Evaluation of the In Vitro Activity of Bedaquiline, Delamanid, and Clofazimine Against <i>Mycobacterium abscessus</i> Complex and Their Antibiofilm Potential

<i>Mycobacterium abscessus</i> complex (MABc) poses a major therapeutic challenge due to its intrinsic multidrug resistance and ability to form biofilms. This study evaluated the in vitro activity of three antimycobacterial agents—bedaquiline, delamanid, and clofazimine—on 20 clinical MA...

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Main Authors: Katarzyna Kania, Katarzyna Wójcik, Alicja Skórkowska, Karolina Klesiewicz
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/14/6/582
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author Katarzyna Kania
Katarzyna Wójcik
Alicja Skórkowska
Karolina Klesiewicz
author_facet Katarzyna Kania
Katarzyna Wójcik
Alicja Skórkowska
Karolina Klesiewicz
author_sort Katarzyna Kania
collection DOAJ
description <i>Mycobacterium abscessus</i> complex (MABc) poses a major therapeutic challenge due to its intrinsic multidrug resistance and ability to form biofilms. This study evaluated the in vitro activity of three antimycobacterial agents—bedaquiline, delamanid, and clofazimine—on 20 clinical MABc isolates, including <i>M. abscessus</i> subsp. <i>abscessus</i>, <i>massiliense</i>, and <i>bolletii</i>, with a focus on biofilm-forming phenotypes. Biofilm analysis showed that the rough colony morphotypes were mostly weak biofilm formers, while the smooth and mixed morphotypes were predominantly moderate or strong biofilm formers. A statistically significant association was observed between the mixed colony morphology and strong biofilm formation (<i>p</i> = 0.032). Importantly, bedaquiline exhibited potent and consistent activity across all isolates, regardless of the biofilm-forming ability, with MIC values ranging from 0.125 to 1 µg/mL. In contrast, delamanid and clofazimine showed limited efficacy, with MIC values exceeding 16 µg/mL and 8 µg/mL, respectively. These findings strongly support the role of bedaquiline as a promising core agent for future combination therapies targeting drug-resistant MABc infections, including biofilm-associated infections. Our results, among the first from Poland, highlight the critical need for incorporating novel agents such as bedaquiline into therapeutic strategies against this difficult-to-treat pathogen.
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spelling doaj-art-4ac6d63e9500488a85e241350d3eefce2025-08-20T03:29:35ZengMDPI AGPathogens2076-08172025-06-0114658210.3390/pathogens14060582Evaluation of the In Vitro Activity of Bedaquiline, Delamanid, and Clofazimine Against <i>Mycobacterium abscessus</i> Complex and Their Antibiofilm PotentialKatarzyna Kania0Katarzyna Wójcik1Alicja Skórkowska2Karolina Klesiewicz3Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Jagiellonian University Medical College, St. Medyczna 9, 30-688 Krakow, PolandMalopolska Central Laboratory of Tuberculosis Diagnostics, The St. John Paul II Specialist Hospital, St. Ulanow 29, 31-455 Krakow, PolandBioImaging Laboratory, Center for the Development of Therapies for Civilization and Age-Related Diseases, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, PolandDepartment of Pharmaceutical Microbiology, Faculty of Pharmacy, Jagiellonian University Medical College, St. Medyczna 9, 30-688 Krakow, Poland<i>Mycobacterium abscessus</i> complex (MABc) poses a major therapeutic challenge due to its intrinsic multidrug resistance and ability to form biofilms. This study evaluated the in vitro activity of three antimycobacterial agents—bedaquiline, delamanid, and clofazimine—on 20 clinical MABc isolates, including <i>M. abscessus</i> subsp. <i>abscessus</i>, <i>massiliense</i>, and <i>bolletii</i>, with a focus on biofilm-forming phenotypes. Biofilm analysis showed that the rough colony morphotypes were mostly weak biofilm formers, while the smooth and mixed morphotypes were predominantly moderate or strong biofilm formers. A statistically significant association was observed between the mixed colony morphology and strong biofilm formation (<i>p</i> = 0.032). Importantly, bedaquiline exhibited potent and consistent activity across all isolates, regardless of the biofilm-forming ability, with MIC values ranging from 0.125 to 1 µg/mL. In contrast, delamanid and clofazimine showed limited efficacy, with MIC values exceeding 16 µg/mL and 8 µg/mL, respectively. These findings strongly support the role of bedaquiline as a promising core agent for future combination therapies targeting drug-resistant MABc infections, including biofilm-associated infections. Our results, among the first from Poland, highlight the critical need for incorporating novel agents such as bedaquiline into therapeutic strategies against this difficult-to-treat pathogen.https://www.mdpi.com/2076-0817/14/6/582<i>Mycobacterium abscessus</i> complexnon-tuberculous mycobacteriabedaquilinebiofilm formation
spellingShingle Katarzyna Kania
Katarzyna Wójcik
Alicja Skórkowska
Karolina Klesiewicz
Evaluation of the In Vitro Activity of Bedaquiline, Delamanid, and Clofazimine Against <i>Mycobacterium abscessus</i> Complex and Their Antibiofilm Potential
Pathogens
<i>Mycobacterium abscessus</i> complex
non-tuberculous mycobacteria
bedaquiline
biofilm formation
title Evaluation of the In Vitro Activity of Bedaquiline, Delamanid, and Clofazimine Against <i>Mycobacterium abscessus</i> Complex and Their Antibiofilm Potential
title_full Evaluation of the In Vitro Activity of Bedaquiline, Delamanid, and Clofazimine Against <i>Mycobacterium abscessus</i> Complex and Their Antibiofilm Potential
title_fullStr Evaluation of the In Vitro Activity of Bedaquiline, Delamanid, and Clofazimine Against <i>Mycobacterium abscessus</i> Complex and Their Antibiofilm Potential
title_full_unstemmed Evaluation of the In Vitro Activity of Bedaquiline, Delamanid, and Clofazimine Against <i>Mycobacterium abscessus</i> Complex and Their Antibiofilm Potential
title_short Evaluation of the In Vitro Activity of Bedaquiline, Delamanid, and Clofazimine Against <i>Mycobacterium abscessus</i> Complex and Their Antibiofilm Potential
title_sort evaluation of the in vitro activity of bedaquiline delamanid and clofazimine against i mycobacterium abscessus i complex and their antibiofilm potential
topic <i>Mycobacterium abscessus</i> complex
non-tuberculous mycobacteria
bedaquiline
biofilm formation
url https://www.mdpi.com/2076-0817/14/6/582
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