Emerging Therapeutic Approaches to Drug-Resistant Tuberculosis: Compressive Review

Introduction: Drug-resistant tuberculosis (TB), including multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB), poses major global health challenges. Conventional regimens achieve only 50-60% success rates compared to 85% in drug-susceptible TB. This review examines recent therapeutic advances in drug-resistant TB management, focusing on novel and repurposed agents, their mechanisms, clinical efficacy, and integration into optimized treatment regimens. Methods: We conducted a systematic literature search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception to December 2024. Search terms included "multidrug- resistant tuberculosis", "bedaquiline", "delamanid", "pretomanid", and "clinical trials". We included peer-reviewed studies, systematic reviews, meta-analyses, and clinical trial reports, prioritizing high-quality evidence from randomized controlled trials and prospective cohort studies. Data extraction focused on drug mechanisms, clinical outcomes, safety profiles, and resistance patterns. Results: Analysis of 125 studies and 15 ongoing clinical trials demonstrated substantial therapeutic improvements. Novel agents achieved treatment success rates of 73-90% compared to 50-60% with conventional second-line regimens. The BPaL regimen (bedaquiline, pretomanid, linezolid) showed 89-90% favorable outcomes within 6 months compared to traditional 18-24 month durations. Delamanid demonstrated a 73.1% success rate with culture conversion rates of 61-95%. However, bedaquiline resistance increased to 5.7% globally, reaching 14% in high-burden regions. Discussion: Novel therapeutic agents represent transformative advances in drug-resistant TB management, enabling shortened all-oral regimens that address critical barriers, including adherence, toxicity, and healthcare burden. However, rising resistance underscores the need for stewardship and innovation. Conclusion: Bedaquiline, delamanid, and pretomanid have revolutionized drug-resistant TB treatment outcomes, positioning the field toward effective universal treatment access and TB elimination goals.