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Published ahead of print on October 11, 2002, doi:10.1164/rccm.200204-363OC
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American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 1375-1381, (2002)
© 2002 American Thoracic Society

Original Article

Lung Deposition and Efficiency of Nebulized Amikacin during Escherichia coli Pneumonia in Ventilated Piglets

Ivan Goldstein, Frederic Wallet, Armelle Nicolas-Robin, Fabio Ferrari, Charles-Hugo Marquette and Jean-Jacques Rouby and the Experimental Intensive Care Unit Study Group

Réanimation Chirurgicale Pierre Viars, Department of Anesthesiology, Pitié-Salpêtrière Hospital, University of Paris VI, Paris; and Department of Bacteriology, DHURE and INSERM U 416, University of Medicine, Lille, France

Correspondence and requests for reprints should be addressed to Jean-Jaques Rouby, Réanimation Chirurgicale Pierre Viars, Department of Anesthesiology, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France. E-mail: jjrouby.pitie{at}invivo.edu or jean-jacques.rouby{at}psl.ap-hop-paris.fr

Lung tissue deposition and antibacterial efficiency of nebulized and intravenous amikacin (AMK) were compared in anesthetized and ventilated piglets suffering from a bronchopneumonia produced by the intrabronchial inoculation of Escherichia coli. AMK was administered 24 hours after the inoculation either through an ultrasonic nebulizer (45 mg · kg-1, n = 10) or by intravenous infusion (15 mg · kg-1, n = 8). Piglets were killed 1 hour after a second AMK administration performed 24 hours after the first one, and lung tissue concentrations of AMK and lung bacterial burden were assessed on multiple lung specimens. The amount of nebulized AMK reaching the tracheobronchial tree represented 38 ± 6% of the initial nebulizer AMK charge. After nebulization, AMK lung tissue concentrations were 3- to 30-fold higher than after intravenous administration and were influenced by the severity of lung lesions: 188 ± 175 µg · g-1 in lung segments with mild bronchopneumonia versus 40 ± 65 µg · g-1 in lung segments with severe bronchopneumonia (p < 0.01). Lung bacterial burden was significantly lower in the aerosol group than in the intravenous group (median = 0 colony forming units · g-1 versus median = 5 · 102 colony forming units · g-1, p < 0.001). In conclusion, the deposition of AMK in infected lung parenchyma and the efficiency of bacterial killing were greater after nebulization than after intravenous administration.

Key Words: aerosols • aminoglycosides • piglets • bronchopneumonia • mechanical ventilation




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