Tuberculosis (TB): Practice Essentials, Background, Pathophysiology
New TB Drugs Show Promise With Fewer Side Effects Than Linezolid
The drugs, sutezolid and delpazolid, have demonstrated strong antimicrobial activity and a notably better safety profile compared to linezolid, with potential to replace this current cornerstone in the treatment of drug-resistant TB. The findings were published on 7 July in two peer-reviewed articles in The Lancet Infectious Diseases, one of the world's leading journals in the field of infectious disease medicine. Research partners in Europe included Radboud university medical center from the Netherlands and the German Center for Infection Research (DZIF), Munich, the Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, the Center for International Health at LMU University Hospital and Helmholtz Munich.
The challenge with linezolidIn 2022, the World Health Organisation introduced lineozid as part of the BPaLM regimen, also comprising bedaquiline, pretomanid, and moxifloxacin, as the standard recommended 6-month treatment for patients with multidrug-resistant TB-reducing the duration from the previous standard 18 months. However, linezolid is problematic for patients as it shows significant toxicity. This prolonged exposure to linezolid, much longer than the originally intended use for bacterial skin infections, frequently leads to serious adverse events like anaemia or optical neuropathy, which are distressing for patients, may not resolve fully, and can require discontinuation of therapy, limiting treatment success.
Despite its effectiveness, linezolid is simply too toxic for many patients. We urgently need safer alternatives in this antibiotic class."
PD Dr. Norbert Heinrich
Both sutezolid and delpazolid are members of the oxazolidinone class, like linezolid, but are less toxic for patients. In two innovative Phase 2b clinical trials – SUDOCU (PanACEA Sutezolid Dose-finding and Combination Evaluation) and DECODE (PanACEA DElpazolid Dose-finding and COmbination DEvelopment) – both drugs were tested in combination with bedaquiline, delamanid, and moxifloxacin, making them the first trials to use these specific four-drug combinations. The studies, conducted in South Africa and Tanzania, showed that in patients with drug-sensitive pulmonary TB, both drugs are safer and more tolerable for patients than linezolid would be.
Key findings show better patient outcomesSutezolid was shown to be effective with strong antibacterial activity and was well tolerated across all tested doses, with no cases of nerve damage or blood toxicity-a critical advantage over linezolid. These results suggest sutezolid could be a safer alternative for future TB treatment regimens, particularly in long-term use, although no final dose recommendation can be made yet.
Delpazolid enhanced the effectiveness of the combination regimen with bedaquiline, delamanid, and moxifloxacin. A once-daily dose of 1200 mg achieved the desired drug levels for maximum efficacy and was well tolerated over 16 weeks. Importantly, no cases of nerve damage or blood-related side effects were observed at this dose. These results position delpazolid as a promising alternative to linezolid for future TB treatment regimens-pending confirmation in larger studies.
"These findings suggest that both drugs may offer safer treatment options for TB patients, particularly those requiring longer courses of therapy," – noted Dr Tina Minja, National PI for the DECODE study at NIMR-Mbeya Medical Research Centre in Tanzania.
A collaborative global effortThe studies were conducted as part of the PanACEA (Pan-African Consortium for the Evaluation of Anti-Tuberculosis Antibiotics) network, which includes clinical and academic partners across Africa and Europe. Both the SUDOCU and DECODE trials were innovative Phase 2b, open-label, randomized clinical studies that systematically compared different dosing levels to evaluate antibacterial activity, drug exposure, and safety profiles of sutezolid and delpazolid.
Looking aheadThe publication in The Lancet Infectious Diseases underscores the scientific relevance of these results and their potential to shape future TB treatment strategies. "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", commented Dr Ivan Norena, medical team lead at the Institute of Infectious Diseases and Tropical Medicine at LMU University Hospital Munich.
Further research is now planned to evaluate sutezolid and delpazolid in larger cohorts and in fully optimized treatment combinations. If the promising results are confirmed, these drugs could play a critical role in the next generation of TB therapies, helping to reduce treatment-related side effects while maintaining efficacy.
Elin Svensson, senior researcher from Radboud university medical center led the data analysis in both studies. She says: '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.'
Source:
Journal reference:
Minja, L. T., et al. (2025). Delpazolid in combination with bedaquiline, delamanid, and moxifloxacin for pulmonary tuberculosis (PanACEA-DECODE-01): a prospective, randomised, open-label, phase 2b, dose-finding trial. The Lancet Infectious Diseases. Doi.Org/10.1016/S1473-3099(25)00289-0.
Can More Rifampicin Speed Up TB Recovery Without Risks?
