Innovative Approaches to The Diagnosis and Management of Multidrug-Resistant and Rifampicin-Resistant Tuberculosis: Current Challenges and Future Perspectives

Multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) remains a significant obstacle to global efforts in controlling TB, hindering advancements toward elimination goals. The emergence of MDR/RR-TB is mainly due to chromosomal mutations such as rpoB (rifampicin), katG/inhA (isoniazid), pncA (pyrazinamide), and gyrA/gyrB (fluoroquinolones), in conjunction with bacterial survival strategies like efflux pumps and dormancy. The heaviest impact is felt in low- and middle-income nations, where issues like poverty, co-infection with HIV, malnutrition, and weak healthcare systems worsen transmission rates and mortality. Diagnostic capabilities have improved with molecular technologies such as Xpert MTB/RIF, Xpert MTB/XDR, and Line Probe Assays, which allow for quicker detection of resistance compared to traditional culture methods. Whole Genome Sequencing provides extensive profiling and monitoring advantages, but its high cost and infrastructure needs limit its broad application. Treatment strategies have shifted from long, toxic injectable regimens to all-oral, more condensed options that include new drugs like bedaquiline, delamanid, pretomanid, and linezolid. The WHO now supports six- to nine-month treatment regimens like BPaLM that enhance outcomes and patient adherence. However, concerns about toxicity, the development of resistance to new medications, and limited access persist as critical challenges. Future approaches should prioritize affordable diagnostic tools, innovative treatment options, therapies aimed at host responses, digital tools for adherence, and enhanced global cooperation to ensure equitable access and continued progress toward the End TB objectives.