Am. J. Respir. Crit. Care Med., Volume 165, Number 2, January 2002, 171-175

Lung Tissue Concentrations of Nebulized Amikacin during Mechanical Ventilation in Piglets with Healthy Lungs

IVAN GOLDSTEIN, FREDERIC WALLET, JEROME ROBERT, MARIE-HELENE BECQUEMIN, CHARLES-HUGO MARQUETTE, JEAN-JACQUES ROUBY, and the Experimental ICU Study Group

Pierre Viars Surgical Intensive Care Unit, Department of Anesthesiology, Department of Bacteriology, and Service des Explorations Fonctionnelles Respiratoires et UPRES ² 397, Pitié-Salpêtrière Hospital, University of Paris VI, Paris; Department of Bacteriology, DHURE, and INSERM U 416, University of Medicine, Lille, France

The tissue concentration of aminoglycosides in lung parenchyma is the main determinant of bactericidal efficiency. The aim of the study was to compare the lung deposition of amikacin administered either by an ultrasonic nebulizer or by intravenous infusion during mechanical ventilation. Eighteen healthy ventilated piglets received a single daily dose of amikacin by intravenous infusion (15 mg · kg¹) and 18 by aerosol (1 g in 12 ml). The amount of aerosolized amikacin reaching the tracheobronchial tree represented 40 ± 5% of the initial dose with an aerodynamic size distribution showing 50% of particles ranging between 0.5 and 5 µm mass median diameter. Animals were killed at different time intervals after the second dose. Tissue concentrations of amikacin were determined on cryomixed multiple lung specimen by an immunoenzymatic method. The lung concentrations of nebulized amikacin, peaking at 208 ± 76 µg · g¹, were more than 10-fold higher than the lung concentrations of intravenous amikacin and were homogeneously distributed throughout the lung parenchyma. Amikacin plasma concentrations lower than 5 mmol · l¹ were measured after the sixth hour after the nebulization. In conclusion, the ultrasonic nebulization of amikacin resulted in high tissue concentrations, far above the minimal inhibitory concentrations of most gram-negative strains.

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