A higher dose of rifampicin might boost TB recovery—but does it carry risks? Tuberculosis (TB) may be curable, but it still kills over a million people each year. What if more of the key drug could help patients recover faster—and stay well longer? With rifampicin at the center of TB treatment for decades, scientists are now rethinking how we use it. Could a higher dose be the game-changer we've been waiting for?(1✔ ✔Trusted SourceEfficacy and safety of higher dose rifampicin in adults with presumed drug-susceptible tuberculosis: an updated systematic review and meta-analysisGo to source). 'Did You Know?TB still kills 1.3 million annually—but optimizing rifampicin doses may fast-track recovery and reduce community spread. #medindia #tuberculosis #rifampicin #clinicaltrials #infectiousdisease '
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Rifampicin: The Underdosed Hero? For years, 10 mg/kg of rifampicin has been the standard. But this number wasn't based on what works best—it was based on cost and caution. Now, this crucial drug might work better and faster at higher doses, potentially helping patients clear the infection more quickly.Advertisement
Faster Clearance = Lower Risk of Spread Early results show that doses between 20–30 mg/kg can lead to early sputum conversion—a key sign the infection is going away. This not only helps the patient recover but also reduces the risk of spreading TB in the community. That's a public health win, not just an individual one. Balancing Benefits and Risks While mid-range higher doses appear safe, going above 30 mg/kg may cause serious liver damage and other side effects. This raises an important message: More is not always better, and the right dose must strike a careful balance between speed and safety. What the Trials Actually Showed Across 19 trials and over 6,000 patients, evidence shows no clear benefit in survival or cure rates with doses above 15 mg/kg. But the trials mainly tested only modest increases. The need now is for stronger, longer studies that can test higher doses safely and track long-term relapse and survival outcomes.A Smarter, Safer Dose The real goal isn't just more medicine—it's better-targeted medicine. With support from the WHO and Wellcome Trust, researchers are now calling for larger, global trials to finally modernize TB treatment after 50 years of the same old approach.Reference:
Source-Indian Council of Medical Research (ICMR)
Two Novel Antibiotics Show Promise For TB Patients With Fewer Side ...
The drugs, sutezolid, and delpazolid, have demonstrated strong antimicrobial activity and a notably better safety profile compared to the currently used linezolid, with the potential to replace this current cornerstone in the treatment of drug-resistant TB
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Listen to this articleTwo novel antibiotics show promise for TB patients with fewer side effects: Lancet
xGerman researchers have developed two novel antibiotics that have shown promise for millions of patients with tuberculosis (TB), leading to lesser side effects than the currently available treatments.
The drugs, sutezolid, and delpazolid, have demonstrated strong antimicrobial activity and a notably better safety profile compared to the currently used linezolid, with the potential to replace this current cornerstone in the treatment of drug-resistant TB.
Two international clinical studies on the antibiotics published in two peer-reviewed articles in the journal The Lancet Infectious Diseases showed that both sutezolid and delpazolid are safe, effective, and potential alternatives to linezolid in the treatment of TB. "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," said Dr. Ivan Norena, medical team lead at the Institute of Infectious Diseases and Tropical Medicine at LMU University Hospital Munich. Linezolid was introduced by the World Health Organization (WHO) in 2022, as part of the BPaLM regimen, also comprising bedaquiline, pretomanid, and moxifloxacin, as the standard recommended 6-month treatment for patients with multidrug-resistant TB -- reducing the duration from the previous standard 18 months. However, linezolid was found to be problematic for patients as it showed significant toxicity. Prolonged exposure to linezolid, much longer than the originally intended use for bacterial skin infections, frequently leads to serious adverse events like anemia or optical neuropathy. "Despite its effectiveness, linezolid is simply too toxic for many patients. We urgently need safer alternatives in this antibiotic class," said PD Dr Norbert Heinrich, from the varsity. Both sutezolid and delpazolid are members of the oxazolidinone class, like linezolid, but are less toxic for patients. In the Phase 2b clinical trials, both drugs were tested in combination with bedaquiline, delamanid, and moxifloxacin, making them the first trials to use these specific four-drug combinations. The studies, conducted in South Africa and Tanzania, showed that in patients with drug-sensitive pulmonary TB, both drugs are safer and more tolerable for patients than linezolid would be. "These findings suggest that both drugs may offer safer treatment options for TB patients, particularly those requiring longer courses of therapy," said the researchers. This story has been sourced from a third party syndicated feed, agencies. Mid-day accepts no responsibility or liability for its dependability, trustworthiness, reliability and data of the text. Mid-day management/mid-day.Com reserves the sole right to alter, delete or remove (without notice) the content in its absolute discretion for any reason whatsoever.
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