Journal Article

A Randomized Controlled Trial of Nebulized Gentamicin in Non–Cystic Fibrosis Bronchiectasis

Chalmers, James D., Simpson, A. John, Govan, John R. W., Doherty, Catherine J., Greening, Andrew P., Murray, Maeve P., Haslett, Christopher, Wilkinson, Thomas S., Hill, Adam T.

2011

Overview

Abstract Rationale Bronchiectasis is a chronic debilitating disease with few evidence-based long-term treatments. Objectives A randomized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non–cystic fibrosis bronchiectasis. Methods Sixty-five patients were randomized to either twice-daily nebulized gentamicin, 80 mg, or nebulized 0.9% saline, for 12 months. All were reviewed at three-monthly intervals during treatment and at 3 months' follow-up. Measurements and Main Results At each review the following were assessed: quantitative and qualitative sputum bacteriology; sputum purulence and 24-hour volume; FEV1, FVC, and forced expiratory flow, midexpiratory phase; exercise capacity; Leicester Cough Questionnaire and St. George's Respiratory Questionnaire; and exacerbation frequency. Fifty-seven patients completed the study. At the end of 12 months' treatment, compared with the saline group, in the gentamicin group there was reduced sputum bacterial density with 30.8% eradication in those infected with Pseudomonas aeruginosa and 92.8% eradication in those infected with other pathogens; less sputum purulence (8.7% vs. 38.5%; P < 0.0001); greater exercise capacity (510 [350–690] m vs. 415 [267.5–530] m; P = 0.03); and fewer exacerbations (0 [0–1] vs. 1.5 [1–2]; P < 0.0001) with increased time to first exacerbation (120 [87–161.5] d vs. 61.5 [20.7–122.7] d; P = 0.02). The gentamicin group had greater improvements in Leicester Cough Questionnaire (81.4% vs. 20%; P < 0.01) and St. George's Respiratory Questionnaire (87.5% vs. 19.2%; P < 0.004) score. No differences were seen in 24-hour sputum volume, FEV1, FVC, or forced expiratory flow, midexpiratory phase. No P. aeruginosa isolates developed resistance to gentamicin. At follow-up, all outcome measures were similar to baseline. Conclusions Regular, long-term nebulized gentamicin is of significant benefit in non–cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy. Clinical trial registered with www.clinicaltrials.gov (NCT00749866).

• Publisher: Oxford University Press,American Thoracic Society
• Subject: Administration, Inhalation / Aerosols / Aged / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Anti-Bacterial Agents - administration & dosage / Antibiotics / Bacteriology / Biological and medical sciences / Bronchiectasis - drug therapy / Clinical trial. Drug monitoring / Clinical trials / Cystic fibrosis / Female / Follow-Up Studies / General pharmacology / Gentamicins - administration & dosage / Humans / Inflammation / Intensive care medicine / Male / Medical sciences / Middle Aged / Pathogens / Pharmacology. Drug treatments / Pulmonary arteries / Quality of life / Questionnaires / Respiratory Function Tests - methods / Respiratory Function Tests - statistics & numerical data / Sodium Chloride - administration & dosage / Surveys and Questionnaires / Treatment Outcome