A pilot study of the safety and efficacy of tobramycin solution for inhalation in patients with severe bronchiectasis.

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 microg/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.