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Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae

Carbapenem-resistant Enterobacteriaceae (CRE) is listed as an urgent threat by the World Health Organization because of the limited therapeutic options, rapid evolution of resistance mechanisms, and worldwide dissemination. Colistin is a common backbone agent among the “last-resort” antibiotics for...

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Autores principales: Chang, Ya-Ting, Yang, Tsung-Ying, Lu, Po-Liang, Lin, Shang-Yi, Wang, Liang-Chun, Wang, Sheng-Fan, Hsieh, Ya-Ju, Tseng, Sung-Pin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764370/
https://www.ncbi.nlm.nih.gov/pubmed/33322306
http://dx.doi.org/10.3390/microorganisms8121964
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author Chang, Ya-Ting
Yang, Tsung-Ying
Lu, Po-Liang
Lin, Shang-Yi
Wang, Liang-Chun
Wang, Sheng-Fan
Hsieh, Ya-Ju
Tseng, Sung-Pin
author_facet Chang, Ya-Ting
Yang, Tsung-Ying
Lu, Po-Liang
Lin, Shang-Yi
Wang, Liang-Chun
Wang, Sheng-Fan
Hsieh, Ya-Ju
Tseng, Sung-Pin
author_sort Chang, Ya-Ting
collection PubMed
description Carbapenem-resistant Enterobacteriaceae (CRE) is listed as an urgent threat by the World Health Organization because of the limited therapeutic options, rapid evolution of resistance mechanisms, and worldwide dissemination. Colistin is a common backbone agent among the “last-resort” antibiotics for CRE; however, its emerging resistance among CRE has taken the present dilemma to the next level. Azidothymidine (AZT), a thymidine analog used to treat human immunodeficiency virus/acquired immunodeficiency syndrome, has been known to possess antibacterial effects against Enterobacteriaceae. In this study, we investigated the combined effects of AZT and colistin in 40 clinical isolates of colistin-resistant, carbapenem-resistant K. pneumoniae (CCRKP). Eleven of the 40 isolates harbored Klebsiella pneumoniae carbapenemase. The in vitro checkerboard method and in vivo nematode killing assay both revealed synergistic activity between the two agents, with fractional inhibitory concentration indexes of ≤0.5 in every strain. Additionally, a significantly lower hazard ratio was observed for the nematodes treated with combination therapy (0.288; p < 0.0001) compared with either AZT or colistin treatment. Toxicity testing indicated potentially low toxicity of the combination therapy. Thus, the AZT–colistin combination could be a potentially favorable therapeutic option for treating CCRKP.
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spelling pubmed-77643702020-12-27 Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae Chang, Ya-Ting Yang, Tsung-Ying Lu, Po-Liang Lin, Shang-Yi Wang, Liang-Chun Wang, Sheng-Fan Hsieh, Ya-Ju Tseng, Sung-Pin Microorganisms Article Carbapenem-resistant Enterobacteriaceae (CRE) is listed as an urgent threat by the World Health Organization because of the limited therapeutic options, rapid evolution of resistance mechanisms, and worldwide dissemination. Colistin is a common backbone agent among the “last-resort” antibiotics for CRE; however, its emerging resistance among CRE has taken the present dilemma to the next level. Azidothymidine (AZT), a thymidine analog used to treat human immunodeficiency virus/acquired immunodeficiency syndrome, has been known to possess antibacterial effects against Enterobacteriaceae. In this study, we investigated the combined effects of AZT and colistin in 40 clinical isolates of colistin-resistant, carbapenem-resistant K. pneumoniae (CCRKP). Eleven of the 40 isolates harbored Klebsiella pneumoniae carbapenemase. The in vitro checkerboard method and in vivo nematode killing assay both revealed synergistic activity between the two agents, with fractional inhibitory concentration indexes of ≤0.5 in every strain. Additionally, a significantly lower hazard ratio was observed for the nematodes treated with combination therapy (0.288; p < 0.0001) compared with either AZT or colistin treatment. Toxicity testing indicated potentially low toxicity of the combination therapy. Thus, the AZT–colistin combination could be a potentially favorable therapeutic option for treating CCRKP. MDPI 2020-12-11 /pmc/articles/PMC7764370/ /pubmed/33322306 http://dx.doi.org/10.3390/microorganisms8121964 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Ya-Ting
Yang, Tsung-Ying
Lu, Po-Liang
Lin, Shang-Yi
Wang, Liang-Chun
Wang, Sheng-Fan
Hsieh, Ya-Ju
Tseng, Sung-Pin
Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae
title Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae
title_full Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae
title_fullStr Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae
title_full_unstemmed Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae
title_short Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae
title_sort combination of colistin and azidothymidine demonstrates synergistic activity against colistin-resistant, carbapenem-resistant klebsiella pneumoniae
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764370/
https://www.ncbi.nlm.nih.gov/pubmed/33322306
http://dx.doi.org/10.3390/microorganisms8121964
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