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698. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Multidrug-Resistant Gram-Negative Bacilli
BACKGROUND: Multidrug-resistant Gram-negative bacilli (MDRGNB) are emerging as a challenging cause of hospital-acquired infections and represent a critical need for innovative antibacterial development. New oxopyrazole agents targeting penicillin-binding proteins (PBPs) based on a non-β-lactam core...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811137/ http://dx.doi.org/10.1093/ofid/ofz360.766 |
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author | Goldberg, Joel Bethel, Christopher Hujer, Andrea M Hujer, Kristine Marshall, Steven Papp-Wallace, Krisztina M Perez, Federico Spencer, Elizabeth Hoyer, Denton Plummer, Mark Bonomo, Robert A |
author_facet | Goldberg, Joel Bethel, Christopher Hujer, Andrea M Hujer, Kristine Marshall, Steven Papp-Wallace, Krisztina M Perez, Federico Spencer, Elizabeth Hoyer, Denton Plummer, Mark Bonomo, Robert A |
author_sort | Goldberg, Joel |
collection | PubMed |
description | BACKGROUND: Multidrug-resistant Gram-negative bacilli (MDRGNB) are emerging as a challenging cause of hospital-acquired infections and represent a critical need for innovative antibacterial development. New oxopyrazole agents targeting penicillin-binding proteins (PBPs) based on a non-β-lactam core and incorporating a siderophore moiety (Figure 1) which facilitates transport to the periplasm are being developed that show promise against Gram-negative organisms including multidrug-resistant strains of E. coli, K. pneumoniae and P. aeruginosa. METHODS: YU253434, an example of this new class of antibacterials, was investigated in vitro. Minimum inhibitory concentrations (MICs) were determined by broth microdilution against a representative panel comprising 15 strains each of E. coli, K. pneumoniae and P. aeruginosa, which contain extended-spectrum β-lactamase (ESBL) and/or carbapenemases genes.All studies were performed according to current Clinical & Laboratory Standards Institute (CLSI) guidelines using iron-depleted media. Ceftazidime breakpoints were arbitrability chosen as a reference for YU253434 (susceptibilities ≤4 μg/mL for Enterobacteriaceae and ≤8 μg/mL for P. aeruginosa). RESULTS: MIC testing (Figures 2–4) against E. coli showed 11 strains were YU253434 susceptible (compared with 6 for ceftazidime, and 3 for imipenem); against K. pneumoniae 13 strains were YU253434 susceptible (compared with 2 for ceftazidime and 6 for imipenem); against P. aeruginosa 10 strains were YU253434 susceptible (compared with 0 for both ceftazidime and imipenem). There appeared to be no correlation between YU253434 resistance and the presence of specific lactamase genes. CONCLUSION: YU253434, a new generation oxopyrazole antibiotic, demonstrated promising in vitro potency against a panel of E. coli, K. pneumonia, and P. aeruginosa strains which contain ESBL and/or carbapenemases genes. [Image: see text] [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures. |
format | Online Article Text |
id | pubmed-6811137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68111372019-10-28 698. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Multidrug-Resistant Gram-Negative Bacilli Goldberg, Joel Bethel, Christopher Hujer, Andrea M Hujer, Kristine Marshall, Steven Papp-Wallace, Krisztina M Perez, Federico Spencer, Elizabeth Hoyer, Denton Plummer, Mark Bonomo, Robert A Open Forum Infect Dis Abstracts BACKGROUND: Multidrug-resistant Gram-negative bacilli (MDRGNB) are emerging as a challenging cause of hospital-acquired infections and represent a critical need for innovative antibacterial development. New oxopyrazole agents targeting penicillin-binding proteins (PBPs) based on a non-β-lactam core and incorporating a siderophore moiety (Figure 1) which facilitates transport to the periplasm are being developed that show promise against Gram-negative organisms including multidrug-resistant strains of E. coli, K. pneumoniae and P. aeruginosa. METHODS: YU253434, an example of this new class of antibacterials, was investigated in vitro. Minimum inhibitory concentrations (MICs) were determined by broth microdilution against a representative panel comprising 15 strains each of E. coli, K. pneumoniae and P. aeruginosa, which contain extended-spectrum β-lactamase (ESBL) and/or carbapenemases genes.All studies were performed according to current Clinical & Laboratory Standards Institute (CLSI) guidelines using iron-depleted media. Ceftazidime breakpoints were arbitrability chosen as a reference for YU253434 (susceptibilities ≤4 μg/mL for Enterobacteriaceae and ≤8 μg/mL for P. aeruginosa). RESULTS: MIC testing (Figures 2–4) against E. coli showed 11 strains were YU253434 susceptible (compared with 6 for ceftazidime, and 3 for imipenem); against K. pneumoniae 13 strains were YU253434 susceptible (compared with 2 for ceftazidime and 6 for imipenem); against P. aeruginosa 10 strains were YU253434 susceptible (compared with 0 for both ceftazidime and imipenem). There appeared to be no correlation between YU253434 resistance and the presence of specific lactamase genes. CONCLUSION: YU253434, a new generation oxopyrazole antibiotic, demonstrated promising in vitro potency against a panel of E. coli, K. pneumonia, and P. aeruginosa strains which contain ESBL and/or carbapenemases genes. [Image: see text] [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6811137/ http://dx.doi.org/10.1093/ofid/ofz360.766 Text en © The Author(s) 2019. 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 Goldberg, Joel Bethel, Christopher Hujer, Andrea M Hujer, Kristine Marshall, Steven Papp-Wallace, Krisztina M Perez, Federico Spencer, Elizabeth Hoyer, Denton Plummer, Mark Bonomo, Robert A 698. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Multidrug-Resistant Gram-Negative Bacilli |
title | 698. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Multidrug-Resistant Gram-Negative Bacilli |
title_full | 698. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Multidrug-Resistant Gram-Negative Bacilli |
title_fullStr | 698. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Multidrug-Resistant Gram-Negative Bacilli |
title_full_unstemmed | 698. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Multidrug-Resistant Gram-Negative Bacilli |
title_short | 698. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Multidrug-Resistant Gram-Negative Bacilli |
title_sort | 698. in vitro activity of a new generation oxopyrazole antibiotic against multidrug-resistant gram-negative bacilli |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811137/ http://dx.doi.org/10.1093/ofid/ofz360.766 |
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