Inhaled Antibiotic Added at Diagnosis Helps More People Clear MAC Lung Infections

For people with Mycobacterium avium complex (MAC) lung disease, treatment usually means at least a year of daily antibiotics, and many still don’t clear the infection. New data from a large phase 3b trial suggest that adding an inhaled antibiotic to standard treatment for people who are newly diagnosed may help more of them clear the infection.

The findings come from the ENCORE trial. The primary results were presented at the American Thoracic Society International Conference in May 2026, and a new analysis on drug resistance was presented at IDWeek 2026 in October.

A chronic infection with limited treatment options

MAC lung disease is the most common type of nontuberculous mycobacterial lung disease. It is a chronic infection that can cause a lasting cough, fatigue, shortness of breath and weight loss. According to the ATS abstract, it is linked to declining lung function, poor quality of life and a five-year all-cause death rate as high as 42%.

Standard treatment combines several oral antibiotics, typically a macrolide such as azithromycin along with ethambutol. Arikayce (amikacin liposome inhalation suspension) is an inhaled antibiotic that delivers amikacin directly to the lungs. It currently has accelerated FDA approval only for refractory MAC lung disease, meaning infections that haven’t cleared after at least six months of standard therapy.

Charles L. Daley, M.D., of National Jewish Health, who presented the primary results, explained the reason for testing it earlier. “Why are we waiting for people to fail to give it to them?” he said in an interview with HCPLive.

Higher clearance rates at every checkpoint

ENCORE enrolled 425 adults at 177 sites worldwide, according to Insmed, which makes Arikayce. All participants had noncavitary MAC lung disease, had respiratory symptoms and had not yet taken antibiotics for their current infection. Everyone received azithromycin and ethambutol for 12 months. Half also received Arikayce, and the other half received an inactive inhaled placebo.

The main goal of treatment is culture conversion, which means a person’s sputum samples no longer grow the bacteria. By month 12, 84.7% of people in the Arikayce group had culture conversion, compared with 61.3% in the placebo group. Three months after treatment ended, 76.2% of the Arikayce group still had negative cultures, compared with 47.6% of the placebo group.

The trial’s primary endpoint was a patient-reported respiratory symptom score. Symptoms improved in both groups, and the improvement was modestly but significantly greater with Arikayce.

Drug resistance stayed rare

Antibiotic resistance is a major concern in MAC lung disease because amikacin and macrolides are the backbone of treatment. The IDWeek analysis looked at people who had at least one positive culture during the study. Among them, 2 of 93 people in the Arikayce group (2.2%) developed amikacin-resistant bacteria. Macrolide resistance appeared in 1 of 93 people in the Arikayce group (1.1%) and 3 of 165 in the placebo group (1.8%). The researchers did not statistically compare resistance rates between the groups.

Kevin L. Winthrop, M.D., M.P.H., professor of medicine in the division of infectious diseases at Oregon Health & Science University, presented the resistance findings. “We want to preserve amikacin. We want to preserve macrolide susceptibility,” he told Contagion Live.

The FDA has granted Priority Review to Insmed’s application for full approval of Arikayce in people with newly diagnosed or recurrent MAC lung disease. A decision is expected by Jan. 28, 2027.