OBJECTIVE: To study the safety and tolerability of nebulized amoxicillin + clavulanic acid in patients with stable COPD. Acute exacerbations in COPD are often treated with antibiotics. Previous studies showed ineffective amoxicillin concentrations in sputum in two thirds of the patients treated with systemic amoxicillin + clavulanic acid. Local administration, theoretically providing higher concentrations, has not been described before. DESIGN: Prospective observational intervention study. METHODS: Nine subjects received ascending doses amoxicillin + clavulanic acid, ranging from 50 + 10 mg up to 300 + 60 mg. Plasma and expectorated sputum samples were assayed for amoxicillin content. Safety was evaluated by spirometry before and after nebulization. Tolerability was evaluated by questionnaire. RESULTS: Spirometry showed no clinically relevant reduction in FEV1 after nebulization with amoxicillin + clavulanic acid. In 34 nebulizations only 3 mild adverse events occurred. The sputum amoxicillin quantification showed levels well above MIC90, while no effective levels were found in plasma. CONCLUSION: Inhalation of nebulized amoxicillin + clavulanic acid is safe and well tolerated. Nebulized amoxicillin + clavulanic acid produces sputum concentrations well above MIC with low systemic exposure.
|Number of pages||5|
|Publication status||Published - 23 Jan 2015|