Clinical trials identify safer alternatives to high-toxicity tuberculosis drug

Two investigational antibiotics have shown potential to replace linezolid in the treatment of drug-resistant tuberculosis (TB), offering a more tolerable safety profile and strong antimicrobial activity.

Both agents belong to the oxazolidinone class – like linezolid – but appear to reduce the risk of severe side effects. The studies formed part of the PanACEA – Pan-African Consortium for the Evaluation of Anti-Tuberculosis Antibiotics – network and the clinicl trials were undertaken in Tanzania and South Africa. European partners included Radboud University medical centre in the Netherlands, the German Centre for Infection Research (DZIF), Helmholtz Munich, the Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, and the Centre for International Health at LMU University Hospital, Munich.

The findings have been reported in The Lancet Infectious Diseases, following publication on 7 July of two peer-reviewed studies involving sutezolid and delpazolid.

In 2022, the World Health Organisation adopted linezolid as part of its six-month BPaLM regimen for multidrug-resistant TB which includes use of bedaquiline, pretomanid, linezolid and moxifloxacin. However, its toxicity profile has proven problematic, with many patients experiencing dose-limiting adverse effects such as anaemia and optic neuropathy.

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The SUDOCU and DECODE Phase 2b clinical trials have now tested sutezolid and delpazolid in novel four-drug regimens alongside BPaLM. The results indicated both alternatives were safer and more tolerable than linezolid in patients with drug-sensitive pulmonary TB.

Sutezolid demonstrated sustained antimicrobial activity across all tested doses, with no observed cases of blood toxicity or nerve damage. Delpazolid, meanwhile, reached therapeutic drug levels at a once-daily dose of 1,200 mg, with no associated nerve or blood-related side effects over a 16-week period.

“These findings suggest that both drugs may offer safer treatment options for TB patients, particularly those requiring longer courses of therapy,” said Dr Tina Minja, national principal investigator for the DECODE study at NIMR–Mbeya Medical Research Centre, Tanzania.

Dr Ivan Norena, medical team lead at LMU University Hospital, Munich, commented: “Seeing fewer side effects with sutezolid and delpazolid is a significant step forward – it brings us closer to TB therapies that are both effective and easier for patients to tolerate.”

Further trials have been planned to assess these agents in larger populations and fully optimised treatment regimens. If their advantages are confirmed, sutezolid and delpazolid could play a central role in future TB therapies, especially for individuals with drug-resistant forms of the disease.

Elin Svensson, senior researcher at Radboud university medical center, who led the data analysis, said: “These findings are encouraging and show there is hope for better drugs for drug-resistant TB. Without the collaboration within PanACEA, this would not have been possible in such a short time. It highlights the importance of tackling TB as a global community.”