# Evaluation of the In Vitro Activity of Bedaquiline, Delamanid, and Clofazimine Against Mycobacterium abscessus Complex and Their Antibiofilm Potential

## TL;DR

This study tests three drugs against Mycobacterium abscessus, finding that bedaquiline is effective even against biofilm-forming strains.

## Contribution

The study is among the first from Poland to evaluate bedaquiline's efficacy against MABc biofilms and drug resistance.

## Key findings

- Bedaquiline showed potent and consistent activity against all MABc isolates with MIC values from 0.125 to 1 µg/mL.
- Delamanid and clofazimine had limited efficacy with MIC values exceeding 8 µg/mL.
- Mixed colony morphotypes were associated with strong biofilm formation (p = 0.032).

## Abstract

Mycobacterium abscessus 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 M. abscessus subsp. abscessus, massiliense, and bolletii, 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 (p = 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.