Disposition of instilled versus nebulized tobramycin and imipenem in ventilated intensive care unit (ICU) patients.

Author(s): Badia JR, Soy D, Adrover M, Ferrer M, Sarasa M, Alarcon A, Codina C, Torres A

Affiliation(s): UVIR Institut Clinic de Pneumologia i Cirurgia Toracica, Barcelona, Spain.

Publication date & source: 2004-08, J Antimicrob Chemother., 54(2):508-14. Epub 2004 Jun 23.

Publication type: Clinical Trial; Randomized Controlled Trial

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.