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710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)

BACKGROUND: Eravacycline (ERV) is a recently-approved, fully synthetic fluorocycline agent that demonstrates broad in vitro activity against multidrug-resistant pathogens. We sought to compare the activity of ERV with minocycline (MIN) and tigecycline (TGC) against diverse CRE clinical isolates, and...

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Autores principales: Jones, Chelsea E, Kline, Ellen G, Nguyen, Minh-Hong, Clancy, Cornelius J, Shields, Ryan K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811212/
http://dx.doi.org/10.1093/ofid/ofz360.778
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author Jones, Chelsea E
Kline, Ellen G
Nguyen, Minh-Hong
Clancy, Cornelius J
Shields, Ryan K
author_facet Jones, Chelsea E
Kline, Ellen G
Nguyen, Minh-Hong
Clancy, Cornelius J
Shields, Ryan K
author_sort Jones, Chelsea E
collection PubMed
description BACKGROUND: Eravacycline (ERV) is a recently-approved, fully synthetic fluorocycline agent that demonstrates broad in vitro activity against multidrug-resistant pathogens. We sought to compare the activity of ERV with minocycline (MIN) and tigecycline (TGC) against diverse CRE clinical isolates, and to evaluate the performance of commercially-available susceptibility testing methods. METHODS: ERV, MIN, and TGC minimum inhibitory concentrations (MICs) were determined in triplicate by broth microdilution against previously characterized CRE isolates. ERV susceptibility was also measured by disk diffusion (20 µg disk; Mast Group) and MIC test strips (MTS; Liofilchem) according to manufacturer instructions. RESULTS: 148 CRE were tested, including 92 K. pneumoniae, 32 Enterobacter spp, 11 E. coli, 5 C. freundii, 4 K. oxytoca, and 4 S. marcescens. 72% of isolates harbored bla(KPC), which encoded KPC-2 (n = 33), KPC-3 (n = 48), and other KPC variants (n = 22). 77% and 19% of isolates were resistant to meropenem and ceftazidime–avibactam, respectively. By BMD, the ERV, MIN, and TGC MIC range, MIC50 and MIC90 for shown in the Table. ERV MICs were ≥2-fold lower than MIN and TGC against 99% and 43% of isolates, respectively. ERV MICs did not vary by species or KPC-subtype. ERV MICs determined by BMD and MTS were well-correlated showing 89% essential agreement (MIC within one 2-fold dilution; Figure). The rate of categorical agreement (CA) was 73%. By comparison, the CA rate between BMD and disk diffusion was 78%. By both MTS and disk diffusion methods, susceptibility results clustered on either side of the susceptibility breakpoint. 50% of disk diffusion zones clustered between 14 and 16 millimeters (mm), which is 1 mm on either side of the susceptibility breakpoint (≥15 mm). CONCLUSION: This study confirms the in vitro activity of ERV against CRE clinical isolates, which is comparable to TGC. ERV MTS demonstrated high rates of EA, but lower rates of CA. Clinicians should be aware of the nuances of ERV susceptibility testing and recognize that the modal distribution of ERV MICs against CRE lies on either side of the susceptibility breakpoint. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68112122019-10-29 710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE) Jones, Chelsea E Kline, Ellen G Nguyen, Minh-Hong Clancy, Cornelius J Shields, Ryan K Open Forum Infect Dis Abstracts BACKGROUND: Eravacycline (ERV) is a recently-approved, fully synthetic fluorocycline agent that demonstrates broad in vitro activity against multidrug-resistant pathogens. We sought to compare the activity of ERV with minocycline (MIN) and tigecycline (TGC) against diverse CRE clinical isolates, and to evaluate the performance of commercially-available susceptibility testing methods. METHODS: ERV, MIN, and TGC minimum inhibitory concentrations (MICs) were determined in triplicate by broth microdilution against previously characterized CRE isolates. ERV susceptibility was also measured by disk diffusion (20 µg disk; Mast Group) and MIC test strips (MTS; Liofilchem) according to manufacturer instructions. RESULTS: 148 CRE were tested, including 92 K. pneumoniae, 32 Enterobacter spp, 11 E. coli, 5 C. freundii, 4 K. oxytoca, and 4 S. marcescens. 72% of isolates harbored bla(KPC), which encoded KPC-2 (n = 33), KPC-3 (n = 48), and other KPC variants (n = 22). 77% and 19% of isolates were resistant to meropenem and ceftazidime–avibactam, respectively. By BMD, the ERV, MIN, and TGC MIC range, MIC50 and MIC90 for shown in the Table. ERV MICs were ≥2-fold lower than MIN and TGC against 99% and 43% of isolates, respectively. ERV MICs did not vary by species or KPC-subtype. ERV MICs determined by BMD and MTS were well-correlated showing 89% essential agreement (MIC within one 2-fold dilution; Figure). The rate of categorical agreement (CA) was 73%. By comparison, the CA rate between BMD and disk diffusion was 78%. By both MTS and disk diffusion methods, susceptibility results clustered on either side of the susceptibility breakpoint. 50% of disk diffusion zones clustered between 14 and 16 millimeters (mm), which is 1 mm on either side of the susceptibility breakpoint (≥15 mm). CONCLUSION: This study confirms the in vitro activity of ERV against CRE clinical isolates, which is comparable to TGC. ERV MTS demonstrated high rates of EA, but lower rates of CA. Clinicians should be aware of the nuances of ERV susceptibility testing and recognize that the modal distribution of ERV MICs against CRE lies on either side of the susceptibility breakpoint. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6811212/ http://dx.doi.org/10.1093/ofid/ofz360.778 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
Jones, Chelsea E
Kline, Ellen G
Nguyen, Minh-Hong
Clancy, Cornelius J
Shields, Ryan K
710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)
title 710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)
title_full 710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)
title_fullStr 710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)
title_full_unstemmed 710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)
title_short 710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)
title_sort 710. in vitro activity and performance of available susceptibility testing methods for eravacycline against carbapenem-resistant enterobacteriaceae (cre)
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811212/
http://dx.doi.org/10.1093/ofid/ofz360.778
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