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

• Published in: American journal of respiratory and critical care medicine 2002-11, Vol.166 (10), p.1375-1381
• Main Authors: Goldstein, Ivan, Wallet, Frederic, Nicolas-Robin, Armelle, Ferrari, Fabio, Marquette, Charles-Hugo, Rouby, Jean-Jacques
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Amikacin - metabolism; Amikacin - pharmacokinetics; Amikacin - therapeutic use; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - therapeutic use; Biological and medical sciences; Bronchopneumonia - drug therapy; Bronchopneumonia - metabolism; Bronchopneumonia - microbiology; Disease Models, Animal; Dose-Response Relationship, Drug; Emergency and intensive respiratory care; Escherichia coli Infections - drug therapy; Escherichia coli Infections - metabolism; Escherichia coli Infections - microbiology; Injections, Intravenous; Intensive care medicine; Lung - drug effects; Lung - microbiology; Lung - pathology; Medical sciences; Nebulizers and Vaporizers; Pneumonia, Bacterial - drug therapy; Pneumonia, Bacterial - metabolism; Pneumonia, Bacterial - microbiology; Respiration, Artificial; Severity of Illness Index; Swine; Treatment Outcome
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200204-363OC

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 x kg-1, n = 10) or by intravenous infusion (15 mg x 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 microg x g-1 in lung segments with mild bronchopneumonia versus 40 +/- 65 microg x 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 x 10(2) colony forming units x 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.