LINEZOLID, a staple in drug-resistant tuberculosis (TB) treatment, is known for its efficacy but also its dose-limiting toxicities, especially haematologic and neurologic side effects. In response, two recent studies evaluated novel oxazolidinones, delpazolid and sutezolid, to identify safer, effective alternatives. Both were tested in combination with the new standard background regimen of bedaquiline, delamanid, and moxifloxacin, offering encouraging results.
Delpazolid (PanACEA-DECODE-01)1
A Phase 2b, randomised, open-label trial conducted across sites in Tanzania and South Africa enrolled 76 adults with newly diagnosed, smear-positive pulmonary TB. Participants were randomised into five arms receiving 0–1,600 mg/day of oral delpazolid for 16 weeks alongside bedaquiline, delamanid, and moxifloxacin. The primary endpoint was change in mycobacterial load; safety focused on oxazolidinone class toxicities.
Pharmacokinetic–pharmacodynamic modelling showed maximal efficacy at a daily exposure (AUC0-24) of 50 mg/L per hour, achieved with a median 1,200 mg daily dose. Delpazolid contributed to a 38% faster bacterial clearance compared to the control group (p=0.025). No significant differences were observed in time to sustained culture conversion between arms, though pooled delpazolid groups showed a non-significant trend toward improvement (hazard ratio: 1.53). Importantly, no classic oxazolidinone class toxicities were observed, suggesting a favourable safety profile.
Sutezolid (PanACEA-SUDOCU-01)2
This Phase 2b open-label trial enrolled 75 adults across four African sites, randomised into five arms receiving 0–1,600 mg/day of sutezolid for 12 weeks plus the same background regimen. Weekly sputum sampling assessed efficacy, and comprehensive safety monitoring included ECGs and blood tests.
Sutezolid led to a 16.7% improvement in bacterial clearance rate compared to no sutezolid (p<0.05), with no clear maximum effect observed across the tested doses. Notably, no oxazolidinone class toxicities or neuropathies were reported. QT prolongation (>60 ms) occurred in 8% of participants but was not dose-dependent or deemed clinically significant. Only two Grade 4 adverse events occurred, neither attributed to sutezolid.
Both delpazolid and sutezolid demonstrated added bactericidal activity and a notably improved safety profile over linezolid, particularly regarding neuropathy and haematologic toxicity. Delpazolid showed maximal effect at 1,200 mg/day, while sutezolid’s optimal dose remains to be refined. These findings support continued clinical development of both agents as viable, safer oxazolidinones for future TB regimens.
References
- Minja LT et al. Delpazolid in combination with bedaquiline, delamanid, and moxifloxacin for pulmonary tuberculosis (PanACEA-DECODE-01): a prospective, randomised, open-label, phase 2b, dose-finding trial. Lancet Infect Dis. 2025; DOI: 10.1016/S1473-3099(25)00289-0.
- Heinrich N et al. Sutezolid in combination with bedaquiline, delamanid, and moxifloxacin for pulmonary tuberculosis (PanACEA-SUDOCU-01): a prospective, open-label, randomised, phase 2b dose-finding trial. Lancet Infect Dis. 2025; DOI: 10.1016/S1473-3099(25)00213-0.
