Two international clinical studies led by the Tropical Institute of the LMU Klinikum München and partner institutions have demonstrated the safety and efficacy of the antibiotics sutezolid and delpazolid as alternatives to linezolid in the treatment of multidrug-resistant tuberculosis. The active substances showed strong antimicrobial activity and better tolerability. The results were published on July 8 in two articles in the journal The Lancet Infectious Diseases. The German partners were the German Center for Infection Research in Munich, the Fraunhofer Institute for Translational Medicine and Pharmacology, the Center for International Health at the LMU Klinikum and Helmholtz Munich.

Since 2022, linezolid has been part of the BPaLM regimen recommended by the World Health Organization for the six-month treatment of multidrug-resistant tuberculosis, together with bedaquiline, pretomanid and moxifloxacin. The shortening of the treatment duration from 18 months was a step forward, but linezolid often causes severe side effects such as anemia or optic neuropathy, which can be permanent and force treatment discontinuation.

Sutezolid and delpazolid, both from the oxazolidinone class, have lower toxicity. In the Phase IIb studies SUDOCU and DECODE, they were combined for the first time with bedaquiline, delamanid and moxifloxacin and tested in patients with drug-sensitive pulmonary tuberculosis in South Africa and Tanzania. Both active substances proved to be better tolerated.

Sutezolid demonstrated antibacterial activity across all doses without neuropathy or hematologic toxicity, making it suitable for prolonged use, although a final dosing recommendation is pending. Delpazolid increased the efficacy of the combination at a daily dose of 1200 milligrams for 16 weeks, achieved optimal drug levels and caused no nerve damage or hematotoxic effects.

The studies conducted as part of the Pan-African Consortium for the Evaluation of Anti-Tuberculosis Antibiotics compared doses in terms of activity, exposure and safety. The results indicate safer options for tuberculosis patients, especially for longer therapies.

Further studies with larger groups and optimized combinations are planned. If confirmed, the active substances could play a key role in future therapies.

The SUDOCU study was funded by the EDCTP2 program of the European Union, the German Federal Ministry of Education and Research and the Netherlands Organization for Scientific Research, supplemented by the German Center for Infection Research. Otsuka provided Delamanid free of charge, Sequella supplied Sutezolid. The DECODE study was funded by LigaChem Biosciences using PanACEA structures, with free delamanid from Otsuka.

Original Papers:

Delpazolid in combination with bedaquiline, delamanid, and moxifloxacin for pulmonary tuberculosis (PanACEA-DECODE-01): a prospective, randomized, open-label, phase 2b, dose-finding trial – The Lancet Infectious Diseases

Sutezolid in combination with bedaquiline, delamanid, and moxifloxacin for pulmonary tuberculosis (PanACEA-SUDOCU-01): a prospective, open-label, randomized, phase 2b dose-finding trial – The Lancet Infectious Diseases

The patient pursuit of safe treatment options for tuberculosis – The Lancet Infectious Diseases

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