Published ahead of print on October 11, 2002, doi:10.1164/rccm.200204-363OC Am. J. Respir. Crit. Care Med., Volume 166, Number 10, November 2002, 1375-1381 A more recent version of this article appeared on November 15, 2002
Submitted on April 24, 2002 Lung Deposition and Efficiency of Nebulized Amikacin during E. coli Pneumonia in Ventilated PigletsIvan Goldstein1,1 Department of Anesthesiology, La Pitie-Salpetriere Hospital, Paris, France, 2 Department of Bacteriology, La Pitie-Salpetriere Hospital, Paris, France, 3 DHURE and INSERM U 416, University of Medicine, Lille, France * To whom correspondence should be addressed. E-mail: jjrouby.pitie{at}invivo.edu.
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 hrs following the inoculation, either through an ultrasonic nebulizer (45 mg/kg, n=10) or by intravenous infusion (15 mg/kg, n=8). Piglets were sacrificed 1 hour after a second AMK administration performed 24 hrs 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 in lung segments with mild bronchopneumonia versus 40 ± 65 µg/g 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 cfu/g vs median = 5.102 cfu/g, p < 0.001). In conclusion, the deposition of AMK in infected lung parenchyma and the efficiency of bacterial killing were greater after nebulization than following intravenous administration. Key words: aerosol,aminoglycosides,piglets,bronchopneumonia, mechanical ventilation
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