Tobramycin penetration into epithelial lining fluid of patients with pneumonia

Objective: To study the penetration of tobramycin in lung tissue evaluated as the concentration in epithelial lining fluid and to characterize the tim e course of the drug in the treatment of patients with pneumonia, Methods: The subjects were 16 patients with pneumonia and taking tobramycin who had clinical indications for bronchoscopy, Bronchoscopy with bronchoal veolar lavage of the pneumonic area was performed once on each patient 1/2, 2, 4, or 8 hours after the previous tobramycin dose, Urea was used as an e ndogenous marker for quantification of epithelial lining fluid obtained at bronchoalveolar lavage. Tobramycin concentrations in serum were measured fo r all patients at the aforementioned 4 time points. Tobramycin concentratio n was determined by means of fluorescent polarization immunoassay modified for bronchoalveolar samples, Results: Levels of tobramycin in the fluid of the epithelial lining were 2. 33 +/- 0.5 at 1/2 hour, 1.67 +/- 0.6 at 2 hours, 1.62 +/- 1.19 at 4 hours, and 0.77 +/- 0.38 mu g/mL at 8 hours. The ratio of epithelial lining fluid to serum concentration of tobramycin was 0.30 +/- 0.03 at 1/2 hour, 0.42 +/ - 0.16 at 2 hours, 0.64 +/- 0.37 at 4 hours, and 1.53 +/- 0.76 at 8 hours. The ratio at peak serum time was similar to that reported for tobramycin an d netilmicin. Conclusions High peak serum concentrations of tobramycin are necessary to o btain microbiologically active concentrations at the alveolar level. The fl uid of the epithelial lining constitutes a deep compartment for aminoglycos ides, The disappearance of tobramycin was slower than at the serum level.