Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator-associated pneumonia
We conducted a prospective, open-label study to determine the steady-state serum and epithelial lining fluid (ELF) concentrations of unbound ertapenem administered once daily to critically ill patients with early-onset ventilator-associated pneumonia (VAP).
Design and setting
Prospective, open-label study in an intensive care unit and research ward in a university hospital.
Fifteen patients with VAP received 1-h intravenous infusions of 1 g ertapenem once daily.
After 2 days of therapy the steady-state serum and ELF concentrations of free ertapenem were determined by high-performance liquid chromatography.
Measurements and results
The median (interquartile range) free ertapenem peak (Cmax), intermediate (C12), and trough (Cmin) concentrations (mg/l) 1, 12, and 24 h after the end of infusion were 30.3 (27.1–37.8), 4.8 (3.9–6.4), and 0.8 (0.5–1.2) in serum and 9.4 (8.0–10.7), 2.0 (1.1–2.5), and 0.3 (0.2–0.4) in ELF, respectively, showing a median free ertapenem percentage penetration in ELF of approx. 30%. The median (interquartile range) serum area under concentration-time curve of free ertapenem during the observational period was 226.7 mg h−1 l−1 (202.2–263.9).
Our study shows satisfactory results, with unbound ertapenem concentrations both in serum and ELF exceeding the MIC90 values of most of the causative pathogens encountered in early-onset VAP during 50–100% time. This suggests that 1 g intravenous ertapenem administered once daily should be effective during the treatment of early-onset VAP in critically ill patients with no known risk factors for multidrug-resistant pathogens.
KeywordsErtapenem Pharmacokinetics Lung diffusion Intensive care Early-onset Ventilator-associated pneumonia
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