Study objective: To evaluate the efficacy and safety of tobramycin solution for inhalation (TSI) in patients with severe bronchiectasis.
Design: Open-label clinical trial consisting of three treatment cycles (14 days of drug therapy, and 14 days off drug) and an additional 40-week follow-up by chart review.
Setting: Nine clinical sites throughout the United States.
Subjects: Forty-one adult patients (≥ 18 years old) with diffuse bronchiectasis affecting two or more lung segments and a history of Pseudomonas aeruginosa infection.
Interventions: TSI, 300 mg tobramycin per dose bid.
Measurements and results: During the 12-week treatment period, significant improvements (reduction of 1.5 U [p = 0.006]) occurred in mean pulmonary total symptom severity score, a composite score that assesses the severity of cough, shortness of breath, sputum production, fatigue, and wheezing. Significant improvements (reduction of 9.8 U [p < 0.001]) were also observed in St. George Respiratory Questionnaire scores, which measure health-related quality of life. Eradication or presumed eradication of P aeruginosa occurred in 6 of 27 evaluable subjects (22.2%). Tobramycin-resistant P aeruginosa developed in two subjects (minimal inhibitory concentration ≥ 16 μg/mL). Ten subjects withdrew from the study due to adverse events; in nine of these subjects, adverse events were considered probably or possibly related to treatment. The most common adverse events were cough, wheezing, and dyspnea.
Conclusions: TSI therapy resulted in significant improvements in respiratory symptoms and health-related quality of life in subjects with severe bronchiectasis, but some subjects did not tolerate TSI therapy. Bronchiectasis patients receiving this therapy should be monitored for signs of intolerance.