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786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?

BACKGROUND: Mycobacterium abscessus harbors a β-lactamase enzyme, Bla(Mab), able to hydrolyze penicillins, most cephalosporins and carbapenems. As of today, management of M. abscessus with β-lactams does not include combination of β-lactamase inhibitors. The potential benefit of combinations of seve...

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Autores principales: Dousa, Khalid M, Kreiswirth, Barry N, Kurz, Sebastian, Bonomo, Robert A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254396/
http://dx.doi.org/10.1093/ofid/ofy210.793
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author Dousa, Khalid M
Kreiswirth, Barry N
Kurz, Sebastian
Bonomo, Robert A
author_facet Dousa, Khalid M
Kreiswirth, Barry N
Kurz, Sebastian
Bonomo, Robert A
author_sort Dousa, Khalid M
collection PubMed
description BACKGROUND: Mycobacterium abscessus harbors a β-lactamase enzyme, Bla(Mab), able to hydrolyze penicillins, most cephalosporins and carbapenems. As of today, management of M. abscessus with β-lactams does not include combination of β-lactamase inhibitors. The potential benefit of combinations of several β-lactams with new diazabicyclooctane (DBO) inhibitors, such as relebactam and avibactam, has not been well studied. Based upon the ability to inhibit BlaMab by highly potent DBO inhibitors, our goal herein was to investigate the efficacy of a novel combination, ceftaroline (CEF) and avibactam (AVI), to restore susceptibility to β-lactam antibiotics and inhibit growth. METHODS: Minimum inhibitory concentrations (MICs) of CEF with or without AVI were examined using the microdilution method. RESULTS: MIC(50) and MIC(90) of CEF is 8 mg/L; in the presence of 4 μg/mL of AVI, the MICs of CEF decreased to ≤4 mg/L in 31 of 35 cases (table). CONCLUSION: Our results add to the growing evidence of using β-lactams as agents effective against Mycobacterial infections. Inhibition of the hydrolytic activity of (BlaMab) using DBOs such as AVI suggest that this combination should be evaluated in animal and clinical models. DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-62543962018-11-28 786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection? Dousa, Khalid M Kreiswirth, Barry N Kurz, Sebastian Bonomo, Robert A Open Forum Infect Dis Abstracts BACKGROUND: Mycobacterium abscessus harbors a β-lactamase enzyme, Bla(Mab), able to hydrolyze penicillins, most cephalosporins and carbapenems. As of today, management of M. abscessus with β-lactams does not include combination of β-lactamase inhibitors. The potential benefit of combinations of several β-lactams with new diazabicyclooctane (DBO) inhibitors, such as relebactam and avibactam, has not been well studied. Based upon the ability to inhibit BlaMab by highly potent DBO inhibitors, our goal herein was to investigate the efficacy of a novel combination, ceftaroline (CEF) and avibactam (AVI), to restore susceptibility to β-lactam antibiotics and inhibit growth. METHODS: Minimum inhibitory concentrations (MICs) of CEF with or without AVI were examined using the microdilution method. RESULTS: MIC(50) and MIC(90) of CEF is 8 mg/L; in the presence of 4 μg/mL of AVI, the MICs of CEF decreased to ≤4 mg/L in 31 of 35 cases (table). CONCLUSION: Our results add to the growing evidence of using β-lactams as agents effective against Mycobacterial infections. Inhibition of the hydrolytic activity of (BlaMab) using DBOs such as AVI suggest that this combination should be evaluated in animal and clinical models. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2018-11-26 /pmc/articles/PMC6254396/ http://dx.doi.org/10.1093/ofid/ofy210.793 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Dousa, Khalid M
Kreiswirth, Barry N
Kurz, Sebastian
Bonomo, Robert A
786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?
title 786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?
title_full 786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?
title_fullStr 786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?
title_full_unstemmed 786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?
title_short 786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?
title_sort 786. ceftaroline and avibactam? is this a potential combination for mycobacterium abscessus infection?
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254396/
http://dx.doi.org/10.1093/ofid/ofy210.793
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