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Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates

Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially Acinetobacter baumannii. Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI),...

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Autores principales: Cedano, Jose, Baez, Michelle, Pasteran, Fernando, Montaña, Sabrina Daiana, Ra, Grace, Fua, Venjaminne, Corso, Alejandra, Tolmasky, Marcelo E., Bonomo, Robert A., Ramírez, María Soledad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309244/
https://www.ncbi.nlm.nih.gov/pubmed/35899052
http://dx.doi.org/10.3389/fcimb.2022.918868
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author Cedano, Jose
Baez, Michelle
Pasteran, Fernando
Montaña, Sabrina Daiana
Ra, Grace
Fua, Venjaminne
Corso, Alejandra
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
author_facet Cedano, Jose
Baez, Michelle
Pasteran, Fernando
Montaña, Sabrina Daiana
Ra, Grace
Fua, Venjaminne
Corso, Alejandra
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
author_sort Cedano, Jose
collection PubMed
description Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially Acinetobacter baumannii. Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI), when combined with sulbactam successfully restore sulbactam susceptibility against certain carbapenem-resistant A. baumannii (CRAB) isolates. In the present study, we tested zidebactam, a novel DBO with an additional mechanism of action, in combination with sulbactam against CRAB isolates, including strains that exhibited resistance against sulbactam/avibactam combination. A panel of 43 geographically and genetically distinct CRAB isolates recovered from different hospitals and containing different mechanisms of resistance were included in the present study. We also tested three reference strains (AB0057, AB5075, and AYE). Minimum inhibitory concentrations (MICs) for sulbactam (range 0.12–512 mg/l) and sulbactam plus 4 mg/l zidebactam were performed using microdilution according to CLSI Standards. A decrease ≥2 dilutions in sulbactam MICs was observed in 84% of the isolates when tested in combination with zidebactam. The sulbactam/zidebactam combination was able to restore sulbactam susceptibility in 91% of the isolates, including isolates that were resistant to sulbactam/avibactam combination. These data encouraged us to further explore sulbactam/zidebactam in other experimental models especially against CRAB isolates resistant to other DBOs.
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spelling pubmed-93092442022-07-26 Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates Cedano, Jose Baez, Michelle Pasteran, Fernando Montaña, Sabrina Daiana Ra, Grace Fua, Venjaminne Corso, Alejandra Tolmasky, Marcelo E. Bonomo, Robert A. Ramírez, María Soledad Front Cell Infect Microbiol Cellular and Infection Microbiology Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially Acinetobacter baumannii. Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI), when combined with sulbactam successfully restore sulbactam susceptibility against certain carbapenem-resistant A. baumannii (CRAB) isolates. In the present study, we tested zidebactam, a novel DBO with an additional mechanism of action, in combination with sulbactam against CRAB isolates, including strains that exhibited resistance against sulbactam/avibactam combination. A panel of 43 geographically and genetically distinct CRAB isolates recovered from different hospitals and containing different mechanisms of resistance were included in the present study. We also tested three reference strains (AB0057, AB5075, and AYE). Minimum inhibitory concentrations (MICs) for sulbactam (range 0.12–512 mg/l) and sulbactam plus 4 mg/l zidebactam were performed using microdilution according to CLSI Standards. A decrease ≥2 dilutions in sulbactam MICs was observed in 84% of the isolates when tested in combination with zidebactam. The sulbactam/zidebactam combination was able to restore sulbactam susceptibility in 91% of the isolates, including isolates that were resistant to sulbactam/avibactam combination. These data encouraged us to further explore sulbactam/zidebactam in other experimental models especially against CRAB isolates resistant to other DBOs. Frontiers Media S.A. 2022-07-08 /pmc/articles/PMC9309244/ /pubmed/35899052 http://dx.doi.org/10.3389/fcimb.2022.918868 Text en Copyright © 2022 Cedano, Baez, Pasteran, Montaña, Ra, Fua, Corso, Tolmasky, Bonomo and Ramírez https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Cedano, Jose
Baez, Michelle
Pasteran, Fernando
Montaña, Sabrina Daiana
Ra, Grace
Fua, Venjaminne
Corso, Alejandra
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title_full Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title_fullStr Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title_full_unstemmed Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title_short Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title_sort zidebactam restores sulbactam susceptibility against carbapenem-resistant acinetobacter baumannii isolates
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309244/
https://www.ncbi.nlm.nih.gov/pubmed/35899052
http://dx.doi.org/10.3389/fcimb.2022.918868
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