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Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease

INTRODUCTION: Mycobacterium abscessus is an emerging pulmonary pathogen with limited treatment options. Nitric oxide (NO) demonstrates antibacterial activity against various bacterial species, including mycobacteria. In this study, we evaluated the effect of adjunctive inhaled NO therapy, using a no...

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Autores principales: Bogdanovski, Kristijan, Chau, Trisha, Robinson, Chevalia J., MacDonald, Sandra D., Peterson, Ann M., Mashek, Christine M., Wallin, Windy A., Rimkus, Mark, Montgomery, Frederick, Lucas da Silva, Joas, Gupta, Shashank, Ghaffari, Abdi, Zelazny, Adrian M., Olivier, Kenneth N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Microbiology Society 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656188/
https://www.ncbi.nlm.nih.gov/pubmed/33195983
http://dx.doi.org/10.1099/acmi.0.000154
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author Bogdanovski, Kristijan
Chau, Trisha
Robinson, Chevalia J.
MacDonald, Sandra D.
Peterson, Ann M.
Mashek, Christine M.
Wallin, Windy A.
Rimkus, Mark
Montgomery, Frederick
Lucas da Silva, Joas
Gupta, Shashank
Ghaffari, Abdi
Zelazny, Adrian M.
Olivier, Kenneth N.
author_facet Bogdanovski, Kristijan
Chau, Trisha
Robinson, Chevalia J.
MacDonald, Sandra D.
Peterson, Ann M.
Mashek, Christine M.
Wallin, Windy A.
Rimkus, Mark
Montgomery, Frederick
Lucas da Silva, Joas
Gupta, Shashank
Ghaffari, Abdi
Zelazny, Adrian M.
Olivier, Kenneth N.
author_sort Bogdanovski, Kristijan
collection PubMed
description INTRODUCTION: Mycobacterium abscessus is an emerging pulmonary pathogen with limited treatment options. Nitric oxide (NO) demonstrates antibacterial activity against various bacterial species, including mycobacteria. In this study, we evaluated the effect of adjunctive inhaled NO therapy, using a novel NO generator, in a CF patient with pulmonary M. abscessus disease, and examined heterogeneity of response to NO in vitro. METHODS: In the compassionate-use treatment, a 24-year-old CF patient with pulmonary M. abscessus was treated with two courses of adjunctive intermittent NO, first at 160 p.p.m. for 21 days and subsequently by escalating the dose up to 240 p.p.m. for 8 days. Methemoglobin, pulmonary function, 6 min walk distance (6MWD), qualify of life and sputum microbiology were assessed. In vitro susceptibility tests were performed against patient’s isolate and comparison clinical isolates and quantified by Hill’s slopes calculated from time–kill curves. RESULTS: M. abscessus lung infection eradication was not achieved, but improvements in selected qualify of life domains, lung function and 6MWD were observed during the study. Inhaled NO was well tolerated at 160 p.p.m. Dosing at 240 p.p.m. was stopped due to adverse symptoms, although methemoglobin levels remained within safety thresholds. In vitro susceptibility tests showed a dose-dependent NO effect on M. abscessus susceptibility and significant heterogeneity in response between M. abscessus clinical isolates. The patient’s isolate was found to be the least susceptible strain in vitro. CONCLUSION: These results demonstrate heterogeneity in M. abscessus susceptibility to NO and suggest that longer treatment regimens could be required to see the reduction or eradication of more resistant pulmonary strains.
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spelling pubmed-76561882020-11-12 Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease Bogdanovski, Kristijan Chau, Trisha Robinson, Chevalia J. MacDonald, Sandra D. Peterson, Ann M. Mashek, Christine M. Wallin, Windy A. Rimkus, Mark Montgomery, Frederick Lucas da Silva, Joas Gupta, Shashank Ghaffari, Abdi Zelazny, Adrian M. Olivier, Kenneth N. Access Microbiol Research Article INTRODUCTION: Mycobacterium abscessus is an emerging pulmonary pathogen with limited treatment options. Nitric oxide (NO) demonstrates antibacterial activity against various bacterial species, including mycobacteria. In this study, we evaluated the effect of adjunctive inhaled NO therapy, using a novel NO generator, in a CF patient with pulmonary M. abscessus disease, and examined heterogeneity of response to NO in vitro. METHODS: In the compassionate-use treatment, a 24-year-old CF patient with pulmonary M. abscessus was treated with two courses of adjunctive intermittent NO, first at 160 p.p.m. for 21 days and subsequently by escalating the dose up to 240 p.p.m. for 8 days. Methemoglobin, pulmonary function, 6 min walk distance (6MWD), qualify of life and sputum microbiology were assessed. In vitro susceptibility tests were performed against patient’s isolate and comparison clinical isolates and quantified by Hill’s slopes calculated from time–kill curves. RESULTS: M. abscessus lung infection eradication was not achieved, but improvements in selected qualify of life domains, lung function and 6MWD were observed during the study. Inhaled NO was well tolerated at 160 p.p.m. Dosing at 240 p.p.m. was stopped due to adverse symptoms, although methemoglobin levels remained within safety thresholds. In vitro susceptibility tests showed a dose-dependent NO effect on M. abscessus susceptibility and significant heterogeneity in response between M. abscessus clinical isolates. The patient’s isolate was found to be the least susceptible strain in vitro. CONCLUSION: These results demonstrate heterogeneity in M. abscessus susceptibility to NO and suggest that longer treatment regimens could be required to see the reduction or eradication of more resistant pulmonary strains. Microbiology Society 2020-08-10 /pmc/articles/PMC7656188/ /pubmed/33195983 http://dx.doi.org/10.1099/acmi.0.000154 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License.
spellingShingle Research Article
Bogdanovski, Kristijan
Chau, Trisha
Robinson, Chevalia J.
MacDonald, Sandra D.
Peterson, Ann M.
Mashek, Christine M.
Wallin, Windy A.
Rimkus, Mark
Montgomery, Frederick
Lucas da Silva, Joas
Gupta, Shashank
Ghaffari, Abdi
Zelazny, Adrian M.
Olivier, Kenneth N.
Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease
title Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease
title_full Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease
title_fullStr Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease
title_full_unstemmed Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease
title_short Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease
title_sort antibacterial activity of high-dose nitric oxide against pulmonary mycobacterium abscessus disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656188/
https://www.ncbi.nlm.nih.gov/pubmed/33195983
http://dx.doi.org/10.1099/acmi.0.000154
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