In 2022, the World Health Organization transformed the treatment of tuberculosis (TB). It recommended a six-month course of antibiotic pills that include the drug bedaquiline. This is more effective, cheaper and faster to implement than was the old regimen, which took up to 20 months and involved injecting medicines with bad side effects, including hearing loss.

But this treatment is already under threat. Drug resistance is being seen, risking the world reverting to longer, more complex and expensive treatments for TB. A concerning factor is that researchers still have limited understanding of how and why resistance arises.

TB remains the world’s leading infectious-disease killer, causing 1.23 million deaths in 2024. The bacterium that causes the disease can evolve rapidly when it is exposed to a new drug, to evade it. Each medicine that is introduced starts a ticking clock in the race against drug-resistant strains — and a race to understand how resistance emerges.

The rise of ‘nightmare bacteria’: antimicrobial resistance in five charts

Researchers should think about antimicrobial research and development (R&D) not simply as a pipeline of new medicines, but as a balance between developing treatments and understanding how to preserve those we already have before resistance renders them useless.

A drug regimen that has promising results in clinical trials, or even one that works brilliantly at a population level, can still fail if we don’t understand which combinations of medicines, genetic changes in bacteria and treatment conditions allow resistance to emerge.

We need the science that tells us how to use a medicine well, how resistance might be or already is emerging, who is most at risk and how quickly we need to change course to prevent further resistance spread — this evidence generation must all come as part of the innovation process, not after.

For new TB drugs to have lasting impact, R&D needs to include surveillance, genomics, diagnostics, clinical evidence of patient outcomes and implementation research, alongside drug discovery. Research into how existing drugs are used, monitored, optimized and preserved deserves as much support as drug development does.

Stop delaying action on antimicrobial resistance — it is achievable and affordable

Yet limited availability of surveillance and drug-susceptibility data makes it hard to fully quantify the prevalence of drug-resistant TB, including resistance to bedaquiline-based regimens. Without such data, it is difficult to spot trends and patterns of drug resistance.

Genome sequencing is another crucial tool in understanding how resistance occurs. As treatments improve, researchers need to keep pace by understanding how the genetic make-up of the bacterium influences how it responds to specific drugs, and ultimately what that means for patient outcomes. And this technology needs to be made available and accessible in countries with high disease burden.

TB treatment can be a stab in the dark — a case of trying a drug combination and waiting to see if it works for an individual. This can allow resistance to spread undetected before clinicians realize that the treatment is ineffective. If researchers can identify resistance earlier and understand which drug combinations are most likely to work against a person’s infection, we can stop treating people with medicines that their bacteria can already evade.