Although guidelines recommend amikacin (AMK) inhalation therapy for difficult-to-treat nontuberculous mycobacterial lung disease (NTM-LD), data are limited regarding the safety and clinical efficacy of this salvage therapy. We retrospectively evaluated the treatment outcomes of 77 patients with refractory NTM-LD caused by Mycobacterium abscessus complex (MABC) or M. avium complex (MAC) who initiated AMK inhalation therapy between February 2015 and June 2016. MABC was the most common etiology (n 48, 62%), followed by MAC (n 20, 26%) and mixed infections (n 9, 12%). Isolates with macrolide resistance and baseline AMK resistance were identified in 63 (82%) patients and 5 (6%) patients, respectively. At 12 months after AMK inhalation therapy, 49% of patients had symptomatic improvement, whereas 42% had radiological improvement. Conversion to a negative sputum culture occurred in 14 (18%) patients, and the culture conversion rate was higher in patients infected with macrolide-susceptible isolates (7/14, 50%) than in those infected with macrolide-resistant isolates (7/63, 11%) (P 0.003). Significant decreases in sputum semiquantitative culture positivity occurred after AMK inhalation therapy (P 0.001). On multivariate analysis, conversion to a negative sputum culture was associated with mixed infections (P 0.009), a forced expiratory volume in 1 s of greater than 60% (P 0.008), and the absence of macrolide resistance (P 0.003). Thirty-eight percent of patients experienced adverse effects, with ototoxicity (n 15) being the most common. AMK inhalation salvage therapy may improve the treatment responses in some patients with refractory NTM-LD. However, considering the common adverse effects, further evaluation of the optimal dosage and intervals for AMK inhalation therapy is needed.
Bibliographical noteFunding Information:
Charles L. Daley has received grants from Insmed, Inc. However, this relationship is not associated with the submitted work. Hye Yun Park has received lecture fees from AstraZeneca, Novartis, and Boehringer-Ingelheim; however, these are not associated with the submitted work. We have no other conflicts of interest to declare. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning (NRF-2015R1A2A1A01003959). Additional support was provided by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2778). The sponsors had no role in the study design, data collection and analysis, or manuscript preparation.
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All Science Journal Classification (ASJC) codes
- Pharmacology (medical)
- Infectious Diseases