Macrolide resistance in Mycobacterium abscessus: current insights and future perspectives.

Mycobacterium abscessus (MAB) is a rapidly growing, non-tuberculous mycobacterium that has emerged as a significant pathogen in both pulmonary and extrapulmonary infections. It is rising in prevalence, especially among individuals with underlying lung conditions such as cystic fibrosis and chronic obstructive pulmonary disease, highlighting its growing clinical importance. The treatment of MAB infections is notoriously challenging due to intrinsic resistance to many antibiotics and low cure rates, typically <50%. Macrolides are a cornerstone in the treatment of MAB infections because regimens that include effective macrolide therapy are associated with higher cure rates. However, MAB possesses intrinsic and acquired drug resistance mechanisms against macrolides, complicating drug susceptibility testing and selection of highly effective treatment regimens. This review aims to provide a summary of the current understanding of macrolide resistance mechanisms in MAB. We explored the epidemiology of resistance in different countries and the molecular mechanisms involved. We have highlighted the variability in sensitivity of existing markers to predict phenotypic macrolide drug resistance across different countries, suggesting the involvement of unknown resistance mechanisms. By synthesizing current knowledge and identifying gaps in the literature, this review seeks to inform clinical practice and guide future research efforts in the fight against MAB drug resistance.