Future-proofing tuberculosis therapy: framework for concurrent drug and resistance testing development.

Saluzzo F., Yerlikaya S., Dorman SE., Eisenach K., Farhat MR., Ismail N., Lienhardt C., Walker TM., Jones F., Yepes A., Penn-Nicholson A., Ruhwald M., Kana B., Denkinger CM., Cirillo DM.

The rapid emergence of resistance to novel tuberculosis drugs, such as bedaquiline, is a key threat to the long-term effectiveness of novel regimens. Given that the introduction of these agents has enabled the introduction of an all-oral regimen for rifampicin-resistant and multidrug-resistant tuberculosis, the rise of resistance underscores the urgent need to safeguard their efficacy and responsible use. A major barrier is the delay in developing reliable tools to detect resistance to novel compounds, which limits clinical decision-making and surveillance efforts. Herein, we outline a framework for integrating the development of drug susceptibility testing alongside tuberculosis drug development, including early stage resistance profiling and defining appropriate epidemiological cutoff values. We highlight key gaps, including the need for structured partnerships between drug developers, diagnostic manufacturers, regulators, research institutions, funders, and policy makers. We propose a roadmap to accelerate drug susceptibility testing and development of new tuberculosis regimens, ensuring that resistance detection maintains pace with the introduction of novel drugs. Establishing collaborative platforms for data sharing, genomic analysis, and diagnostic innovation will help ensure that resistance detection evolves in step with drug development, thereby preserving novel treatments and improving global tuberculosis care.

DOI

10.1016/s1473-3099(25)00547-x

Type

Journal article

Publication Date

2026-06-01T00:00:00+00:00

Volume

26

Pages

e248 - e256

Addresses

Vita Salute San Raffaele University, Milan, Italy; IRCCS San Raffaele Scientific Institute, Department of Immunology, Transplantation and Infectious Diseases, Milan, Italy.

Keywords

Humans, Mycobacterium tuberculosis, Tuberculosis, Tuberculosis, Multidrug-Resistant, Antitubercular Agents, Microbial Sensitivity Tests, Drug Resistance, Bacterial, Drug Development

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