Early-phase efficacy and adverse effects of liposomal amikacin inhalation for refractory Mycobacterium avium complex lung disease: A case series

Abstract Background Amikacin liposome inhalation suspension (ALIS), which efficiently allows amikacin to reach the pulmonary periphery for drug effect while minimising systemic adverse effects, was recently approved for the treatment of Mycobacterium avium complex (MAC) infections. The international phase 3 open-label clinical trials showed promising results, contributing to sputum culture conversion, but few reports have examined the efficacy and adverse effects using real-world data. We have identified the clinical outcome and adverse effects in the early-phase of treatment to use ALIS more effectively and safely in clinical practice. Methods The study population consisted of patients with MAC lung disease (MAC-LD) who were introduced to ALIS therapy after July 2021 at Keio University Hospital due to poor response to multidrug therapy. The sputum smear/culture results, symptoms and adverse effects of the early-phase of ALIS inhalation therapy were retrospectively reviewed. The serum amikacin concentrations in the earliest phase were also measured to assess PK/PD. Results A total of 11 cases (9 women; median age 64.6 years) were included in this study. The median disease duration of MAC-LD was 13.7 years, and all patients had a positive culture at the beginning of ALIS inhalation. Eight patients (72.7%) completed ALIS inhalation without interruption during the first month of treatment. Five patients (45.5%) were smear-negative at the start and none were positive at the 1 month follow-up. Three of the six patients (50.0%) who were sputum-smear-positive at the initiation were confirmed to have become sputum-smear-negative within one month, including one culture conversion. ALIS inhalation therapy caused some adverse effects in nine patients (81.8%); however, no serious systemic adverse effects were observed. The most common adverse effect was hoarseness (72.7%), which mostly occurred around 1 week after initiation. The medians of peak serum amikacin concentrations were 1.4 and 2.3 µg/mL for the first and third inhalations, respectively. On the other hand, trough serum concentrations just before the third inhalation were < 1.2 µg/mL in all patients. Conclusions ALIS therapy might be a treatment option for patients having refractory MAC infection with long disease duration who have had a poor response to guideline-based therapy.