Safety and Tolerability of Nebulized Amoxicillin-Clavulanic Acid in Patients with COPD (STONAC 1 and STONAC 2)

Abstract

The safety and tolerability of nebulized amoxicillin clavulanic acid were determined in patients with stable COPD and during severe exacerbations of COPD. Nine stable COPD patients received doses ranging from 50:10 mg up to 300:60 mg amoxicillin clavulanic acid and eight patients hospitalised for a COPD exacerbation received fixed doses 200/40 mg twice daily. Safety was evaluated by spirometry before and after inhalation. Tolerability was evaluated by questionnaire. Plasma and expectorated sputum samples were assayed for amoxicillin content. Seventeen patients underwent in total 100 nebulizations with amoxicillin clavulanic acid. In this safety and tolerability study no clinically relevant deteriorations in FEV1 were observed. Nebulized amoxicillin clavulanic acid produces sputum concentrations well above the Minimal Inhibiting Concentration of 90% for potential pathogenic micro-organisms, with low concentrations in the central compartment (low systemic exposure). Based on spirometry and reported side effects, inhalation of nebulized amoxicillin clavulanic acid seems to be safe and well tolerated, both in stable patients with COPD as in those experiencing a severe exacerbation. Levels of amoxicillin were adequate.

Antibacterial therapy: questions posed by COVID-19 and real clinical practice

“…В 2013 г. немецкие исследователи отмечали высокую эффективность АКК при бактериальных обострениях хронической обструктивной болезни легких (ХОБЛ), проявлявшуюся существенным увеличением времени до следующего обострения [17]. Исследователи из Нидерландов показали эффективность и безопасность ингаляционной формы АКК у пациентов с бактериальными обострениями ХОБЛ [18]. Отечественные авторы, опубликовавшие аналитический обзор по применению АКК при инфекциях нижних дыхательных путей, отмечали также, что высокий профиль безопасности, возможность применения у беременных женщин являются его неоспоримыми преимуществами, и в ближайшей перспективе защищенные пенициллины, вероятнее всего, останутся препаратами первой линии у большинства пациентов с респираторной инфекцией [19].…”

Current Challenges in Chronic Bronchial Infection in Patients with Chronic Obstructive Pulmonary Disease

“…However, clinical trials demonstrating its efficacy in COPD patients are lacking. Only some studies have evaluated the efficacy of inhaled colistin, tobramycin, or amoxicillin-clavulanic acid in patients with COPD (Table 5) [100][101][102][103]. These were either single-center uncontrolled trials or retrospective studies.…”