Comparative Effectiveness and Hematological Safety of Linezolid and Tedizolid in Bone and Joint Infections: A Retrospective Cohort Study

INTRODUCTION: Tedizolid is a promising alternative to linezolid for bone and joint infections (BJIs), but real-world comparative data remain scarce. We aimed to assess the effectiveness and hematological safety of tedizolid versus linezolid in this setting. METHODS: We conducted a retrospective, single-center observational study at Nimes University Hospital, a French BJIs reference center, including adults treated with linezolid or tedizolid for BJI between December 2018 and September 2023. The primary endpoint was a composite of clinical failure at end of treatment, relapse within 60 days, all-cause 1-year mortality, or antibiotic discontinuation due to adverse events. Secondary endpoints included each component separately and hematological trajectories. Inverse probability of treatment weighting was applied to adjust for confounders. RESULTS: A total of 202 patients were analyzed (147 linezolid; 55 tedizolid, including 38 switched from linezolid). Staphylococcus spp. accounted for 71% of cases, and 50.5% of infections were polymicrobial. The composite endpoint occurred in 38% of patients on linezolid and 22% on tedizolid (p = 0.04). In propensity-weighted analysis, tedizolid was non-inferior to linezolid (risk difference - 5.6%, 95% CI - 24.2-13.0%). Hematological tolerance favored tedizolid: adjusted hemoglobin and platelet count variations were significantly higher at day 28 (Δ hemoglobin + 1.09 g/dL, 0.54-1.65; p < 0.001; Δ platelets + 134.1 G/L, 92.0-176.3; p < 0.001). CONCLUSIONS: Tedizolid was non-inferior to linezolid for the treatment of BJIs and was associated with improved hematological safety. These findings support the use of tedizolid as a valuable alternative in complex BJIs, particularly in patients at risk of cytopenia.