Challenges and therapeutic strategies in nontuberculous mycobacterial infections related to biofilms

INTRODUCTION: Nontuberculous mycobacteria (NTM) are increasingly recognized as clinically significant pathogens, particularly in immunocompromised individuals and patients with chronic lung disease. A key determinant of their persistence and pathogenicity is the ability to form biofilms. It is important to distinguish biofilm-associated phenotypic tolerance (persistence) from genetic antimicrobial resistance. Biofilm-related persistence is transient and non-genetic, while genetic resistance involves stable heritable changes. Both mechanisms contribute to treatment failure and prolonged infection. AREAS COVERED: This review addresses the clinical and therapeutic challenges posed by biofilm-associated NTM infections. We discuss conventional multidrug regimens, the limitations imposed by biofilm physiology, and novel interventions under investigation, including enzymatic biofilm disruption, nanoparticle-based drug delivery, and bacteriophage therapy. Understanding these therapeutic paradigms in the context of biofilm biology is essential for improving outcomes in these difficult-to-treat infections.Given the growing clinical relevance of these organisms, this review primarily examines therapeutic strategies for biofilm-associated NTM infections, while also considering epidemiological and diagnostic aspects to contextualize treatment challenges. EXPERT OPINION: Treatment of biofilm-related NTM infections is extremely difficult to cure, and they usually need the implication of a multidisciplinary team for the best management of these infections, while the cure of the patients is, in many cases, impossible.