Background and Importance Sepsis-induced pathophysiological changes can result in serious alterations in the pharmacokinetic parameters of antibiotics. Drug exposure is consequently difficult to predict in critically ill septic patients. The latest Surviving Sepsis Campaign guidelines recommend routine therapeutic drug monitoring (TDM) to optimise antibiotic therapy in this patient population. Linezolid is an oxazolidinone antibiotic used to treat infections caused by gram-positive bacteria. The prevalence of its adverse effects is associated with higher exposure, while suboptimal concentrations can lead to treatment failure and an increased risk of clonal evolution of resistant strains.

Aim and Objectives Our aim was to determine optimal dosing strategies among critically ill septic patients after high-risk cardiovascular surgery treated at the intensive care units of a national cardiovascular surgery centre based on TDM results.

Materials and Methods We retrospectively analysed the data of patients treated at our centre from April 2022 to August 2023. A total of 15 patients (11 men, four women) receiving empiric or targeted linezolid therapy guided by TDM were included. Blood samples were centrifuged immediately after being collected, and serum linezolid levels were measured within 24 hours. Trough levels were evaluated when using an intermittent dosing regimen, while blood was taken at random times after reaching the steady state when a continuous infusion was applied.

Results Dose adjustments were performed in 11 patients based on TDM results. Optimal linezolid exposure was only achieved when higher doses (1800–2400 mg/24h) were administered by continuous infusion. This regimen, which was subsequently introduced into routine care, led to linezolid overexposure in a single patient. Dose reduction with clinical improvement was accomplished in three patients. Serum linezolid levels showed no correlation with kidney function, age, or gender.

Conclusion and Relevance Optimal linezolid exposure often cannot be achieved with standard dosing regimens in critically ill patients after high-risk cardiovascular surgery. Higher doses and continuous infusion regimes may be required in this population. TDM is an important tool for guiding therapy.