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.
RCT Entities:
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.
Authors: Lee Ann Jones; Lorna Doucette; Elisabeth P Dellon; Charles R Esther; Cameron J McKinzie Journal: J Cyst Fibros Date: 2019-05-03 Impact factor: 5.482
Authors: R G Masterton; A Galloway; G French; M Street; J Armstrong; E Brown; J Cleverley; P Dilworth; C Fry; A D Gascoigne; Alan Knox; Dilip Nathwani; Robert Spencer; Mark Wilcox Journal: J Antimicrob Chemother Date: 2008-04-29 Impact factor: 5.790