Individualization of tobramycin dosage in patients with cystic fibrosis

Tobramycin was administered to 52 patients, ages 2 months to 27 years, with cystic fibrosis during acute exacerbation of Pseudomonas-related pulmonary infection. Elimination pharmacokinetics of tobramycin was characterized for each patient after intravenous administration using a standardized infusion technique. The minimal inhibitory concentration was determined for Pseudomonas strains isolated from 26 of the 52 patients. The pharmacokinetic parameters of individual patient were used to adjust the dose and dosing interval to maintain the serum concentration of tobramycin above the minimal inhibitory concentration for the infecting organism for at least 75% of the dosing interval without exceeding the maximum concentration of 12 micrograms/ml or a minimum concentration of 2.0 micrograms/ml. This resulted in an increase of the mean daily dose of tobramycin to 12 mg/kg from an initial mean dose of 5.5 mg/kg and a reduction of the dosing interval from 8 hours to 4 or 6 hours for patients greater than 1 year of age. Significant differences between the pharmacokinetic profiles of the infants and older patients were observed.