[Achievement of pharmacokinetic/pharmacodynamic targets with linezolid therapeutic drug monitoring in critically ill patients].

BACKGROUND

Standard dosing of linezolid regimen frequently results in suboptimal exposure in critically ill patients. This study aimed to analyze the association between dosing regimens (total daily dose and infusion duration) and the probability of achieving pharmacokinetic/pharmacodynamic targets, as well as their microbiological and clinical impact.

METHODS

A retrospective observational study was conducted in critically ill patients admitted to intensive care units who underwent therapeutic drug monitoring of linezolid between May 2021 and December 2023. Achievement of pharmacokinetic/pharmacodynamic targets (Cmin: 2-7 mg/L, AUC: 0-24/MIC: 80-120 mg*h/L, and T>MIC =85%) was evaluated according to the initial regimens (1,200 or 1,800 mg/day) and infusion duration (1 or 3 hours). Risk subgroups included obesity, augmented creatinine clearance, renal replacement therapy, and age <65 years.

RESULTS

Seventy patients were included. At the first monitoring, only 18.6% achieved all three pharmacokinetic/pharmacodynamic targets and 40% achieved the Cmin target. No statistically significant differences were observed in target attainment according to dose or infusion duration, including within risk subgroups. However, the 1,800 mg/day regime showed a numerically higher proportion of patients achieving the Cmin target (54.5% vs. 37.3%). No significant differences in microbiological or clinical outcomes were observed between patients with Cmin within the target range and those outside it.

CONCLUSIONS

Fewer than 20% of critically ill patients achieve all pharmacokinetic/pharmacodynamic targets with the initial regimen. These findings support the need for individualized dosing and therapeutic drug monitoring to optimize linezolid treatment in this population, particularly in high-risk patients.