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Aim: Following trials of inhaled antibiotics in adults, this study investigates the efficacy of nebulised gentamicin to improve respiratory function in children with bronchiectasis. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Abstract: Nebulised antibiotic therapy is an established, safe and effective therapy for cystic fibrosis with chronic pseudomonas infection resulting in improved pulmonary function and reduced hospitalisation. Despite similar respiratory disease, this therapy has not been evaluated in children with non cystic fibrosis bronchiectasis. This study evaluates the suitability of a gentamicin solution and nebuliser combination for use in this population. Materials and methods:: Four millilitres of gentamicin (80mg) in saline delivered by a PARI LC plus® nebuliser and PARI Turboboy N® compressor was used. The pH, osmolarity, chloride concentration and aerosol particle size was determined. Ten children with non cystic fibrosis bronchiectasis received nebulised antibiotic and had peak gentamicin concentrations measured in sputum and serum. Pulmonary function was measured pre and post nebulisation. Results:: The solution had an osmolarity of 199mOsm/l, pH of 4.1, chloride concentration of 75mmol/l and the aerosol a mass median aerodynamic diameter of 3.3μm. Nebulisation was well tolerated, with no significant change in FEV1. Peak serum levels were at the threshold of detectability (0.3mg/l). Sputum concentrations had a mean of 624mg/g and lower 95th confidence interval 25 times the minimum inhibitory concentration for the predominant infecting organism, Haemophilus influenzae. Conclusion:: Nebulisation of 80mg of gentamicin in saline achieved bactericidal concentrations in sputum, was well tolerated and had negligible systemic absorption making it a suitable choice for this population. [Copyright &y& Elsevier]