TASP

The challenge

When new antibiotics are introduced, selection pressures favour the survival of microbes that can tolerate their presence. Over time, drugs lose their effectiveness as a higher proportion of microbes become resistant.

Although it has been used for only a few years, there is accumulating evidence that this is the fate of bedaquiline, a novel TB antibiotic that has become the mainstay of treatment for drug-resistant TB infections. The use of bedaquiline has enabled these treatment programmes to be significantly shortened, from 18 months to 6–9 months. 

The development of resistance can be delayed by careful use of antibiotics, restricting their use to cases where they are most likely to eliminate TB infections. However, it is currently challenging to determine when TB cases might have reduced sensitivity to bedaquiline, and alternative treatments are preferred.

The project

The TASP project is evaluating a combination of innovative approaches to improve the use of bedaquiline in sub-Saharan Africa to preserve its long-term potency.

The first innovation is to use an intensified TB treatment regimen for patients known to have drug-resistant TB infection or at risk of such infection. During this critical time, patients will be given a combination of six drugs, using high-dose options where possible.

In addition, a novel method (thin-layer agar) will be used to rapidly assess the susceptibility of infections to different TB drugs. While conventional tests can take many weeks to provide such information, this new method should provide results within 2–8 weeks.

The third innovation is to develop and apply an AI decision-support tool that will analyse patient data and infection resistance profiles and recommend the most appropriate treatment option. Extensive expert consultations will be organised to agree on which of the four possible treatment regimens is best suited to patients with different patterns of resistance. 

A trial of this strategy will then be organised in Mozambique, Nigeria and South Africa, recruiting patients with an identified bedaquiline- or rifampicin-resistant infection, or who have not responded to rifampicin-based treatment. The trial will focus on treatment success rates, with 60% or higher considered a positive result. 

In parallel, the project will work with local stakeholders to co-develop portable air cleaners using local materials. In addition to capturing airborne pathogens, filters could be analysed to monitor the environment for drug-resistant bacterial strains. This approach was successfully applied during the COVID-19 pandemic, and products built with readily available materials appear to be as effective as commercially produced filters.

Impact

The TASP project will generate key evidence on a possible new bedaquiline stewardship strategy. It will:

• Reveal whether initial intensified treatment of suspected drug-resistant tuberculosis infections leads to better clinical outcomes.
• Demonstrate whether drug-susceptibility data generated using the thin-layer agar method can improve patient management and support more rational antibiotic use.
• Show whether an AI-based clinical decision-support tool enhances bedaquiline stewardship.

More judicious use of bedaquiline through this new approach could improve short-term clinical outcomes and extend its lifespan, thereby maintaining its effectiveness for multidrug-resistant tuberculosis infections.