Study objective: To determine whether adequate concentrations of a new formulation of tobramycin could be delivered to the lower respiratory tract of patients with cystic fibrosis (CF) using a jet nebulizer delivery system.
Design: A multicenter, open-label, randomized, crossover study.
Setting: Ten tertiary care, university-affiliated, teaching hospitals in the United States.
Patients and control subjects: Sixty-eight patients recruited from 10 CF Foundation centers and who were at least 8 years of age, had a diagnosis of CF, and expectorated daily sputum. No control subjects enrolled.
Interventions: Each patient received one administration of aerosolized tobramycin from each of the three nebulizer systems in random order. Each administration was separated by a minimum of 48 h. The two jet nebulizer systems tested were the Sidestream (Medic-Aid; Sussex, UK), and the Pari LC (Pari Respiratory Equipment; Richmond, Va), with a DeVilbiss Pulmoaide compressor (DeVilbiss Health Care; Somerset, Pa), both administering 300 mg tobramycin in 5 mL of ¼ normal saline solution (NS). Patients were also administered 600 mg tobramycin in 30 mL of ½ NS with the UltraNeb 99/100 (DeVilbiss).
Measurements: Sputum and serum tobramycin concentration and pulmonary function were monitored. An adequate peak sputum tobramycin concentration was defined as >128 µg/g sputum at any of three time points (10, 60, or 120 min) after completion of treatments.
Results: The peak tobramycin concentrations in expectorated sputum were 687±663 µg/g (mean±SD) with the Pari LC and 489±402 µg/g with the Sidestream. Adequate peak sputum tobramycin concentration was achieved in 93% of the patients with the Sidestream, and in 87% of the patients with the Pari LC. Peak sputum concentrations were found to be substantially higher when patients received tobramycin administered with the UltraNeb 99/100, 1,498±1,331 µg/g with 30% of patients having levels exceeding 2,000 µg/g. Serum tobramycin concentrations were ≤4 µg/mL for all patients following administration with each nebulizer.
Conclusions: Adequately high sputum tobramycin concentrations were documented in sputum in >85% of patients following the administration of 300 mg/5 mL formulation of tobramycin aerosolized by the two jet nebulizer delivery systems, Sidestream and Pari LC. The single tobramycin administration delivered by these two systems is well-tolerated.