title: Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator-associated pneumonia.
abstract: 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).
  
  
  METHODS
  Prospective, open-label study in an intensive care unit and research ward in a university hospital.
  
  
  METHODS
  Fifteen patients with VAP received 1-h intravenous infusions of 1 g ertapenem once daily.
  
  
  METHODS
  After 2 days of therapy the steady-state serum and ELF concentrations of free ertapenem were determined by high-performance liquid chromatography.
  
  
  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).
  
  
  CONCLUSIONS
  Our study shows satisfactory results, with unbound ertapenem concentrations both in serum and ELF exceeding the MIC(90) 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.
authors.affiliation: Claude Bernard University, Avenue Rockefeller, Lyon, France. emmanuel.boselli@chu-lyon.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Boselli
authors.forename: Dominique
authors.initials: D
authors.lastname: Breilh
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Saux
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Gordien
authors.forename: Bernard
authors.initials: B
authors.lastname: Allaouchiche
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D000077727:Ertapenem; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000378:metabolism*; D047090:beta-Lactams / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077727:Ertapenem