Lung tissue concentrations of nebulized amikacin during mechanical ventilation in piglets with healthy lungs.
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. kg(-1)) 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 microm 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 microg. g(-1), 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. l(-1) 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.
Goldstein
Ivan
I
Pierre Viars Surgical Intensive Care Unit, Department of Anesthesiology, Service des Explorations Fonctionnelles Respiratoires et UPRES, France.
Wallet
Frederic
F
Robert
Jerome
J
Becquemin
Marie-Helene
MH
Marquette
Charles-Hugo
CH
Rouby
Jean-Jacques
JJ
D000280:Administration, Inhalation; D000583:Amikacin / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D001682:Biological Availability; D007262:Infusions, Intravenous; D008168:Lung / Q000378:metabolism*; D023421:Models, Animal; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D012016:Reference Values; D012121:Respiration, Artificial; D013552:Swine; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000583:Amikacin