Cargando…

2149. In vitro Activity of Aztreonam-avibactam and Comparator Agents Against Carbapenem-Resistant Enterobacterales With and Without Carbapenemases, ATLAS Global Surveillance Program, 2017–2021

BACKGROUND: The investigational β-lactam/non-β-lactam β-lactamase inhibitor combination aztreonam-avibactam (ATM-AVI) is active in vitro against CRE isolates, including MBL-producers, as well as those co-producing serine β-lactamases of Class A, C, and some class D types. This study evaluated the in...

Descripción completa

Detalles Bibliográficos
Autores principales: Wise, Mark G, Arhin, Francis, Sahm, Daniel F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10677420/
http://dx.doi.org/10.1093/ofid/ofad500.1772
_version_ 1785150125986807808
author Wise, Mark G
Arhin, Francis
Sahm, Daniel F
author_facet Wise, Mark G
Arhin, Francis
Sahm, Daniel F
author_sort Wise, Mark G
collection PubMed
description BACKGROUND: The investigational β-lactam/non-β-lactam β-lactamase inhibitor combination aztreonam-avibactam (ATM-AVI) is active in vitro against CRE isolates, including MBL-producers, as well as those co-producing serine β-lactamases of Class A, C, and some class D types. This study evaluated the in vitro activity of ATM-AVI and comparators against carbapenemase- and non-carbapenemase-producing CRE collected globally from 2017−2021 as part of the ATLAS surveillance program. METHODS: 85,990 non-duplicate, clinically relevant Enterobacterales isolates were collected from 258 medical centers located in 56 countries worldwide (excluding N. America and China). Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2023 breakpoints. ATM-AVI was tested at a fixed concentration of 4 mg/L avibactam. A tentative ATM-AVI pharmacokinetic/pharmacodynamic (PK/PD) susceptible MIC breakpoint of ≤ 8 mg/L was applied for comparison purposes. Organisms with meropenem MIC >1 mg/L and Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with aztreonam or ceftazidime MIC >1 mg/L were screened for β-lactamase genes by PCR and Sanger sequencing. RESULTS: In total, 5,473 isolates were identified as CRE based on resistance to meropenem. ATM-AVI demonstrated potent in vitro activity against the CRE, with 99.3% of isolates (MIC(90), 1 mg/L) inhibited at ≤8 mg/L (Table). ATM-AVI inhibited 99.5% of the carbapenemase-positive CRE, including 99.1% of the MBL-carriers (n=2,375) and 99.8% of serine-carbapenemase carriers (n=2,675) at ≤8 mg/L. Activity was somewhat reduced against the 441 CRE without detected carbapenemases as 96.3% (MIC(90), 4 mg/L) of the isolates were inhibited at ≤8 mg/L aztreonam-avibactam. Amikacin was the most active comparator, although < 50% of each subgroup was susceptible at the CLSI breakpoint. [Figure: see text] CONCLUSION: Based on MIC(90) values and the preliminary PK/PD breakpoint, ATM-AVI demonstrated potent in vitro activity against CRE, including MBL- and serine carbapenemase-carrying isolates. As limited therapeutic options presently exist for treating infections caused by CRE, further development of this agent appears warranted. DISCLOSURES: Mark G Wise, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation
format Online
Article
Text
id pubmed-10677420
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-106774202023-11-27 2149. In vitro Activity of Aztreonam-avibactam and Comparator Agents Against Carbapenem-Resistant Enterobacterales With and Without Carbapenemases, ATLAS Global Surveillance Program, 2017–2021 Wise, Mark G Arhin, Francis Sahm, Daniel F Open Forum Infect Dis Abstract BACKGROUND: The investigational β-lactam/non-β-lactam β-lactamase inhibitor combination aztreonam-avibactam (ATM-AVI) is active in vitro against CRE isolates, including MBL-producers, as well as those co-producing serine β-lactamases of Class A, C, and some class D types. This study evaluated the in vitro activity of ATM-AVI and comparators against carbapenemase- and non-carbapenemase-producing CRE collected globally from 2017−2021 as part of the ATLAS surveillance program. METHODS: 85,990 non-duplicate, clinically relevant Enterobacterales isolates were collected from 258 medical centers located in 56 countries worldwide (excluding N. America and China). Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2023 breakpoints. ATM-AVI was tested at a fixed concentration of 4 mg/L avibactam. A tentative ATM-AVI pharmacokinetic/pharmacodynamic (PK/PD) susceptible MIC breakpoint of ≤ 8 mg/L was applied for comparison purposes. Organisms with meropenem MIC >1 mg/L and Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with aztreonam or ceftazidime MIC >1 mg/L were screened for β-lactamase genes by PCR and Sanger sequencing. RESULTS: In total, 5,473 isolates were identified as CRE based on resistance to meropenem. ATM-AVI demonstrated potent in vitro activity against the CRE, with 99.3% of isolates (MIC(90), 1 mg/L) inhibited at ≤8 mg/L (Table). ATM-AVI inhibited 99.5% of the carbapenemase-positive CRE, including 99.1% of the MBL-carriers (n=2,375) and 99.8% of serine-carbapenemase carriers (n=2,675) at ≤8 mg/L. Activity was somewhat reduced against the 441 CRE without detected carbapenemases as 96.3% (MIC(90), 4 mg/L) of the isolates were inhibited at ≤8 mg/L aztreonam-avibactam. Amikacin was the most active comparator, although < 50% of each subgroup was susceptible at the CLSI breakpoint. [Figure: see text] CONCLUSION: Based on MIC(90) values and the preliminary PK/PD breakpoint, ATM-AVI demonstrated potent in vitro activity against CRE, including MBL- and serine carbapenemase-carrying isolates. As limited therapeutic options presently exist for treating infections caused by CRE, further development of this agent appears warranted. DISCLOSURES: Mark G Wise, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Oxford University Press 2023-11-27 /pmc/articles/PMC10677420/ http://dx.doi.org/10.1093/ofid/ofad500.1772 Text en © The Author(s) 2023. 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 Abstract
Wise, Mark G
Arhin, Francis
Sahm, Daniel F
2149. In vitro Activity of Aztreonam-avibactam and Comparator Agents Against Carbapenem-Resistant Enterobacterales With and Without Carbapenemases, ATLAS Global Surveillance Program, 2017–2021
title 2149. In vitro Activity of Aztreonam-avibactam and Comparator Agents Against Carbapenem-Resistant Enterobacterales With and Without Carbapenemases, ATLAS Global Surveillance Program, 2017–2021
title_full 2149. In vitro Activity of Aztreonam-avibactam and Comparator Agents Against Carbapenem-Resistant Enterobacterales With and Without Carbapenemases, ATLAS Global Surveillance Program, 2017–2021
title_fullStr 2149. In vitro Activity of Aztreonam-avibactam and Comparator Agents Against Carbapenem-Resistant Enterobacterales With and Without Carbapenemases, ATLAS Global Surveillance Program, 2017–2021
title_full_unstemmed 2149. In vitro Activity of Aztreonam-avibactam and Comparator Agents Against Carbapenem-Resistant Enterobacterales With and Without Carbapenemases, ATLAS Global Surveillance Program, 2017–2021
title_short 2149. In vitro Activity of Aztreonam-avibactam and Comparator Agents Against Carbapenem-Resistant Enterobacterales With and Without Carbapenemases, ATLAS Global Surveillance Program, 2017–2021
title_sort 2149. in vitro activity of aztreonam-avibactam and comparator agents against carbapenem-resistant enterobacterales with and without carbapenemases, atlas global surveillance program, 2017–2021
topic Abstract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10677420/
http://dx.doi.org/10.1093/ofid/ofad500.1772
work_keys_str_mv AT wisemarkg 2149invitroactivityofaztreonamavibactamandcomparatoragentsagainstcarbapenemresistantenterobacteraleswithandwithoutcarbapenemasesatlasglobalsurveillanceprogram20172021
AT arhinfrancis 2149invitroactivityofaztreonamavibactamandcomparatoragentsagainstcarbapenemresistantenterobacteraleswithandwithoutcarbapenemasesatlasglobalsurveillanceprogram20172021
AT sahmdanielf 2149invitroactivityofaztreonamavibactamandcomparatoragentsagainstcarbapenemresistantenterobacteraleswithandwithoutcarbapenemasesatlasglobalsurveillanceprogram20172021