Recent advances and unmet needs in the treatment of drug-resistant tuberculosis

Drug-resistant tuberculosis (DR-TB) still represents a critical global health threat despite recent therapeutic advances. The shift from long, injectable-based regimens to shorter, all-oral regimens has improved outcomes, yet substantial challenges remain in ensuring efficacy, safety, and equitable access.

We reviewed recent literature (2020-2025) searching PubMed, Medline, Google Scholar, clinicaltrials.gov, WHO guidelines, conference abstract books focusing on recent policy-changing, or knowledge-advancing Phase II/III clinical trials assessing novel DR-TB drugs/regimens.We reported the persisting issues of drug toxicity and acquisition of drug resistance, reviewing evidence from trials, surveillance data, and real-life studies. We provided an overview of new compounds and regimens in the pipeline and underlined the critical role of drug-susceptibility testing.

The availability of multiple short, all-oral regimens offers unprecedented therapeutic opportunities for drug-resistant tuberculosis. At the same time, the rise in bedaquiline resistance hampers the efficacy of these regimens and represents a global health threat. A promising rich pipeline of new compounds under development holds an important transformational potential in TB treatment; however, integrated drug-diagnostic development is needed to avoid past mistakes. Global advocacy for equitable access to TB treatment is fundamental to pairing scientific progress with concrete impact.