JAC Advance Access published online on June 23, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh326
© 2004 by The British Society for Antimicrobial Chemotherapy
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1 UVIR Institut Clínic de Pneumologia i Cirurgia Toràcica, Barcelona, Spain
* To whom correspondence should be addressed. E-mail: 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.
Revised April 26, 2004
Accepted May 15, 2004
Original article
Disposition of instilled versus nebulized tobramycin and imipenem in ventilated intensive care unit (ICU) patients
2 Servei de Farmàcia, Barcelona, Spain
3 Laboratori de Farmacologia Clínica, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/Villarroel, 170, 08036 Barcelona, Spain
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