Contezolid in tuberculous meningitis: comparable efficacy and favorable safety

Tuberculous meningitis (TBM) is the most severe and fatal form of tuberculosis (TB). Linezolid (Lzd), a key oxazolidinone with excellent central nervous system penetration, is widely used for TBM but is limited by significant adverse events (AEs). Contezolid (Czd), a next-generation oxazolidinone structurally optimized from Lzd, has shown promising potential. However, clinical evidence for its use in TBM remains limited to isolated case reports.

We conducted a retrospective study of TBM patients treated with Czd- or Lzd-containing regimens. Patients were categorized into two groups: the Czd group (n=16, including 9 patients who switched from Lzd to Czd due to Lzd intolerance) and the Lzd group (n=32). We analyzed treatment outcomes, including Cerebrospinal fluid (CSF) parameters, imaging findings, and CSF culture conversion, as well as safety outcomes in both groups.

No AEs were observed in the Czd group, and hematological parameters remained stable. All Lzd-related AEs completely resolved after switching to Czd in the Lzd-to-Czd group. In the Lzd group, 68.75% experienced AEs, with 34.38% requiring dose reduction and 21.88% discontinuing treatment. Treatment outcomes were favorable in both groups: all 48 patients achieved clinical symptom improvement, with CSF Mtb culture conversion rates of 100% (Czd) vs. 93.33% (Lzd), and radiological improvement in 81.25% of patients in both groups. No significant differences were found in CSF parameter trends between the two groups (all P > 0.05).

Czd represents an effective salvage strategy for Lzd intolerance and may prevent severe AEs while maintaining efficacy comparable to Lzd. These findings support Czd as a valuable alternative for TBM treatment.