Abstract Rationale Refractory pulmonary Mycobacterium avium complex (MAC) disease often remains culture-positive despite guideline-based therapy, and prolonged ineffective treatment may lead to the development of macrolide resistance, which is associated with poor outcomes. The effectiveness of amikacin liposome inhalation suspension (ALIS) may therefore depend on the timing and clinical context in which it is introduced. Methods We conducted a multicenter retrospective cohort study of adults with refractory pulmonary MAC disease treated with ALIS across four affiliated hospitals. The primary outcome was 6-month sputum culture conversion. Associations with baseline acid-fast bacillus (AFB) smear status, prior aminoglycoside exposure, macrolide susceptibility, and radiographic pattern (nodular/bronchiectatic vs cavitary) were assessed. Safety outcomes were collected from clinical documentation. Results Forty-six patients were included (median age 73 years). Among 29 evaluable patients, 13 achieved culture conversion at 6 months (45%). Conversion was more frequent when ALIS was initiated in patients who were smear-negative compared with smear-positive (85.7% vs 31.8%, p = 0.012), and in aminoglycoside-naïve compared with previously exposed patients (63.2% vs 20.0%, p = 0.027). A consistent trend suggested improved outcomes when ALIS was introduced in macrolide-susceptible disease compared with macrolide-resistant/intermediate disease (55.6% vs 27.2%, p = 0.13), and similarly in nodular-bronchiectatic compared with cavitary disease (63.2% vs 25.0%, p = 0.11). Adverse events were mainly mild localized airway symptoms such as hoarseness, and overall tolerability was favorable. Conclusion The effectiveness of ALIS in refractory pulmonary MAC disease was influenced by the clinical context at the time of initiation. Microbiologic response was more likely when ALIS was introduced before AFB smear positivity and before prior aminoglycoside exposure, and a trend toward improved outcomes was observed when introduced prior to the development of macrolide resistance, although culture conversion remained achievable in some resistant cases. These findings support proactive, early initiation of ALIS, highlighting treatment timing as a modifiable determinant of clinical success. This abstract is funded by: None
Tone et al. (Fri,) studied this question.