Research breakthrough in the treatment of drug-resistant tuberculosis

Every year, more than 1.3 million people die from tuberculosis, making it the world's deadliest infectious disease. The fact that only a handful drugs have been developed against tuberculosis since the 1960s and that the disease mainly occurs in low-income countries with limited access to healthcare adds to the challenge, but now researchers have published results in The Lancet Infectious Diseases with the potential to pave the way for more effective and safer treatments.

“To cure tuberculosis requires long antibiotic treatments. In infections caused by multidrug-resistant bacteria, these often include linezolid, an effective drug but with severe side effects that sometime result in discontinued treatments. Therefore, in two clinical phase 2b studies conducted in Tanzania and South Africa, we have used delpazolid and sutezolid – two new drug candidates in the same class as linezolid – to treat drug-resistant tuberculosis, and can now show that patients respond positively,” says Elin Svensson, Professor of Pharmacometrics at Uppsala University.

In the first study, 76 participants were treated with varying drug regimens of delpazolid, with results showing that a daily dose of 1200 mg achieve the desired effect with only a minimum of side effects. In the second study, 75 participants received a combination treatment including sutezolid and three additional drugs. Here, enhanced efficacy was observed without causing nerve damage, although the researchers noted minor side effects on the liver and heart rhythm.

“That linezolid may cause, among other things, a loss of sensation in hands and feet, and that many residents of the countries most affected by tuberculosis have a long way to health clinics prompts the search for a suitable alternative to cure tuberculosis. Our results confirm that both delpazolid and sutezolid offer promising alternatives, but follow-up studies are required to determine optimal dosing and long-term effects,” says Jodie Schildkraut, researcher at Radboud University Medical Center and project coordinator of the EDCTP funded consortium PanACEA that implemented the studies.

Elin Svensson, who led the team's work on study design and data analysis, applies mathematical models and clinical data to optimize the effect of drug treatments. Her research has spawned several recommendations for new dosing strategies that are implemented in the WHO's global guidelines. Recently, Professor Svensson was granted € 300,000 by the European EDCTP program to engage in two more international collaborations with a focus to identify additional tools to combat drug-resistant tuberculosis bacteria.

“In our upcoming projects, we will study the effects of a potential drug developed at Ludwig-Maximilians-Universität, and also test new combination treatments to map their effect on tuberculosis patients. We also hope to develop the healthcare infrastructure in a number of African countries, and the results we now present in The Lancet Infectious Diseases adds inspiration and prove the synergistic effects that arise when we tackle tuberculosis as a global community with the shared goal to make a difference for some of the world's most vulnerable patient groups,” states Elin Svensson.

Text: Magnus Alsne, photo: Mikael Wallerstedt a o