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Beyond Speed: Why Expanded Drug Resistance Testing Is the Next Frontier in Tuberculosis Diagnostics
A recent article by Saluzzo F and colleagues, published in the Lancet Infectious Diseases argues that tuberculosis drug-susceptibility testing must be developed alongside new drugs and regimens, rather than years after their introduction. The framework described by the authors addresses a growing weakness in TB care: therapeutic innovation can move faster than the tools needed to detect resistance and guide the responsible use of new medicines.
For more than two decades, innovation in tuberculosis (TB) diagnostics has been defined by speed. Rapid molecular tests transformed patient care by enabling early detection of Mycobacterium tuberculosis and rifampicin resistance, dramatically improving the diagnosis and management of multidrug-resistant TB (MDR-TB).
Today, however, the challenge has changed. As modern treatment regimens increasingly rely on bedaquiline, linezolid, pretomanid and fluoroquinolones, clinicians need more than rapid diagnosis, they need rapid insight into which drugs will remain effective for each patient. This marks the beginning of a new era in TB diagnostics: expanded drug resistance testing.
A New Diagnostic Challenge
The introduction of all-oral regimens has revolutionized MDR-TB treatment and improved patient outcomes worldwide. However, the emergence of resistance to key drugs such as bedaquiline threatens these advances. Recent experts have highlighted that while novel drugs reach clinical practice, the development of reliable drug susceptibility tests (DST) often lags behind, limiting clinicians’ ability to optimise treatment and monitor emerging resistance.
The result is a growing mismatch between therapeutic innovation and diagnostic capability.
From Detecting Disease to Guiding Therapy
TB diagnostics have evolved in stages. Initially, the focus was detecting TB itself. Molecular assays then enabled rapid identification of rifampicin resistance, followed by tests for fluoroquinolone resistance that supported management of pre-XDR-TB.
The next step is different. Instead of identifying resistance to a single drug, diagnostics must provide a comprehensive resistance profile that helps clinicians determine whether a patient can safely receive the most effective treatment regimen.
This is the foundation of precision medicine in tuberculosis.
Drug and Diagnostics Must Evolve Together
The recent Lancet framework proposes that drug susceptibility testing should no longer be developed years after new drugs are introduced. Instead, resistance testing should begin during drug development itself through early phenotypic studies, genomic characterisation of resistance mechanisms, and parallel development of molecular diagnostics.
This proactive approach allows resistance detection to keep pace with therapeutic innovation rather than reacting after resistance has already emerged.
Why Flexibility Matters
Resistance to newer drugs is often genetically more complex than resistance to rifampicin, involving multiple genes and diverse mutation patterns. Consequently, future diagnostics will require flexible molecular strategies capable of incorporating new resistance markers as scientific understanding evolves.
In this environment, adaptable, non-proprietary molecular platforms offer an important advantage. Rather than requiring entirely new systems whenever resistance targets expand, open platforms allow laboratories to update assays while continuing to use existing infrastructure, an important consideration for national TB programmes and high-burden countries.
A Collaborative Future
Protecting the effectiveness of new TB drugs requires more than innovative assays. It demands collaboration between pharmaceutical companies, diagnostic developers, researchers, regulators, national TB programmes and global health organisations. The Lancet framework calls for coordinated development of drugs and diagnostics, supported by shared genomic data, surveillance systems and collaborative research partnerships.
Such collaboration will be essential to preserving the effectiveness of new treatment regimens and preventing the spread of drug-resistant TB.
Looking Ahead
The future of TB diagnostics is no longer defined solely by speed.
It will be defined by the ability to provide comprehensive resistance intelligence that supports personalised treatment decisions and protects the effectiveness of life-saving therapies.
Expanded drug resistance testing represents the next major step in precision tuberculosis care. As treatment regimens continue to evolve, diagnostics must evolve with them, ensuring that every therapeutic advance is matched by equally innovative and adaptable resistance testing.
Source
Saluzzo F, Yerlikaya S, Dorman SE, et al. Future-Proofing TB Therapy: Framework for Concurrent Drug and Resistance Testing Development. Lancet Infect Dis. 2026;26(6):e248-e256.