Cefiderocol activity against planktonic and biofilm forms of β-lactamase-producing pseudomonas aeruginosa from people with cystic fibrosis

Objectives: Chronic Pseudomonas aeruginosa infections are a leading cause of acute pulmonary exacerbations in people with cystic fibrosis (pwCF). Intrinsic antibiotic resistance and biofilm formation complicate treatment. This study investigates the genomic diversity and cefiderocol efficacy against...

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Main Authors: Giorgia Fabrizio, Mauro Truglio, Ilaria Cavallo, Francesca Sivori, Massimo Francalancia, Rodolfo J. Riveros Cabral, Manola Comar, Maria Trancassini, Daniele Emanuele Compagnino, Fabiana Diaco, Guido Antonelli, Fiorentina Ascenzioni, Giuseppe Cimino, Fulvia Pimpinelli, Enea Gino Di Domenico
格式: Article
語言:英语
出版: Elsevier 2025-06-01
叢編:Journal of Global Antimicrobial Resistance
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在線閱讀:http://www.sciencedirect.com/science/article/pii/S2213716525000827
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author Giorgia Fabrizio
Mauro Truglio
Ilaria Cavallo
Francesca Sivori
Massimo Francalancia
Rodolfo J. Riveros Cabral
Manola Comar
Maria Trancassini
Daniele Emanuele Compagnino
Fabiana Diaco
Guido Antonelli
Fiorentina Ascenzioni
Giuseppe Cimino
Fulvia Pimpinelli
Enea Gino Di Domenico
author_facet Giorgia Fabrizio
Mauro Truglio
Ilaria Cavallo
Francesca Sivori
Massimo Francalancia
Rodolfo J. Riveros Cabral
Manola Comar
Maria Trancassini
Daniele Emanuele Compagnino
Fabiana Diaco
Guido Antonelli
Fiorentina Ascenzioni
Giuseppe Cimino
Fulvia Pimpinelli
Enea Gino Di Domenico
author_sort Giorgia Fabrizio
collection DOAJ
description Objectives: Chronic Pseudomonas aeruginosa infections are a leading cause of acute pulmonary exacerbations in people with cystic fibrosis (pwCF). Intrinsic antibiotic resistance and biofilm formation complicate treatment. This study investigates the genomic diversity and cefiderocol efficacy against planktonic and biofilm-associated forms of P. aeruginosa isolates from pwCF.Methods: Eight P. aeruginosa clinical isolates and three laboratory strains underwent whole genome sequencing (WGS). Biofilm formation was assessed through biomass, cell count, metabolic activity, and extracellular DNA (eDNA). The minimum bactericidal concentration (MBC90) and biofilm eradication concentration (MBEC90) were also determined.Results: WGS revealed significant genomic diversity, identifying ten distinct sequence types (STs). Antibiotic susceptibility testing (AST) showed that 10/11 strains were susceptible to cefiderocol, with one isolate (MPA9) displaying resistance linked to the blaOXA486 gene. Adding the β-lactamase inhibitor avibactam (AVI) restored susceptibility in this resistant strain. Although iron metabolism genes were highly conserved across isolates, MPA9 lacked the fpvA iron receptor, potentially contributing to cefiderocol resistance. Biofilm formation significantly increased tolerance to cefiderocol, with an 8-fold rise in MBEC90 compared to MBC90.Conclusion: These findings highlight the genomic diversity and adaptive potential of P. aeruginosa in pwCF. Cefiderocol shows promise against planktonic and biofilm-associated P. aeruginosa, and combining it with AVI may counteract β-lactamase-mediated resistance.
