Realising safer tuberculosis treatment with novel antibiotics

New research has found two novel antibiotics that could provide safer treatment options for drug-resistant tuberculosis.

Sutezolid and delpazolid are part of a class of medicines called oxazolidinones. When compared to linezolid, these drugs have demonstrated strong antimicrobial activity and an improved safety profile.

Linezolid was introduced as part of the BPaLM regimen (bedaquiline, pretomanid, and moxifloxacin) in 2022. The World Health Organisation (WHO) recommended it as a standard six-month treatment for multidrug-resistant tuberculosis, the researchers highlighted.

However, ”despite its effectiveness, linezolid is simply too toxic for many patients. We urgently need safer alternatives in this antibiotic class,” stated PD Dr Norbert Heinrich, Institute of Infectious Diseases and Tropical Medicine, LMU University Hospital Munich.

Working to improve outcomes in tuberculosis – potential of the novel antibiotics

Two Phase IIb clinical trials evaluated sutezolid and delpazolid in combination with bedaquiline, delamanid, and moxifloxacin, making them the first trials to use these specific four-drug combinations. In patients with drug-sensitive pulmonary tuberculosis, the antibiotics were reportedly safer and more tolerable compared to linezolid.

Specifically, sutezolid demonstrated strong antibacterial activity and was well tolerated across all tested doses. On the other hand, delpazolid improved the effectiveness of the combination therapy with bedaquiline, delamanid, and moxifloxacin. A once-daily 1200mg dose achieved the desired drug levels for maximum efficacy. This was well tolerated over a 16-week period, the team shared.

“These findings suggest that both drugs may offer safer treatment options for [tuberculosis] patients, particularly those requiring longer courses of therapy,” explained Dr Tina Minja, National PI for the DECODE study at NIMR-Mbeya Medical Research Centre in Tanzania.

Future tuberculosis treatment landscape

“Seeing fewer side effects with sutezolid and delpazolid is a significant step forward—it brings us closer to [tuberculosis] therapies that are both effective and easier for patients to tolerate,” commented Dr Ivan Norena, Medical Team Lead at the Institute of Infectious Diseases and Tropical Medicine at LMU University Hospital Munich.

Going forward, the research team plan to evaluate sutezolid and delpazolid in larger cohorts. Notably, subject to further development of these drugs as a new treatment for drug-resistant tuberculosis, the antibiotics could play a key role in reducing treatment-related side effects while maintaining efficacy as next generation medicines for the disease.

These new findings were published in two peer-reviewed articles in The Lancet Infectious Diseases.