Optimizing Tedizolid Dosing in Cerebral Nocardiosis: Clinical Impact of Direct Unbound Concentration Measurement and Population PK Modelling in Two Cases

Abstract Introduction Tedizolid, a second-generation oxazolidinone, exhibits potent in vitro activity against Gram-positive bacteria, including Nocardia species, and has a more favourable safety profile than linezolid during prolonged use. However, data on itsCSF penetration and efficacy remain scarce. We describe two cases of Nocardia farcinica brain abscess treated with tedizolid and report measured serum and cerebrospinal fluid (CSF) exposures. Case reports Two patients with N. farcinica brain abscesses (MIC for tedizolid 0.75 mg/L) treated with tedizolid as part of combination therapy. Total and unbound concentrations in serum and CSF were quantified using LC-MS/MS, and PK/PD modelling was performed. In case 1, a 60-year-old man with idiopathic CD4 lymphocytopenia initially improved but relapsed while receiving tedizolid 200 mg once daily. The unbound plasma fraction was 15.7%, and CSF exposure remained low, with a predicted fAUC0–24/MIC