Can Diagnostic Delay Amplify Drug Resistance in Tuberculosis? A Critical Integrative Reflection on Bacterial Adaptation, Persistence, Within-Host Evolution, and Heteroresistance

Background/objectives

Drug resistance in tuberculosis remains one of the major challenges to global disease control. Traditionally, its emergence has been attributed to factors such as treatment interruption, poor adherence, and the selective pressure exerted by antimicrobial agents. However, recent advances in bacterial genetics, within-host evolution, cellular persistence, and heteroresistance suggest that relevant biological processes may develop before treatment initiation. The aim of this critical integrative reflection was to explore the biological plausibility that diagnostic delay may act as an amplifying factor for adaptive and evolutionary mechanisms potentially associated with drug resistance in Mycobacterium tuberculosis.