From linezolid to contezolid: a strategy for safe continuation of therapy in complex tuberculosis

Background: Linezolid (Lzd) is a cornerstone for drug-resistant and complex tuberculosis (TB), but its utility is severely limited by hematological and neurological toxicities. Contezolid (Czd), a novel oxazolidinone, offers a potentially safer profile. However, real-world evidence remains limited. Objective: To evaluate the real-world effectiveness and safety of Czd in patients with complex TB, focusing on its role in managing Lzd toxicity through two distinct strategies: salvage therapy for Lzd-intolerant patients and proactive initiation in patients at high risk for Lzd-related adverse events. Methods: We conducted a retrospective study of TB patients treated with Czd-containing regimens. Patients were categorized into two groups: Group A switched from Lzd to Czd due to Lzd intolerance; Group B received Czd as initial treatment due to high risk of Lzd toxicity. Treatment outcomes, adverse events (AEs), and resolution of Lzd-related AEs after switching to Czd were analyzed. Results: All 31 patients in Group A experienced Lzd-related AEs (100%), with median onset of 45 days. Anemia was the most common AE (90%). After switching to Czd, significant recovery occurred in all AEs, with 52% achieving complete AE resolution. In Group B, no significant changes were observed. Treatment outcomes were excellent in both groups, with 100% clinical improvement and high sputum culture conversion rates (90% vs. 88%). Conclusion: Czd represented an effective salvage strategy for Lzd intolerance, significantly improving toxicity, ensuring therapeutic continuity, and suggesting preliminary evidence of maintained efficacy in complex TB. For patients at high risk of Lzd-related AEs, selecting Czd as initial therapy may prevent severe toxicity.