Amikacine liposomale par inhalation orale pour le traitement des infections pulmonaires à Mycobacterium avium complex

Liposomal inhaled antibiotic for M. avium lung complex disease/ Amikacine liposomale par inhalation orale pour le traitement des infections pulmonaires à Mycobacterium avium complex

Nontuberculous mycobacteria (NTM) consist of a large group of mycobacterial species/ subspecies (close 200) not belonging to M. tuberculosis complex, M. leprae and M. ulcerans and can be found in a wide variety of both natural and artificial environments. NTM are opportunistic pathogens with varying virulence among NTM species and the most common site of infection is the lung. NTM are intrinsically resistant to most antibiotics and evade host defense through formation of biofilms and sequestration into host cells, in particular macrophages. Treatment of NTM lung disease is lengthy and requires complex multidrug regimens with suboptimal patient outcomes. Amikacin is an aminoglycoside with anti-NTM activity in, but systemic delivery is associated with limited lung penetration in the lungs, poor cellular uptake and a high risk of systemic safety issues. Liposomes are spherical lipid vesicles used for drug delivery to control drug release, affect pharmacokinetics and reduce drug toxicity. ALIS is a nebulized liposome encapsulated formulation of amikacin developed for targeting NTM lung infection by Mycobacterium avium complex (MAC). Inhalation results in local targeting of the NTM infection in the lungs, enhancing amikacin concentration at the site of infection and limiting systemic exposure. The neutrally charged liposome loaded with amikacin ensures biofilm penetration and alveolar macrophage uptake superior to non-liposomal amikacin. ALIS added to multi-drug therapy has demonstrated success in the treatment of refractory MAC lung disease and is authorized in Europe, USA and Japan.

Reference: Chalmers JD, van Ingen J, van der Laan R, Herrmann JL. Liposomal drug delivery to manage nontuberculous mycobacterial pulmonary disease and other chronic lung infections.
Eur Respir Rev 2021; 30: 210010 [DOI: 10.1183/16000617.0010-2021]

Link to the article: https://err.ersjournals.com/content/30/161/210010

Contact: jean-louis.herrmann@aphp.fr