The aim of this study was to investigate the pharmacokinetic/pharmacodynamic parameters of linezolid in both the plasma and epithelial lining fluid (ELF) of patients with pneumonia-induced sepsis. Blood specimens and bronchoalveolar lavage samples were collected at defined time points after administration of linezolid. The concentration in the ELF was calculated by urea dilution method. PK parameters were calculated, and probability of target attainment was evaluated by Monte Carlo simulations. Twenty-three patients were enrolled, 8 of whom had septic shock. The maximum concentration of linezolid was higher in the ELF than in the plasma (36.02 ± 13.17 vs 19.51±4.83 mg/L, P < .001) in all of the patients. In patients with septic shock, the maximum concentration in the ELF was significantly higher than that in the non-septic shock group (45.25 ± 11.70 vs 31.10 ± 11.38 mg/L, P = .01), while there was no significant difference in the plasma. The corresponding probability of target attainment values were 90.5% and 65.1% in ELF and plasma, respectively, with a minimum inhibitory concentration of 2 mg/L, which were 99.9% in the ELF in the patients with septic shock. Linezolid possesses an efficient penetration into the ELF of patients with pneumonia-induced sepsis with mechanical ventilation. When minimum inhibitory concentration ≤ 2 mg/L, 600 mg of linezolid every 12 hours could achieve the optimal therapeutic targets in the ELF rather than in the plasma of patients with pneumonia-induced sepsis.
Keywords: critically ill; epithelial lining fluid; linezolid; pharmacokinetics; septic shock.
© 2022, The American College of Clinical Pharmacology.