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Cefiderocol Treatment for Patients with Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program
Cefiderocol is an option for infections caused by multidrug-resistant Pseudomonas aeruginosa, but its in vitro activity against these isolates and its clinical effectiveness for isolates with MICs of >1 μg/mL is unclear. We investigated the in vitro activity of cefiderocol against P. aeruginosa i...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353454/ https://www.ncbi.nlm.nih.gov/pubmed/37347188 http://dx.doi.org/10.1128/aac.00194-23 |
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author | Satlin, Michael J. Simner, Patricia J. Slover, Christine M. Yamano, Yoshinori Nagata, Tsutae D. Portsmouth, Simon |
author_facet | Satlin, Michael J. Simner, Patricia J. Slover, Christine M. Yamano, Yoshinori Nagata, Tsutae D. Portsmouth, Simon |
author_sort | Satlin, Michael J. |
collection | PubMed |
description | Cefiderocol is an option for infections caused by multidrug-resistant Pseudomonas aeruginosa, but its in vitro activity against these isolates and its clinical effectiveness for isolates with MICs of >1 μg/mL is unclear. We investigated the in vitro activity of cefiderocol against P. aeruginosa isolates collected from patients treated with cefiderocol through the compassionate use program and assessed physician-reported clinical response and 28-day all-cause mortality by cefiderocol MIC values. P. aeruginosa isolates underwent susceptibility testing to cefiderocol and comparator agents by using reference broth microdilution. U.S. Food and Drug Administration (FDA; susceptible, ≤1 μg/mL) and Clinical and Laboratory Standards Institute (CLSI; susceptible, ≤4 μg/mL) cefiderocol breakpoints were applied. Additionally, molecular characterization of β-lactamase genes was performed. Clinical response and vital status were reported by treating physicians. Forty-six patients with P. aeruginosa infections were evaluated. Twenty-nine (63%) and 42 (91%) isolates were susceptible to cefiderocol using FDA and CLSI breakpoints, respectively. Thirty-seven (80%) and 32 (70%) isolates were not susceptible to ceftolozane-tazobactam and ceftazidime-avibactam, respectively. The clinical response rate was 69% (20/29) with a cefiderocol MIC of ≤1 μg/mL, 69% (9/13) with a cefiderocol MIC of 2 to 4 μg/mL, and 100% (4/4) with an MIC of ≥8 μg/mL, while day 28 all-cause mortality rates were 23% (6/26; MIC ≤ 1 μg/mL), 33% (4/12; MIC, 2 to 4 μg/mL), and 0% (0/4; MIC ≥8 μg/mL), respectively. Cefiderocol was active in vitro against most P. aeruginosa isolated from patients with limited or no alternative therapies. Patients with cefiderocol MICs of 2 to 4 μg/mL did not have significantly worse outcomes than those with MICs of ≤1 μg/mL. |
format | Online Article Text |
id | pubmed-10353454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-103534542023-07-19 Cefiderocol Treatment for Patients with Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program Satlin, Michael J. Simner, Patricia J. Slover, Christine M. Yamano, Yoshinori Nagata, Tsutae D. Portsmouth, Simon Antimicrob Agents Chemother Clinical Therapeutics Cefiderocol is an option for infections caused by multidrug-resistant Pseudomonas aeruginosa, but its in vitro activity against these isolates and its clinical effectiveness for isolates with MICs of >1 μg/mL is unclear. We investigated the in vitro activity of cefiderocol against P. aeruginosa isolates collected from patients treated with cefiderocol through the compassionate use program and assessed physician-reported clinical response and 28-day all-cause mortality by cefiderocol MIC values. P. aeruginosa isolates underwent susceptibility testing to cefiderocol and comparator agents by using reference broth microdilution. U.S. Food and Drug Administration (FDA; susceptible, ≤1 μg/mL) and Clinical and Laboratory Standards Institute (CLSI; susceptible, ≤4 μg/mL) cefiderocol breakpoints were applied. Additionally, molecular characterization of β-lactamase genes was performed. Clinical response and vital status were reported by treating physicians. Forty-six patients with P. aeruginosa infections were evaluated. Twenty-nine (63%) and 42 (91%) isolates were susceptible to cefiderocol using FDA and CLSI breakpoints, respectively. Thirty-seven (80%) and 32 (70%) isolates were not susceptible to ceftolozane-tazobactam and ceftazidime-avibactam, respectively. The clinical response rate was 69% (20/29) with a cefiderocol MIC of ≤1 μg/mL, 69% (9/13) with a cefiderocol MIC of 2 to 4 μg/mL, and 100% (4/4) with an MIC of ≥8 μg/mL, while day 28 all-cause mortality rates were 23% (6/26; MIC ≤ 1 μg/mL), 33% (4/12; MIC, 2 to 4 μg/mL), and 0% (0/4; MIC ≥8 μg/mL), respectively. Cefiderocol was active in vitro against most P. aeruginosa isolated from patients with limited or no alternative therapies. Patients with cefiderocol MICs of 2 to 4 μg/mL did not have significantly worse outcomes than those with MICs of ≤1 μg/mL. American Society for Microbiology 2023-06-22 /pmc/articles/PMC10353454/ /pubmed/37347188 http://dx.doi.org/10.1128/aac.00194-23 Text en Copyright © 2023 Satlin et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Clinical Therapeutics Satlin, Michael J. Simner, Patricia J. Slover, Christine M. Yamano, Yoshinori Nagata, Tsutae D. Portsmouth, Simon Cefiderocol Treatment for Patients with Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program |
title | Cefiderocol Treatment for Patients with Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program |
title_full | Cefiderocol Treatment for Patients with Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program |
title_fullStr | Cefiderocol Treatment for Patients with Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program |
title_full_unstemmed | Cefiderocol Treatment for Patients with Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program |
title_short | Cefiderocol Treatment for Patients with Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program |
title_sort | cefiderocol treatment for patients with multidrug- and carbapenem-resistant pseudomonas aeruginosa infections in the compassionate use program |
topic | Clinical Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353454/ https://www.ncbi.nlm.nih.gov/pubmed/37347188 http://dx.doi.org/10.1128/aac.00194-23 |
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