title: Disposition of instilled versus nebulized tobramycin and imipenem in ventilated intensive care unit (ICU) patients.
abstract: BACKGROUND
  Delivery of antibiotics to the lower respiratory tract could potentially achieve antimicrobial bronchial drug concentrations without toxicity.
  
  
  OBJECTIVE
  To assess bronchial and serum concentrations of imipenem or tobramycin obtained by nebulization or instillation in critically ill mechanically ventilated patients.
  
  
  METHODS
  Prospective randomized open trial. Eighteen patients ventilated for more than 48 h were included. Two doses of imipenem/cilastatin (1000/500 mg) separated by 8 h, or two doses of tobramycin 200 mg separated by 12 h were randomly nebulized or instilled into the tracheal tube. Five bronchoaspirates (two bronchoscopic, three blind) and five blood samples were collected on a timed schedule after the second dose. Respiratory and serum samples were analysed by HPLC, and a subset of blood samples was also evaluated by enzyme-immunoassay.
  
  
  RESULTS
  When instilled, imipenem/cilastatin obtained higher concentrations in respiratory secretions than when nebulized (P=0.022, 1 h after the last dose; P=0.029, 2 h after the last dose). Tobramycin showed equally high concentrations when nebulized or instilled. Instillation of tobramycin may result in significant accumulation in patients with renal failure.
  
  
  CONCLUSIONS
  High bronchial concentrations of imipenem could only be achieved by instillation, whereas tobramycin seems suitable for both modes of administration. Instillation of these antibiotics is a safe procedure that achieves high drug concentrations in respiratory secretions.
authors.affiliation: UVIR Institut Clínic de Pneumologia i Cirurgia Toràcica, Barcelona, Spain.
authors.forename: Joan R
authors.initials: JR
authors.lastname: Badia
authors.forename: Dolors
authors.initials: D
authors.lastname: Soy
authors.forename: Maria
authors.initials: M
authors.lastname: Adrover
authors.forename: Miquel
authors.initials: M
authors.lastname: Ferrer
authors.forename: Maria
authors.initials: M
authors.lastname: Sarasa
authors.forename: Antonio
authors.initials: A
authors.lastname: Alarcón
authors.forename: Carles
authors.initials: C
authors.lastname: Codina
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001980:Bronchi / Q000382:microbiology; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D002985:Clinical Protocols; D003422:Critical Care; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011446:Prospective Studies; D012121:Respiration, Artificial; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology; D013056:Spectrophotometry, Ultraviolet; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem; D014031:Tobramycin