Real-world Experience With Inhaled Liposomal Amikacin Suspension for Treatment of Nontuberculous Mycobacterial Pulmonary Disease

Abstract Rationale. Guideline based therapy (GBT) for Mycobacterium avium complex (MAC) infections consists of a three-drug regimen (macrolide + ethambutol + rifamycin).1 Patients who fail to culture convert their sputum to negative after six-months of (GBT) are deemed refractory. Guidelines recommend the addition of amikacin liposomal inhalation suspension (ALIS). ALIS was FDA approved in 2018 for this indication but is currently only available in Australia under a compassionate use programme. Methods. Identification of refractory patients treated with ALIS was undertaken at three speciality mycobacterial clinics in Brisbane, Australia. Baseline demographics, duration of GBT and ALIS therapy were recorded. Patients were asked to submit monthly sputum cultures. Successful therapy was defined as the achievement of 12-months of negative sputum cultures whilst on therapy. Results. From 2015 – 2024, 43 patients receiving ALIS were identified. Mean age at commencement of ALIS was 63 years (SD ±10); 77% were female. The most common NTM infection was M. i ntracellulare (58%), followed by M. a vium (21%) and M. a bscessus (9%). Radiology revealed nodular bronchiectasis (NB) in 38, NB with cavities and fibrocavitary changes in three patients each. The most common background regimens were macrolide and ethambutol based with; clofazimine (37%) or a rifamycin (30%). Twelve patients (28%) were on a four-drug oral regimen at the time of commencing ALIS. Two patients (5%) were on an alternate three-drug combination due to tolerability issues. Mean duration of GBT prior to ALIS was 2.8 years (SD± 2.3 yr). No serious TEAE were reported. The most prevalent TEAE were dysphonia (56%) and cough (47%). Temporary interruption was required in 20 patients (47%) however an intermittent dosing regimen (e.g., second daily administration) led to better tolerability and sustained compliance in all but three (7%) patients, who ceased therapy. Haemoptysis was infrequently reported and self-limiting (14%). Bilateral upper lobe ground glass infiltrates on CT imaging were noted in five (12%) patients during treatment with ALIS. ALIS was continued and radiological changes resolved on post-treatment imaging. Sputum culture conversion was achieved in 21 patients (62%) within six months of commencement of ALIS, increasing to 26 patients (76%) at 12 months with continued treatment. Culture conversion in M. abscessus patients at six months was 80% (n = 4). Conclusions. Our real-world experience of ALIS shows that it is a well-tolerated and efficacious add-on therapy in patients with NTM-PD. TEAE reported in our study were non-serious and did not result in substantial treatment discontinuation.