Therapeutic drug monitoring and target attainment of unbound flucloxacillin in hospitalized patients with measured MICs (FLUTE)

Objectives To determine the proportion of patients achieving target attainment of unbound flucloxacillin in blood plasma, evaluate the association between unbound flucloxacillin concentration and toxicity and identify patient subgroups that may benefit from therapeutic drug monitoring (TDM) of unbound flucloxacillin. Patients and methods A single-centre retrospective observational study was performed of patients admitted to the Meander Medical Centre between 1 July 2023 and 30 June 2024 who were treated with flucloxacillin and had an unbound flucloxacillin concentration measured ≥48 h after initiation of flucloxacillin treatment. Target attainment was defined as an unbound flucloxacillin concentration within 4–10× the measured MIC (0.25 mg/L in the absence of a positive culture). Results For the first measured plasma sample (n = 203), target attainment was achieved in 33% of patients, 35% fell below the target range and 32% exceeded the target range. Threshold concentrations for unbound flucloxacillin were 10.0 mg/L for nephrotoxicity and 21.0 mg/L for neurotoxicity. Above these concentrations, 66.7% and 46.2% of patients developed nephrotoxicity and neurotoxicity, respectively. An unbound flucloxacillin concentration >10 mg/L was observed in 23 (11.3%) patients, 21 of whom had an glomerular filtration rate <50 mL/min/1.73 m2. Conclusions Target attainment of unbound flucloxacillin was achieved in one third of patients, while a substantial number of patients had an unbound flucloxacillin concentration >10 mg/L, which was associated with increased toxicity. We advise routine TDM of unbound flucloxacillin for patients with impaired renal function and a high daily dose to mitigate the risk of flucloxacillin-associated nephrotoxicity and neurotoxicity.