Penetration of linezolid into the pleural cavity in critically ill patients with proven or suspected Gram-positive bacterial infections: a retrospective pharmacokinetic study

Objectives: To describe the pharmacokinetics (PK) of linezolid in plasma and pleural fluid (PF) in critically ill patients with proven or suspected Gram-positive bacterial infections.

Patients and methods: Observational PK study in 14 critically ill patients treated with linezolid at standard doses. Blood and PF samples were collected and analysed by HPLC. The ratio between PF and plasma concentrations was calculated. The PK/pharmacodynamic (PD) target of linezolid in plasma was defined as 100% of the duration of the dosing interval in which concentrations were above the MIC (%100 T > MIC).

Results: The median (5th and 95th percentiles) linezolid concentration values for plasma pre-dose at steady state (Cmin,ss) and at the end of the 1-h infusion at steady state (Cmax,ss) were 1.1 (0.02-28.3) and 13.8 mg/L (2.9-38.1), respectively, and the PF pre-dose concentration (PF0 h) and PF concentration at the end of the 1-h intravenous infusion (PF1 h) were 2.8 (0.1-31.6) and 4.2 mg/L (0.1-45.2), respectively. At both times (pre-dose and post-infusion), a strong positive correlation was observed between PF and plasma linezolid concentrations (Spearman's rho coefficients = 0.8 and 0.9, with P < 0.001 for both). The defined PK/PD target in plasma was achieved in 8 (57.1%), 4 (28.6%) and 3 (21.4%) patients assuming an MIC of 1, 2 and 4 mg/L, respectively.

Conclusions: Linezolid seems to penetrate well into the PF, with concentrations exceeding those in plasma. However, high inter-individual variability, both in plasma and PF concentrations, was observed. A high proportion of patients did not achieve the PK/PD target in plasma, especially in the presence of high MIC strains.