Open-Label Trial of Amikacin Liposome Inhalation Suspension in Mycobacterium abscessus Lung Disease

Abstract

Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows invitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance. Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in treatment-refractory and treatment-naïve patients with M abscessus pulmonary disease? In an open-label protocol, patients were given ALIS (590mg) added to background multidrug therapy for 12months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance. Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were women, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine, or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%). In a cohort of patients primarily with macrolide-resistant M abscessus, half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy. ClinicalTrials.gov; No.: NCT03038178; URL: www. gov.