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Abstract
Background: Recurrent exacerbations are the principal determinants of disease progression, hospitalization, healthcare utilization, and mortality in non-cystic fibrosis (CF) bronchiectasis. Although long-term inhaled antibiotics reduce exacerbations, the high cost of currently available agents limits their use in resource-limited settings. The reducing exacerbations with long-term inhaled amikacin for effective flare prevention (RELIEF) study evaluated the effectiveness and safety of long-term culture-guided nebulized amikacin in preventing recurrent bronchiectasis exacerbations.
Method: This prospective, comparative, two-center observational study included 144 adults hospitalized with acute exacerbation of high-resolution computed tomography (HRCT)-confirmed non-CF bronchiectasis, ≥ 3 exacerbations during the previous year, modified Reiff score > 10, and sputum cultures demonstrating resistant bacterial infection, predominantly multidrug-resistant Gram-negative organisms. Treatment allocation was determined by the treating physician; 72 patients received standard care plus culture-guided nebulized amikacin and 72 received standard care alone, with all participants followed for 52 weeks. Clinical outcomes included hospitalization duration, exacerbation frequency and severity, exacerbation duration, time to first exacerbation, exacerbation-free days, microbiological profile, antimicrobial resistance, and treatment-related adverse events.
Results: Nebulized amikacin significantly reduced hospitalization duration compared with standard care (7.48 ± 1.02 vs 12.50 ± 1.09 days; p < 0.0001). Severe exacerbations were markedly lower in the amikacin group (8 vs 26 episodes; p < 0.00012). Exacerbation duration decreased by 29.6%, 38.7%, and 40.1% for mild, moderate, and severe episodes, respectively (all p < 0.0001). Mean time to first exacerbation increased by 29.13%, 24.16%, and 17.78%, while exacerbation-free days improved by 17.71%, 27.33%, and 46.22%, respectively. Pseudomonas aeruginosa was the predominant pathogen (45.13%), with antimicrobial resistance in 64.61% of isolates. No nephrotoxicity or other significant systemic adverse events were observed throughout follow-up.
Conclusions: Long-term culture-guided nebulized amikacin was associated with reduced hospitalization duration, exacerbation burden, and recovery time while prolonging time to first exacerbation in this high-risk population. These findings support further evaluation of culture-guided nebulized amikacin as an adjunctive preventive strategy for carefully selected patients with recurrent non-CF bronchiectasis and resistant bacterial airway infection, particularly in resource-limited healthcare settings. Formal pharmacoeconomic evaluation is required before conclusions regarding cost-effectiveness can be made.
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Article Type: Original Article
ELECTRON J GEN MED, Volume 23, Issue 6, December 2026, Article No: em766
https://doi.org/10.29333/ejgm/19896
Publication date: 08 Nov 2026
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