Randomised controlled trial of nebulised gentamicin in children with bronchiectasis.

Abstract

Following trials of inhaled antibiotics in adults, this study investigates the efficacy of nebulised gentamicin to improve respiratory function in children with bronchiectasis. This is a randomised, double-blind, placebo-controlled, crossover trial of 12-week nebulised placebo/gentamicin, 6-week washout, 12-week gentamicin/placebo. Participants were children (5-15 years) with bronchiectasis, chronic infection (any pathogen), and able to perform spirometry from a hospital bronchiectasis clinic. Primary outcomes were change in forced expiratory volume in 1 s (FEV1 ) and hospitalisation days. Secondary outcomes included sputum bacterial density, sputum inflammatory markers, additional antibiotics and symptom severity. Analyses were on an intention-to-treat basis. Fifteen children (mean 11.7-years-old) completed the study. There was no significant change in mean FEV1 (56%/55%, P = 0.38) or annual rate of hospital admissions (1.1/0, P = 0.12) between gentamicin and placebo, respectively. However, Haemophilus influenzae sputum growth (27% vs. 80%, P = 0.002) and bacterial density (2.4 log10 cfu/mL lower P < 0.001) improved with gentamicin. Sputum inflammatory markers interleukin-1β (P < 0.001), interleukin-8 (P < 0.001) and tumour necrosis factor-α (P = 0.003) were lower with gentamicin. Poor recruitment limited study power and treatment adherence was challenging for this cohort. In this crossover study of nebulised gentamicin in children with bronchiectasis, there was a reduction in sputum bacterial density and inflammation. However, there were no major improvements in clinical outcomes and adherence was a challenge.