Cargando…

1715. In Vitro Antibacterial Activity of Cefiderocol against Difficult-to-treat Resistant (DTR) Gram-negative Pathogens in United States from SENTRY Antimicrobial Surveillance Program in 2020/2021

BACKGROUND: Difficult-to-treat resistant (DTR) isolates are defined as resistance to all first-line high-efficacy, low-toxicity antibiotics (penicillins, cephalosporins, carbapenems and quinolones), leaving physicians with limited treatment options. Cefiderocol (CFDC) is a siderophore cephalosporin...

Descripción completa

Detalles Bibliográficos
Autores principales: Yamano, Yoshinori, Takemura, Miki, Shortridge, Dee, Slover, Christine M, Longshaw, Christopher M, Echols, Roger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9752713/
http://dx.doi.org/10.1093/ofid/ofac492.1345
_version_ 1784850794729701376
author Yamano, Yoshinori
Takemura, Miki
Shortridge, Dee
Slover, Christine M
Longshaw, Christopher M
Echols, Roger
Echols, Roger
Echols, Roger
author_facet Yamano, Yoshinori
Takemura, Miki
Shortridge, Dee
Slover, Christine M
Longshaw, Christopher M
Echols, Roger
Echols, Roger
Echols, Roger
author_sort Yamano, Yoshinori
collection PubMed
description BACKGROUND: Difficult-to-treat resistant (DTR) isolates are defined as resistance to all first-line high-efficacy, low-toxicity antibiotics (penicillins, cephalosporins, carbapenems and quinolones), leaving physicians with limited treatment options. Cefiderocol (CFDC) is a siderophore cephalosporin with activity against a wide variety of Gram-negative bacteria, including carbapenem-resistant Enterobacterales and non-fermenters. We evaluated the in vitro activity of cefiderocol against DTR isolates collected in United States as part of SENTRY surveillance program in 2020 and 2021. In vitro susceptibility of cefiderocol and comparator agents to DTR isolates [Figure: see text] METHODS: Susceptibility testing was performed by broth microdilution according to CLSI guidelines. All antibiotics were tested in cation-adjusted Mueller-Hinton broth (CAMHB) except for CFDC, for which iron-depleted CAMHB was used. Susceptibility rate (%) was determined according to CLSI breakpoints, and DTR pathogens were defined as being resistant to cefepime, ceftazidime ceftriaxone (only for Enterobacterales), imipenem, meropenem, ciprofloxacin and levofloxacin according to CLSI/FDA breakpoints. RESULTS: Among a total of 8,328 Enterobacterales, 2,241 Pseudomonas aeruginosa, and 586 Acinetobacter calcoaceticus-baumannii complex (ACB) clinical isolates from the United States, 50 Enterobacterales (0.6%), 36 P. aeruginosa (1.6%) and 114 ACB (19.5%) isolates showed a DTR phenotype, respectively. CFDC demonstrated its potent in vitro activity against these DTR isolates with MIC(90) of ≤4 μg/mL with a susceptibility rate of ≥92% except for DTR ACB based on FDA breakpoint (75.4%). In contrast, MIC(90)s of β-lactam/β-lactamase inhibitor combination drugs showed lower activity (Table). CONCLUSION: Cefiderocol demonstrated potent in vitro activity against DTR isolates of Enterobacterales, P. aeruginosa and ACB, indicating cefiderocol has high potential for treating infections caused by these difficult-to-treat strains. DISCLOSURES: Yoshinori Yamano, PhD, Shionogi: Employee Miki Takemura, n/a, Shionogi: Employee Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Christine M. Slover, PharmD, Shionogi: Employee Christopher M. Longshaw, PhD, Shionogi: Employee Roger Echols, MD, Shionogi: Advisor/Consultant Roger Echols, MD, Shionogi: Advisor/Consultant Roger Echols, MD, Shionogi: Advisor/Consultant.
format Online
Article
Text
id pubmed-9752713
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-97527132022-12-16 1715. In Vitro Antibacterial Activity of Cefiderocol against Difficult-to-treat Resistant (DTR) Gram-negative Pathogens in United States from SENTRY Antimicrobial Surveillance Program in 2020/2021 Yamano, Yoshinori Takemura, Miki Shortridge, Dee Slover, Christine M Longshaw, Christopher M Echols, Roger Echols, Roger Echols, Roger Open Forum Infect Dis Abstracts BACKGROUND: Difficult-to-treat resistant (DTR) isolates are defined as resistance to all first-line high-efficacy, low-toxicity antibiotics (penicillins, cephalosporins, carbapenems and quinolones), leaving physicians with limited treatment options. Cefiderocol (CFDC) is a siderophore cephalosporin with activity against a wide variety of Gram-negative bacteria, including carbapenem-resistant Enterobacterales and non-fermenters. We evaluated the in vitro activity of cefiderocol against DTR isolates collected in United States as part of SENTRY surveillance program in 2020 and 2021. In vitro susceptibility of cefiderocol and comparator agents to DTR isolates [Figure: see text] METHODS: Susceptibility testing was performed by broth microdilution according to CLSI guidelines. All antibiotics were tested in cation-adjusted Mueller-Hinton broth (CAMHB) except for CFDC, for which iron-depleted CAMHB was used. Susceptibility rate (%) was determined according to CLSI breakpoints, and DTR pathogens were defined as being resistant to cefepime, ceftazidime ceftriaxone (only for Enterobacterales), imipenem, meropenem, ciprofloxacin and levofloxacin according to CLSI/FDA breakpoints. RESULTS: Among a total of 8,328 Enterobacterales, 2,241 Pseudomonas aeruginosa, and 586 Acinetobacter calcoaceticus-baumannii complex (ACB) clinical isolates from the United States, 50 Enterobacterales (0.6%), 36 P. aeruginosa (1.6%) and 114 ACB (19.5%) isolates showed a DTR phenotype, respectively. CFDC demonstrated its potent in vitro activity against these DTR isolates with MIC(90) of ≤4 μg/mL with a susceptibility rate of ≥92% except for DTR ACB based on FDA breakpoint (75.4%). In contrast, MIC(90)s of β-lactam/β-lactamase inhibitor combination drugs showed lower activity (Table). CONCLUSION: Cefiderocol demonstrated potent in vitro activity against DTR isolates of Enterobacterales, P. aeruginosa and ACB, indicating cefiderocol has high potential for treating infections caused by these difficult-to-treat strains. DISCLOSURES: Yoshinori Yamano, PhD, Shionogi: Employee Miki Takemura, n/a, Shionogi: Employee Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Christine M. Slover, PharmD, Shionogi: Employee Christopher M. Longshaw, PhD, Shionogi: Employee Roger Echols, MD, Shionogi: Advisor/Consultant Roger Echols, MD, Shionogi: Advisor/Consultant Roger Echols, MD, Shionogi: Advisor/Consultant. Oxford University Press 2022-12-15 /pmc/articles/PMC9752713/ http://dx.doi.org/10.1093/ofid/ofac492.1345 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstracts
Yamano, Yoshinori
Takemura, Miki
Shortridge, Dee
Slover, Christine M
Longshaw, Christopher M
Echols, Roger
Echols, Roger
Echols, Roger
1715. In Vitro Antibacterial Activity of Cefiderocol against Difficult-to-treat Resistant (DTR) Gram-negative Pathogens in United States from SENTRY Antimicrobial Surveillance Program in 2020/2021
title 1715. In Vitro Antibacterial Activity of Cefiderocol against Difficult-to-treat Resistant (DTR) Gram-negative Pathogens in United States from SENTRY Antimicrobial Surveillance Program in 2020/2021
title_full 1715. In Vitro Antibacterial Activity of Cefiderocol against Difficult-to-treat Resistant (DTR) Gram-negative Pathogens in United States from SENTRY Antimicrobial Surveillance Program in 2020/2021
title_fullStr 1715. In Vitro Antibacterial Activity of Cefiderocol against Difficult-to-treat Resistant (DTR) Gram-negative Pathogens in United States from SENTRY Antimicrobial Surveillance Program in 2020/2021
title_full_unstemmed 1715. In Vitro Antibacterial Activity of Cefiderocol against Difficult-to-treat Resistant (DTR) Gram-negative Pathogens in United States from SENTRY Antimicrobial Surveillance Program in 2020/2021
title_short 1715. In Vitro Antibacterial Activity of Cefiderocol against Difficult-to-treat Resistant (DTR) Gram-negative Pathogens in United States from SENTRY Antimicrobial Surveillance Program in 2020/2021
title_sort 1715. in vitro antibacterial activity of cefiderocol against difficult-to-treat resistant (dtr) gram-negative pathogens in united states from sentry antimicrobial surveillance program in 2020/2021
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9752713/
http://dx.doi.org/10.1093/ofid/ofac492.1345
work_keys_str_mv AT yamanoyoshinori 1715invitroantibacterialactivityofcefiderocolagainstdifficulttotreatresistantdtrgramnegativepathogensinunitedstatesfromsentryantimicrobialsurveillanceprogramin20202021
AT takemuramiki 1715invitroantibacterialactivityofcefiderocolagainstdifficulttotreatresistantdtrgramnegativepathogensinunitedstatesfromsentryantimicrobialsurveillanceprogramin20202021
AT shortridgedee 1715invitroantibacterialactivityofcefiderocolagainstdifficulttotreatresistantdtrgramnegativepathogensinunitedstatesfromsentryantimicrobialsurveillanceprogramin20202021
AT sloverchristinem 1715invitroantibacterialactivityofcefiderocolagainstdifficulttotreatresistantdtrgramnegativepathogensinunitedstatesfromsentryantimicrobialsurveillanceprogramin20202021
AT longshawchristopherm 1715invitroantibacterialactivityofcefiderocolagainstdifficulttotreatresistantdtrgramnegativepathogensinunitedstatesfromsentryantimicrobialsurveillanceprogramin20202021
AT echolsroger 1715invitroantibacterialactivityofcefiderocolagainstdifficulttotreatresistantdtrgramnegativepathogensinunitedstatesfromsentryantimicrobialsurveillanceprogramin20202021
AT echolsroger 1715invitroantibacterialactivityofcefiderocolagainstdifficulttotreatresistantdtrgramnegativepathogensinunitedstatesfromsentryantimicrobialsurveillanceprogramin20202021
AT echolsroger 1715invitroantibacterialactivityofcefiderocolagainstdifficulttotreatresistantdtrgramnegativepathogensinunitedstatesfromsentryantimicrobialsurveillanceprogramin20202021