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Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease

BACKGROUND: A three-drug regimen (macrolide, ethambutol, and rifampicin) is recommended for the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Although macrolide has proven efficacy, the role of ethambutol and rifampicin in patients without acquired immune deficiency syndrome i...

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Autores principales: Kim, Hyung-Jun, Lee, Jong Sik, Kwak, Nakwon, Cho, Jaeyoung, Lee, Chang-Hoon, Han, Sung Koo, Yim, Jae-Joon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849249/
https://www.ncbi.nlm.nih.gov/pubmed/31711459
http://dx.doi.org/10.1186/s12890-019-0982-8
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author Kim, Hyung-Jun
Lee, Jong Sik
Kwak, Nakwon
Cho, Jaeyoung
Lee, Chang-Hoon
Han, Sung Koo
Yim, Jae-Joon
author_facet Kim, Hyung-Jun
Lee, Jong Sik
Kwak, Nakwon
Cho, Jaeyoung
Lee, Chang-Hoon
Han, Sung Koo
Yim, Jae-Joon
author_sort Kim, Hyung-Jun
collection PubMed
description BACKGROUND: A three-drug regimen (macrolide, ethambutol, and rifampicin) is recommended for the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Although macrolide has proven efficacy, the role of ethambutol and rifampicin in patients without acquired immune deficiency syndrome is not proven with clinical studies. We aimed to clarify the roles of ethambutol and rifampicin in the treatment of MAC-PD. METHODS: Patients treated for MAC-PD between March 1st, 2009 and October 31st, 2018 were reviewed retrospectively. Rates of culture conversion, microbiological cure, treatment failure, and recurrence were compared according to the maintenance (≥6 months) of ethambutol or rifampicin with macrolide. RESULTS: Among the 237 patients, 122 (51.5%) maintained ethambutol and rifampicin with macrolide, 58 (24.5%) maintained ethambutol and macrolide, 32 (13.5%) maintained rifampicin and macrolide, and 25 (10.6%) maintained macrolide only. Culture conversion was reached for 190/237 (80.2%) patients and microbiological cure was achieved for 129/177 (72.9%) who completed the treatment. Treatment failure despite ≥12 months of treatment was observed in 66/204 (32.4%), and recurrence was identified in 16/129 (12.4%) who achieved microbiological cure. Compared with maintenance of macrolide only, maintenance of ethambutol, rifampicin or both with macrolide were associated with higher odds of culture conversion [odds ratio (OR), 95% confidence interval (CI): 18.06, 3.67–88.92; 15.82, 2.38–105.33; and 17.12, 3.93–74.60, respectively]. Higher odds of microbiological cure were associated with maintenance of both ethambutol and rifampicin with macrolide (OR, 95% CI: 5.74, 1.54–21.42) and macrolide and ethambutol (OR, 95% CI: 5.12, 1.72–15.24) but not macrolide and rifampicin. Maintenance of both ethambutol and rifampicin with macrolide was associated with lower odds of treatment failure (OR, 95% CI: 0.09, 0.01–0.53) compared with macrolide only, while maintenance of one of these with macrolide was not. Maintenance of both ethambutol and rifampicin or one of these with macrolide did not decrease the probability of recurrence when compared with macrolide only. CONCLUSIONS: Maintenance (≥6 months) of ethambutol and rifampicin with macrolide was associated with the most favorable treatment outcomes among patients with MAC-PD. Given the association between ongoing ethambutol use and microbiological cure, clinicians should maintain ethambutol unless definite adverse events develop.
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spelling pubmed-68492492019-11-15 Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease Kim, Hyung-Jun Lee, Jong Sik Kwak, Nakwon Cho, Jaeyoung Lee, Chang-Hoon Han, Sung Koo Yim, Jae-Joon BMC Pulm Med Research Article BACKGROUND: A three-drug regimen (macrolide, ethambutol, and rifampicin) is recommended for the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Although macrolide has proven efficacy, the role of ethambutol and rifampicin in patients without acquired immune deficiency syndrome is not proven with clinical studies. We aimed to clarify the roles of ethambutol and rifampicin in the treatment of MAC-PD. METHODS: Patients treated for MAC-PD between March 1st, 2009 and October 31st, 2018 were reviewed retrospectively. Rates of culture conversion, microbiological cure, treatment failure, and recurrence were compared according to the maintenance (≥6 months) of ethambutol or rifampicin with macrolide. RESULTS: Among the 237 patients, 122 (51.5%) maintained ethambutol and rifampicin with macrolide, 58 (24.5%) maintained ethambutol and macrolide, 32 (13.5%) maintained rifampicin and macrolide, and 25 (10.6%) maintained macrolide only. Culture conversion was reached for 190/237 (80.2%) patients and microbiological cure was achieved for 129/177 (72.9%) who completed the treatment. Treatment failure despite ≥12 months of treatment was observed in 66/204 (32.4%), and recurrence was identified in 16/129 (12.4%) who achieved microbiological cure. Compared with maintenance of macrolide only, maintenance of ethambutol, rifampicin or both with macrolide were associated with higher odds of culture conversion [odds ratio (OR), 95% confidence interval (CI): 18.06, 3.67–88.92; 15.82, 2.38–105.33; and 17.12, 3.93–74.60, respectively]. Higher odds of microbiological cure were associated with maintenance of both ethambutol and rifampicin with macrolide (OR, 95% CI: 5.74, 1.54–21.42) and macrolide and ethambutol (OR, 95% CI: 5.12, 1.72–15.24) but not macrolide and rifampicin. Maintenance of both ethambutol and rifampicin with macrolide was associated with lower odds of treatment failure (OR, 95% CI: 0.09, 0.01–0.53) compared with macrolide only, while maintenance of one of these with macrolide was not. Maintenance of both ethambutol and rifampicin or one of these with macrolide did not decrease the probability of recurrence when compared with macrolide only. CONCLUSIONS: Maintenance (≥6 months) of ethambutol and rifampicin with macrolide was associated with the most favorable treatment outcomes among patients with MAC-PD. Given the association between ongoing ethambutol use and microbiological cure, clinicians should maintain ethambutol unless definite adverse events develop. BioMed Central 2019-11-11 /pmc/articles/PMC6849249/ /pubmed/31711459 http://dx.doi.org/10.1186/s12890-019-0982-8 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kim, Hyung-Jun
Lee, Jong Sik
Kwak, Nakwon
Cho, Jaeyoung
Lee, Chang-Hoon
Han, Sung Koo
Yim, Jae-Joon
Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease
title Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease
title_full Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease
title_fullStr Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease
title_full_unstemmed Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease
title_short Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease
title_sort role of ethambutol and rifampicin in the treatment of mycobacterium avium complex pulmonary disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849249/
https://www.ncbi.nlm.nih.gov/pubmed/31711459
http://dx.doi.org/10.1186/s12890-019-0982-8
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