Inhaled Amikacin Shows Low Resistance Rates in MAC Lung Disease in ENCORE

According to the study authors of the phase 3b ENCORE trial, adding amikacin liposome inhalation suspension (ALIS; Arikayce; Insmed) to multidrug therapy (MDT) produced significantly higher culture conversion rates in patients with newly diagnosed Mycobacterium avium complex lung disease (MACLD).¹ Treatment-emergent amikacin and macrolide resistance remained uncommon in both study arms. The findings were presented at IDWeek 2026, held October 21-24 in Washington, DC.¹

Antibiotic resistance in MACLD is associated with low culture conversion rates, limited treatment options, and increased mortality.¹ ENCORE evaluated ALIS earlier in the disease course, enrolling patients with initial or subsequent MACLD who had not yet started antibiotics for their current infection.

“We have for a long time wanted to try ALIS from the get-go in treatment initiators,” said Kevin Winthrop, MD, professor of medicine, division of infectious diseases, School of Medicine, Oregon Health & Science University in Portland. “The people on the three-drug arm did quite well. They did better than the two-drug arm with regards to all the outcomes measured.”

ENCORE (NCT04677569) was a randomized, double-blind, multinational, placebo-controlled superiority trial.¹,² Investigators randomly assigned 425 patients 1:1 to once-daily azithromycin 250 mg and ethambutol 15 mg/kg plus either ALIS 590 mg (n = 213) or an empty liposome control (n = 212) for 12 months. Patients with a resistant MAC isolate at screening were excluded.¹

Of 761 patients screened, five were ineligible because of baseline resistance, including two with amikacin resistance and three with clarithromycin resistance.¹ All MAC-positive sputum cultures underwent drug susceptibility testing, with resistance defined as an amikacin MIC of at least 128 µg/mL and/or a clarithromycin MIC of at least 32 µg/mL. Culture conversion was significantly higher in the ALIS arm than in the comparator arm.

Amikacin and Macrolide Resistance Rates During and After ALIS Treatment

Drug resistance emerged rarely during ENCORE.¹ In the ALIS arm, two patients (2.2%) developed MAC isolates with amikacin resistance. Clarithromycin resistance occurred in four patients overall, including one (1.1%) in the ALIS arm and three (1.8%) in the comparator arm.

Adherence and sampling were high across the trial. Study completion exceeded 90%, treatment completion exceeded 80%, and treatment compliance exceeded 90%.¹ More than 95% of patients had sputum samples collected at completed study visits.

The investigators concluded the combination of higher culture conversion and low treatment-emergent resistance supports ALIS with MDT as an effective MACLD treatment option.¹ Low resistance emergence is clinically relevant because amikacin and macrolides anchor current MAC regimens. Loss of susceptibility to either class leaves clinicians with few remaining options.

Winthrop makes the point that amikacin is the workhorse therapy and it is important to use it judicially. “We want to preserve amikacin. We want to preserve macrolide susceptibility…. we can maintain the utility or usefulness of those two drugs, the patient has a much better chance of success,” Winthrop said.

ALIS currently holds US accelerated approval for adults with refractory MACLD who have limited or no alternative treatment options.³ ENCORE extends the evidence base to patients starting treatment for the first time or for a new infection episode.

REFERENCES:

1. Winthrop K. et al. Amikacin and Macrolide Resistance in Patients With Newly Diagnosed Mycobacterium avium Complex Lung Disease: Results From ENCORE. Presented at: IDWeek 2026; October 2026. Washington DC.

2. ENCORE: amikacin liposome inhalation suspension with background regimen in newly diagnosed MAC lung disease. ClinicalTrials.gov identifier: NCT04677569. Accessed October 22, 2026. https://clinicaltrials.gov/study/NCT04677569

3. Arikayce. Prescribing information. Insmed Incorporated; 2018.