805. Amikacin Liposome Inhalation Suspension (ALIS) Add-on Therapy for Refractory Mycobacterium avium Complex (MAC) Lung Disease: Effect of In Vitro Amikacin Susceptibility on Sputum Culture Conversion

BACKGROUND: ALIS (590 mg amikacin base) is liposome-encapsulated amikacin for inhalation, which delivers amikacin directly to the lung and limits systemic exposure. In the CONVERT phase 3 trial, significantly more adults with treatment-refractory MAC lung disease receiving ALIS plus guideline-based therapy (GBT) vs. GBT alone achieved sputum culture conversion by month 6 (29.0% vs. 8.9%, P < 0.0001). Amikacin treatment failure has previously been reported in patients with amikacin minimum inhibitory concentrations (MIC) >64 µg/mL. We analyzed the impact of amikacin MIC on culture conversion during treatment with add-on ALIS. METHODS: In CONVERT, patients were randomly assigned (2:1) to receive once daily ALIS+GBT (n = 224) or GBT alone (n = 112). Patients with amikacin-resistant MAC isolates (MICs >64 μg/mL by broth microdilution) were excluded prior to randomization. The primary endpoint was culture conversion, defined as 3 consecutive monthly MAC-negative sputum cultures by month 6. Amikacin MICs were correlated with culture conversion rates. RESULTS: Amikacin MIC distributions at baseline (day 1) were similar in both groups (Figure 1). Conversion rates in the ALIS+GBT arm were 28.6–34.5% for MAC with amikacin MICs of 8–64 µg/mL (Figure 2). Overall, 28 patients developed post-screening amikacin MIC >64 µg/mL, 4/112 in the GBT alone arm (post-baseline), and 24/224 in the ALIS+GBT arm (1 at baseline and 23 post-baseline after adding ALIS). Most of these (18/24) had MAC isolates with persistent amikacin MIC >64 µg/mL. Only 1/24 patients in the ALIS+GBT arm with amikacin MIC >64 µg/mL achieved culture conversion. No patient with both macrolide resistance and persistent amikacin MIC >64 µg/mL (8/24) converted. CONCLUSION: In the ALIS+GBT arm of CONVERT, culture conversion rates were similar for amikacin MICs ranging from 8–64 µg/mL at baseline. Amikacin MIC >64 µg/mL emerged in 10.3% of patients after initiation of add-on ALIS treatment, and 3.6% in the GBT alone arm. Emergent amikacin MIC >64 µg/mL was associated with failure to convert, particularly with concurrent macrolide resistance. Determining amikacin susceptibility at both treatment initiation and during treatment may have utility for guiding treatment decisions. [Image: see text] [Image: see text] DISCLOSURES: B. A. Brown-Elliott, Insmed: Investigator, Research support. G. Eagle, Insmed Incorporated: Employee, Salary. R. J. Wallace, Insmed: Investigator, Research support. J. Van Ingen, Insmed: Investigator, Research support. L. J. Pennings, Insmed: Investigator, Research support. B. Berry, Insmed: Investigator, Research support. S. Pandey, Insmed: Investigator, Research support. C. Coulter, Insmed: Investigator, Research support. M. Syrmis, Insmed: Investigator, Research support. K. L. Winthrop, Insmed Incorporated: Consultant and Scientific Advisor, Consulting fee and Research grant. D. E. Griffith, Aradigm Corporation: Advisor/consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Bayer Healthcare Pharmaceuticals: Advisor/consultant, Consulting fee. Grifols: Advisor/consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Insmed Incorporated: Advisor/consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Grant recipient and Speaker honorarium.