Background: Ventilator-associated pneumonia is common and is treated using nebulized antibiotics. Although adequate pulmonary biodistribution is important for antibiotic effect, there is a lack of data for both intravenous (IV) and nebulized antibiotic administration during mechanical ventilation.
Objective: To describe the comparative pulmonary regional distribution of IV and nebulized technetium-99m-labeled tobramycin (Tc-tobramycin) 400 mg in a mechanically-ventilated ovine model.
Methods: The study was performed in a mechanically-ventilated ovine model. Tc-tobramycin 400 mg was obtained using a radiolabeling process. Computed tomography (CT) was performed. Ten sheep were given Tc-tobramycin 400 mg via either an IV (five sheep) or nebulized (five sheep) route. Planar images (dorsal, ventral, left lateral and right lateral) were obtained using a gamma camera. Blood samples were obtained every 15 min for 1 h (4 time points) and lung, liver, both kidney, and urine samples were obtained post-mortem.
Results: Ten sheep were anesthetized and mechanically ventilated. Whole-lung deposition of nebulized Tc-tobramycin 400 mg was significantly lower than with IV (8.8% vs. 57.1%, P<0.001). For both administration routes, there was significantly lower deposition in upper lung zones compared with the rest of the lungs. Dorsal deposition was significantly higher with nebulized Tc-tobramycin 400 mg compared with IV (68.9% vs. 58.9%, P=0.003). Lung concentrations of Tc-tobramycin were higher with IV compared with nebulized administration. There were significantly higher concentrations of Tc-tobramycin in blood, liver and urine with IV administration compared with nebulized.
Conclusions: Nebulization resulted in lower whole and regional lung deposition of Tc-tobramycin compared with IV administration and appeared to be associated with low blood and extra-pulmonary organ concentrations.
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