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701. Comparison of MIC Results for Gepotidacin by Agar Dilution and Broth Microdilution Methods

BACKGROUND: Gepotidacin (GSK2140944) is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in clinical development for the treatment of gonorrhea and uncomplicated UTI (acute cystitis). Gepotidacin selectively inhibits bacterial DNA gyrase and topoisomerase IV by a unique mechani...

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Autores principales: Arends, S J Ryan, Canino, Michele A, Roth, Brieanna M, Rhomberg, Paul R, Flamm, Robert K, Scangarella-Oman, Nicole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811067/
http://dx.doi.org/10.1093/ofid/ofz360.769
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author Arends, S J Ryan
Canino, Michele A
Roth, Brieanna M
Rhomberg, Paul R
Flamm, Robert K
Scangarella-Oman, Nicole
author_facet Arends, S J Ryan
Canino, Michele A
Roth, Brieanna M
Rhomberg, Paul R
Flamm, Robert K
Scangarella-Oman, Nicole
author_sort Arends, S J Ryan
collection PubMed
description BACKGROUND: Gepotidacin (GSK2140944) is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in clinical development for the treatment of gonorrhea and uncomplicated UTI (acute cystitis). Gepotidacin selectively inhibits bacterial DNA gyrase and topoisomerase IV by a unique mechanism not utilized by any currently approved therapeutic agent and demonstrates in vitro activity against most target pathogens resistant to established antibacterials, including fluoroquinolones. This study tested the equivalency of minimal inhibitory concentrations (MICs) obtained by 2 reference susceptibility testing methods, agar dilution (AD) and broth microdilution (BMD), for gepotidacin against Gram-positive and Gram-negative organisms. METHODS: Susceptibility testing for both methods was performed on a total of 733 clinical isolates recovered largely in 2016 from over 120 medical centers worldwide. For N. gonorrhoeae, only the AD method is recommended by CLSI, therefore BMD was performed using Fastidious Broth for comparison purposes. Essential agreement (EA) based on evaluable results was calculated as the number of isolates with MICs within one 2-fold dilution of the reference method divided by the total number of results. Equivalency was defined using the 95% criteria from the FDA’s class II controls document. RESULTS: The EA observed for gepotidacin with these 2 methods was 85.8% overall and 98.3% when H. influenzae and N. gonorrhoeae isolates were excluded. Slightly higher gepotidacin MICs were observed when tested by BMD for each of these species/groups; this trend was especially prominent for E. coli and S. pyogenes. Gepotidacin tested against H. influenzae (73.1%) or N. gonorrhoeae (28.6%) species had much lower EAs. CONCLUSION: Equivalency (EA >95%) was established between AD and BMD methods for determining gepotidacin susceptibility results against Staphylococcus spp., Streptococcus spp. and E. coli. However, for N. gonorrhoeae and H. influenzae, equivalency between the 2 methods was not established; therefore, future antimicrobial susceptibility testing for gepotidacin against these organisms should adhere to the methods for which quality control ranges and breakpoints are approved. [Image: see text] DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68110672019-10-28 701. Comparison of MIC Results for Gepotidacin by Agar Dilution and Broth Microdilution Methods Arends, S J Ryan Canino, Michele A Roth, Brieanna M Rhomberg, Paul R Flamm, Robert K Scangarella-Oman, Nicole Open Forum Infect Dis Abstracts BACKGROUND: Gepotidacin (GSK2140944) is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in clinical development for the treatment of gonorrhea and uncomplicated UTI (acute cystitis). Gepotidacin selectively inhibits bacterial DNA gyrase and topoisomerase IV by a unique mechanism not utilized by any currently approved therapeutic agent and demonstrates in vitro activity against most target pathogens resistant to established antibacterials, including fluoroquinolones. This study tested the equivalency of minimal inhibitory concentrations (MICs) obtained by 2 reference susceptibility testing methods, agar dilution (AD) and broth microdilution (BMD), for gepotidacin against Gram-positive and Gram-negative organisms. METHODS: Susceptibility testing for both methods was performed on a total of 733 clinical isolates recovered largely in 2016 from over 120 medical centers worldwide. For N. gonorrhoeae, only the AD method is recommended by CLSI, therefore BMD was performed using Fastidious Broth for comparison purposes. Essential agreement (EA) based on evaluable results was calculated as the number of isolates with MICs within one 2-fold dilution of the reference method divided by the total number of results. Equivalency was defined using the 95% criteria from the FDA’s class II controls document. RESULTS: The EA observed for gepotidacin with these 2 methods was 85.8% overall and 98.3% when H. influenzae and N. gonorrhoeae isolates were excluded. Slightly higher gepotidacin MICs were observed when tested by BMD for each of these species/groups; this trend was especially prominent for E. coli and S. pyogenes. Gepotidacin tested against H. influenzae (73.1%) or N. gonorrhoeae (28.6%) species had much lower EAs. CONCLUSION: Equivalency (EA >95%) was established between AD and BMD methods for determining gepotidacin susceptibility results against Staphylococcus spp., Streptococcus spp. and E. coli. However, for N. gonorrhoeae and H. influenzae, equivalency between the 2 methods was not established; therefore, future antimicrobial susceptibility testing for gepotidacin against these organisms should adhere to the methods for which quality control ranges and breakpoints are approved. [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6811067/ http://dx.doi.org/10.1093/ofid/ofz360.769 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
Arends, S J Ryan
Canino, Michele A
Roth, Brieanna M
Rhomberg, Paul R
Flamm, Robert K
Scangarella-Oman, Nicole
701. Comparison of MIC Results for Gepotidacin by Agar Dilution and Broth Microdilution Methods
title 701. Comparison of MIC Results for Gepotidacin by Agar Dilution and Broth Microdilution Methods
title_full 701. Comparison of MIC Results for Gepotidacin by Agar Dilution and Broth Microdilution Methods
title_fullStr 701. Comparison of MIC Results for Gepotidacin by Agar Dilution and Broth Microdilution Methods
title_full_unstemmed 701. Comparison of MIC Results for Gepotidacin by Agar Dilution and Broth Microdilution Methods
title_short 701. Comparison of MIC Results for Gepotidacin by Agar Dilution and Broth Microdilution Methods
title_sort 701. comparison of mic results for gepotidacin by agar dilution and broth microdilution methods
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811067/
http://dx.doi.org/10.1093/ofid/ofz360.769
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