In this review, we provide an updated discussion regarding the mechanism of action, emerging mechanisms of resistance, pharmacokinetic/pharmacodynamic (PK/PD) properties, and efficacy data of cefiderocol against the major Gram-negative bacteria and future prospects.
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spelling doaj-art-a8298d04109049cc90e757ccee2d28ba2025-08-20T02:00:25ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452024-12-014612141321415310.3390/cimb46120846Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to CefiderocolGabriele Bianco0Matteo Boattini1Monica Cricca2Lucia Diella3Milo Gatti4Luca Rossi5Michele Bartoletti6Vittorio Sambri7Caterina Signoretto8Rossella Fonnesu9Sara Comini10Paolo Gaibani11Department of Experimental Medicine, University of Salento, 73100 Lecce, ItalyDepartment of Public Health and Paediatrics, University of Torino, 10124 Turin, ItalyDepartment of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum, Section Microbiology, University of Bologna, 40138 Bologna, ItalyDepartment of Biomedical Sciences, Humanitas University, 20089 Milan, ItalyDepartment of Medical and Surgical Sciences, Alma Mater Studiorum, Section Pharmacology, University of Bologna, 40138 Bologna, ItalyDepartment of Diagnostics and Public Health, Microbiology Section, Verona University, 37134 Verona, ItalyDepartment of Biomedical Sciences, Humanitas University, 20089 Milan, ItalyDepartment of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum, Section Microbiology, University of Bologna, 40138 Bologna, ItalyDepartment of Diagnostics and Public Health, Microbiology Section, Verona University, 37134 Verona, ItalyMicrobiology and Virology Unit, Azienda Ospedaliera Universitaria Integrata Di Verona, 37134 Verona, ItalyOperative Unit of Clinical Pathology, Carlo Urbani Hospital, 60035 Jesi, ItalyDepartment of Diagnostics and Public Health, Microbiology Section, Verona University, 37134 Verona, ItalyIn recent years, novel antimicrobials have been developed to counter the emergence of antimicrobial resistance and provide effective therapeutic options against multidrug-resistant (MDR) Gram-negative bacilli (GNB). Cefiderocol, a siderophore cephalosporin, represents a novel valuable antimicrobial drug for the treatment of infections caused by MDR-GNB. The mechanism of cefiderocol to penetrate through the outer membrane of bacterial cells, termed “<i>Trojan horse</i>”, makes this antimicrobial drug unique and immune to the various resistance strategies adopted by GNB. Its broad spectrum of action, potent antibacterial activity, pharmacokinetics properties, safety, and tolerability make cefiderocol a key drug for the treatment of infections due to MDR strains. Although this novel antimicrobial molecule contributed to revolutionizing the therapeutic armamentarium against MDR-GNB, the recent emergence of cefiderocol-resistant strains has redefined its role in clinical practice and required new strategies to preserve its antibacterial activity. In this review, we provide an updated discussion regarding the mechanism of action, emerging mechanisms of resistance, pharmacokinetic/pharmacodynamic (PK/PD) properties, and efficacy data of cefiderocol against the major Gram-negative bacteria and future prospects.https://www.mdpi.com/1467-3045/46/12/846antimicrobialscefiderocolin vitro activitymultidrug resistanceGram-negativeemerging resistance
spellingShingle Gabriele Bianco
Matteo Boattini
Monica Cricca
Lucia Diella
Milo Gatti
Luca Rossi
Michele Bartoletti
Vittorio Sambri
Caterina Signoretto
Rossella Fonnesu
Sara Comini
Paolo Gaibani
Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to Cefiderocol
Current Issues in Molecular Biology
antimicrobials
cefiderocol
in vitro activity
multidrug resistance
Gram-negative
emerging resistance
title Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to Cefiderocol
title_full Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to Cefiderocol
title_fullStr Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to Cefiderocol
title_full_unstemmed Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to Cefiderocol
title_short Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to Cefiderocol
title_sort updates on the activity efficacy and emerging mechanisms of resistance to cefiderocol
topic antimicrobials
cefiderocol
in vitro activity
multidrug resistance
Gram-negative
emerging resistance
url https://www.mdpi.com/1467-3045/46/12/846
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