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image of Emerging Therapeutic Approaches to Drug-Resistant Tuberculosis: Compressive Review

Abstract

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.

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2025-08-29
2025-09-17

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Emerging Therapeutic Approaches to Drug-Resistant Tuberculosis: Compressive Review
Bentham Science Publishers ; https://doi.org/10.2174/011573398X409282250823051901
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/content/journals/crmr/10.2174/011573398X409282250823051901
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  • Article Type:     Review Article
Keywords: novel TB therapeutics ; delamanid ; Extensively drug-resistant TB (XDR-TB) ; pretomanid ; repurposed anti-TB drugs ; clinical trials ; bedaquiline ; Multidrug-resistant tuberculosis (MDR-TB)

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