Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator-associated pneumonia

Objective: 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. Patients: Fifteen patients with VAP received 1-h intravenous infusions of 1 g ertapenem once daily. Interventions: 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 (C-max), intermediate (C-12), and trough (C-min) 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). Conclusion: 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.