JAC Advance Access originally published online on June 23, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(2):508-514; doi:10.1093/jac/dkh326
JAC vol.54 no.2 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.
Disposition of instilled versus nebulized tobramycin and imipenem in ventilated intensive care unit (ICU) patients
1 UVIR Institut Clínic de Pneumologia i Cirurgia Toràcica; 2 Servei de Farmàcia; 3 Laboratori de Farmacologia Clínica, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/Villarroel, 170, 08036 Barcelona, Spain
* Corresponding author. Tel: +34-93-227-54-79; Fax: +34-93-227-54-57; Email: dsoy{at}clinic.ub.es
Background: Delivery of antibiotics to the lower respiratory tract could potentially achieve antimicrobial bronchial drug concentrations without toxicity.
Aim: 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.
Keywords: administration, dosage , antibiotics , bronchial secretions , inhalation , intensive care , nosocomial pneumonia
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