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The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex

BACKGROUND: Nontuberculous mycobacteria (NTM) are ubiquitous organisms and the incidence of NTM infections has been increasing in recent years. Mycobacteroides abscessus (M. abscessus) is one of the most antimicrobial-resistant NTM; however, no reliable antibiotic regimen can be officially advocated...

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Autores principales: Takei, Satomi, Ihara, Hiroaki, Togo, Shinsaku, Nakamura, Ayako, Fujimoto, Yuichi, Watanabe, Junko, Kurokawa, Kana, Shibayama, Kohei, Sumiyoshi, Issei, Ochi, Yusuke, Iwai, Moe, Okabe, Takahiro, Chonan, Masayoshi, Misawa, Shigeki, Ohsaka, Akimichi, Takahashi, Kazuhisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574464/
https://www.ncbi.nlm.nih.gov/pubmed/33076820
http://dx.doi.org/10.1186/s12866-020-02000-5
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author Takei, Satomi
Ihara, Hiroaki
Togo, Shinsaku
Nakamura, Ayako
Fujimoto, Yuichi
Watanabe, Junko
Kurokawa, Kana
Shibayama, Kohei
Sumiyoshi, Issei
Ochi, Yusuke
Iwai, Moe
Okabe, Takahiro
Chonan, Masayoshi
Misawa, Shigeki
Ohsaka, Akimichi
Takahashi, Kazuhisa
author_facet Takei, Satomi
Ihara, Hiroaki
Togo, Shinsaku
Nakamura, Ayako
Fujimoto, Yuichi
Watanabe, Junko
Kurokawa, Kana
Shibayama, Kohei
Sumiyoshi, Issei
Ochi, Yusuke
Iwai, Moe
Okabe, Takahiro
Chonan, Masayoshi
Misawa, Shigeki
Ohsaka, Akimichi
Takahashi, Kazuhisa
author_sort Takei, Satomi
collection PubMed
description BACKGROUND: Nontuberculous mycobacteria (NTM) are ubiquitous organisms and the incidence of NTM infections has been increasing in recent years. Mycobacteroides abscessus (M. abscessus) is one of the most antimicrobial-resistant NTM; however, no reliable antibiotic regimen can be officially advocated. We evaluated the efficacy of clarithromycin in combination with various antimicrobial agents against the M. abscessus complex. RESULTS: Twenty-nine clinical strains of M. abscessus were isolated from various clinical samples. Of the isolates, 10 (34.5%) were of M. abscessus subsp. abscessus, 18 (62.1%) of M. abscessus subsp. massiliense, and 1 (3.4%) of M. abscessus subsp. bolletii. MICs of three antimicrobial agents (amikacin, imipenem, and moxifloxacin) were measured with or without clarithromycin. The imipenem-clarithromycin combination significantly reduced MICs compared to clarithromycin and imipenem monotherapies, including against resistant strains. The association between susceptibility of the M. abscessus complex and each combination of agents was significant (p = 0.001). Adjusted residuals indicated that the imipenem-clarithromycin combination had the synergistic effect (adjusted residual = 3.1) and suppressed the antagonistic effect (adjusted residual = − 3.1). In subspecies of M. abscessus complex, the association with susceptibility of M. abscessus subsp. massiliense was similarly statistically significant (p = 0.036: adjusted residuals of synergistic and antagonistic effect respectively: 2.6 and − 2.6). The association with susceptibility of M. abscessus subsp. abscessus also showed a similar trend but did not reach statistical significance. CONCLUSION: Our data suggest that the imipenem-clarithromycin combination could be the recommended therapeutic choice for the treatment of M. abscessus complex owing to its ability to restore antimicrobial susceptibility.
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spelling pubmed-75744642020-10-20 The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex Takei, Satomi Ihara, Hiroaki Togo, Shinsaku Nakamura, Ayako Fujimoto, Yuichi Watanabe, Junko Kurokawa, Kana Shibayama, Kohei Sumiyoshi, Issei Ochi, Yusuke Iwai, Moe Okabe, Takahiro Chonan, Masayoshi Misawa, Shigeki Ohsaka, Akimichi Takahashi, Kazuhisa BMC Microbiol Research Article BACKGROUND: Nontuberculous mycobacteria (NTM) are ubiquitous organisms and the incidence of NTM infections has been increasing in recent years. Mycobacteroides abscessus (M. abscessus) is one of the most antimicrobial-resistant NTM; however, no reliable antibiotic regimen can be officially advocated. We evaluated the efficacy of clarithromycin in combination with various antimicrobial agents against the M. abscessus complex. RESULTS: Twenty-nine clinical strains of M. abscessus were isolated from various clinical samples. Of the isolates, 10 (34.5%) were of M. abscessus subsp. abscessus, 18 (62.1%) of M. abscessus subsp. massiliense, and 1 (3.4%) of M. abscessus subsp. bolletii. MICs of three antimicrobial agents (amikacin, imipenem, and moxifloxacin) were measured with or without clarithromycin. The imipenem-clarithromycin combination significantly reduced MICs compared to clarithromycin and imipenem monotherapies, including against resistant strains. The association between susceptibility of the M. abscessus complex and each combination of agents was significant (p = 0.001). Adjusted residuals indicated that the imipenem-clarithromycin combination had the synergistic effect (adjusted residual = 3.1) and suppressed the antagonistic effect (adjusted residual = − 3.1). In subspecies of M. abscessus complex, the association with susceptibility of M. abscessus subsp. massiliense was similarly statistically significant (p = 0.036: adjusted residuals of synergistic and antagonistic effect respectively: 2.6 and − 2.6). The association with susceptibility of M. abscessus subsp. abscessus also showed a similar trend but did not reach statistical significance. CONCLUSION: Our data suggest that the imipenem-clarithromycin combination could be the recommended therapeutic choice for the treatment of M. abscessus complex owing to its ability to restore antimicrobial susceptibility. BioMed Central 2020-10-19 /pmc/articles/PMC7574464/ /pubmed/33076820 http://dx.doi.org/10.1186/s12866-020-02000-5 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Research Article
Takei, Satomi
Ihara, Hiroaki
Togo, Shinsaku
Nakamura, Ayako
Fujimoto, Yuichi
Watanabe, Junko
Kurokawa, Kana
Shibayama, Kohei
Sumiyoshi, Issei
Ochi, Yusuke
Iwai, Moe
Okabe, Takahiro
Chonan, Masayoshi
Misawa, Shigeki
Ohsaka, Akimichi
Takahashi, Kazuhisa
The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex
title The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex
title_full The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex
title_fullStr The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex
title_full_unstemmed The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex
title_short The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex
title_sort synergetic effect of imipenem-clarithromycin combination in the mycobacteroides abscessus complex
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574464/
https://www.ncbi.nlm.nih.gov/pubmed/33076820
http://dx.doi.org/10.1186/s12866-020-02000-5
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