Report on Successful Treatment of Refractory MAC 2 Lung Disease in Two Elderly Patients with Inhaled Liposomal Amikacin (ALIS) at Half the Standard Dose.

"Nontuberculous mycobacteria" (NTM) is a general term for mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. In Japan, 90% of pulmonary NTM disease cases are caused by two species, Mycobacterium avium and M. intracellulare, which are collectively referred to as Mycobacterium avium complex (MAC) due to their biochemical similarity. Pulmonary MAC disease is broadly classified into fibrocavitary and nodular/bronchiectatic types, each of which exhibits distinctive pathological features. The pulmonary NTM disease incidence has been found to be 14.7 cases per 100,000 population per year, suggesting that Japan has the highest incidence of this disease in the world, and its incidence has also been shown to have already exceeded that of pulmonary tuberculosis. In addition, many elderly people have weakened immune systems, which often causes a decline in comprehension, and many medications for this have side effects, making it difficult to continue taking them and leading to treatment difficulties. The two cases reported here were both elderly women with refractory MAC lung disease, but they had different phenotypes: a fibrocavitary type and a long-standing, progressive nodular and bronchiectatic type. Treatment was performed with a regimen using Liposomal amikacin (ALIS), which is an aminoglycoside antibiotic that works by binding to bacterial Riposomes and inhibiting protein synthesis. Using amikacin Liposomal technology and a specialized inhaler, ALIS efficiently reaches alveolar macrophages, directly killing the MAC bacteria within. However, the unique administration method requires inhaler cleaning, making continued use difficult given the characteristics of patients with refractory MAC pulmonary disease. Even when treatment is possible, frequent side effects, such as hoarseness and dysphonia, while not severe, further contribute to the difficulty of initiating treatment. In both cases reported here, continued administration of rifampicin was difficult due to side effects such as liver damage and loss of appetite, and the patients' conditions were also resistant to treatment, so ALIS was chosen, as it is thought to be more effective than other drugs and to have fewer systemic side effects. The patient had a limited understanding of how to clean the inhaler and how to inhale, making continued treatment difficult; therefore, we explained the efficacy and safety of ALIS to the patient's family. Inhalation therapy is an effective method for delivering medication directly to the lungs, where the disease is located, while reducing systemic side effects. Until now, no inhalation therapy has existed for pulmonary MAC disease, and inhalation therapy itself is still a groundbreaking treatment administration method. This is the first case in the world where therapeutic efficacy has been confirmed with fewer than half the number of treatments required for standard treatment. Furthermore, as a new drug delivery method, inhalation offers a novel treatment option when existing medications are unavailable or ineffective for some reason, and it may be safe for use in elderly patients.