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spelling doaj-art-4e4a7ecbbaa341cfad619ec00ae496b42025-06-27T05:50:26ZengElsevierJournal of Global Antimicrobial Resistance2213-71652025-06-0143111119Cefiderocol activity against planktonic and biofilm forms of β-lactamase-producing pseudomonas aeruginosa from people with cystic fibrosisGiorgia Fabrizio0Mauro Truglio1Ilaria Cavallo2Francesca Sivori3Massimo Francalancia4Rodolfo J. Riveros Cabral5Manola Comar6Maria Trancassini7Daniele Emanuele Compagnino8Fabiana Diaco9Guido Antonelli10Fiorentina Ascenzioni11Giuseppe Cimino12Fulvia Pimpinelli13Enea Gino Di Domenico14Department of Biology and Biotechnology ''C. Darwin'', Sapienza University of Rome, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute, IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute, IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute, IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute, IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute, IRCCS, Rome, ItalyInstitute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy; Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy; Microbiology and Virology Unit, A.O.U. Policlinico Umberto I, Rome, ItalyDepartment of Molecular Medicine, Laboratory of Microbiology and Virology, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Laboratory of Microbiology and Virology, Sapienza University of Rome, Rome, ItalyMicrobiology and Virology Unit, A.O.U. Policlinico Umberto I, Rome, Italy; Department of Molecular Medicine, Laboratory of Microbiology and Virology, Sapienza University of Rome, Rome, ItalyDepartment of Biology and Biotechnology ''C. Darwin'', Sapienza University of Rome, Rome, ItalyCystic Fibrosis Regional Reference Center, A.O.U. Policlinico Umberto I, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute, IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy; Corresponding author.Objectives: Chronic Pseudomonas aeruginosa infections are a leading cause of acute pulmonary exacerbations in people with cystic fibrosis (pwCF). Intrinsic antibiotic resistance and biofilm formation complicate treatment. This study investigates the genomic diversity and cefiderocol efficacy against planktonic and biofilm-associated forms of P. aeruginosa isolates from pwCF.Methods: Eight P. aeruginosa clinical isolates and three laboratory strains underwent whole genome sequencing (WGS). Biofilm formation was assessed through biomass, cell count, metabolic activity, and extracellular DNA (eDNA). The minimum bactericidal concentration (MBC90) and biofilm eradication concentration (MBEC90) were also determined.Results: WGS revealed significant genomic diversity, identifying ten distinct sequence types (STs). Antibiotic susceptibility testing (AST) showed that 10/11 strains were susceptible to cefiderocol, with one isolate (MPA9) displaying resistance linked to the blaOXA486 gene. Adding the β-lactamase inhibitor avibactam (AVI) restored susceptibility in this resistant strain. Although iron metabolism genes were highly conserved across isolates, MPA9 lacked the fpvA iron receptor, potentially contributing to cefiderocol resistance. Biofilm formation significantly increased tolerance to cefiderocol, with an 8-fold rise in MBEC90 compared to MBC90.Conclusion: These findings highlight the genomic diversity and adaptive potential of P. aeruginosa in pwCF. Cefiderocol shows promise against planktonic and biofilm-associated P. aeruginosa, and combining it with AVI may counteract β-lactamase-mediated resistance.http://www.sciencedirect.com/science/article/pii/S2213716525000827Cystic fibrosisPseudomonas aeruginosaCefiderocolBiofilmAvibactam
spellingShingle Giorgia Fabrizio
Mauro Truglio
Ilaria Cavallo
Francesca Sivori
Massimo Francalancia
Rodolfo J. Riveros Cabral
Manola Comar
Maria Trancassini
Daniele Emanuele Compagnino
Fabiana Diaco
Guido Antonelli
Fiorentina Ascenzioni
Giuseppe Cimino
Fulvia Pimpinelli
Enea Gino Di Domenico
Cefiderocol activity against planktonic and biofilm forms of β-lactamase-producing pseudomonas aeruginosa from people with cystic fibrosis
Journal of Global Antimicrobial Resistance
Cystic fibrosis
Pseudomonas aeruginosa
Cefiderocol
Biofilm
Avibactam
title Cefiderocol activity against planktonic and biofilm forms of β-lactamase-producing pseudomonas aeruginosa from people with cystic fibrosis
title_full Cefiderocol activity against planktonic and biofilm forms of β-lactamase-producing pseudomonas aeruginosa from people with cystic fibrosis
title_fullStr Cefiderocol activity against planktonic and biofilm forms of β-lactamase-producing pseudomonas aeruginosa from people with cystic fibrosis
title_full_unstemmed Cefiderocol activity against planktonic and biofilm forms of β-lactamase-producing pseudomonas aeruginosa from people with cystic fibrosis
title_short Cefiderocol activity against planktonic and biofilm forms of β-lactamase-producing pseudomonas aeruginosa from people with cystic fibrosis
title_sort cefiderocol activity against planktonic and biofilm forms of β lactamase producing pseudomonas aeruginosa from people with cystic fibrosis
topic Cystic fibrosis
Pseudomonas aeruginosa
Cefiderocol
Biofilm
Avibactam
url http://www.sciencedirect.com/science/article/pii/S2213716525000827
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