FUTURE DIRECTIONS IN TREATING MULTIDRUG- AND EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS: NEW AND BREAKTHROUGH REGIMENS
Abstract
Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis represent escalating global health threats, driven by ongoing transmission, diagnostic limitations, and historically inadequate treatment options. Conventional treatment approaches required prolonged courses spanning 6-24 months, characterized by substantial toxicity and poor treatment outcomes.The therapeutic landscape has undergone a significant transformation over the past decade with the introduction of novel antimycobacterial agents, including bedaquiline, delamanid, and pretomanid, alongside repurposed companion drugs such as linezolid, moxifloxacin, and clofazimine. These advances have enabled the development of shorter, all-oral regimens that substantially reduce patient burden while improving cure rates. The BPaL regimen (bedaquiline, pretomanid, linezolid) and its modification BPaLM (incorporating moxifloxacin) represents landmark achievements, offering effective treatment within shortened timeframes. Complementary approaches, including host-directed therapies, aim to enhance immune responses and minimize tissue pathology to prevent treatment failure and relapse.Despite these therapeutic advances, significant implementation challenges persist. Key concerns include drug safety profiles, equitable access in resource-limited settings, integration with HIV care, comprehensive resistance monitoring, and addressing systemic health inequities that perpetuate disease transmission.This review examines the pathogenesis and epidemiology of drug-resistant tuberculosis within programmatic contexts, evaluates current treatment paradigms and emerging innovations, discusses supportive care strategies, and synthesizes evidence regarding novel regimens and adjunctive therapeutic approaches.
Keywordsmultidrug-resistant tuberculosis, MDR-TB, XDR-TB, BPaL, BPaLM, bedaquiline, pretomanid, linezolid, host-directed therapy, antimicrobial resistance, TB treatment guidelines, short-course regimens
