Drug-Resistant Tuberculosis at the Crossroads: Molecular Insights and Next-Generation Therapeutics

Tuberculosis (TB) growing prevalence of drug-resistant strains Mycobacterium tuberculosis, it continues to major worldwide disease and a major public health concern. Emergence of Extensively Drug-Resistant (XDR-TB), Multidrug-Resistant (MDR-TB) tuberculosis has confounded disease management globally and dramatically decreased the efficacy of traditional anti-tubercular therapy. Drug resistance mainly occurs through genetic mutations, improper drug usage, poor patient compliance, prolonged treatment duration, and activation of resistance mechanisms such as efflux pumps. They play an important role reducing intracellular drug concentration, thereby decreasing therapeutic efficacy and promoting multidrug resistance. This review summarizes the pathogenesis of tuberculosis, mechanisms of anti-tubercular drug resistance, and the contribution efflux pumps resistant TB strains. It also highlights current diagnostic approaches, including molecular and phenotypic techniques used for early detection of resistant tuberculosis. In addition, emerging therapeutic strategies such as efflux pump inhibitors, novel anti-tubercular agents, combination therapy, are discussed as promising approaches for overcoming drug resistance. Despite recent advances, challenges including prolonged treatment duration, adverse drug reactions, treatment failure, and limited diagnostic accessibility continue to affect TB control programs. This emphasizes the importance of early diagnosis, effective therapeutic strategies, and continued research to combat drug-resistant tuberculosis and reduce its global burden.