Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease [PublishAheadOfPrint]

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 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%). Macrolide resistance and baseline AMK resistance were identified in 63 (82%) patients and five (6%) patients, respectively. Twelve months after AMK inhalation therapy, 49% of patients had symptomatic improvement, whereas 42% had radiologic improvement. Sputum negative culture conversion occurred in 14 (18%) patients, and the culture conversion rate was higher in patients infected with macrolide-susceptible isolates (7/14, 50%) than 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, sputum culture conversion was associated with mixed infections (P = 0.009), a forced expiratory volume in one second of greater than 60% (P = 0.008), and with the absence of macrolide resistance (P = 0.003). Thirty-eight percent of patients experienced adverse effects, with ototoxicity (n = 15) most common. AMK inhalation salvage therapy may improve treatment responses in some patients with refractory NTM-LD. However, considering the common adverse effects, further evaluation of optimal dosage and intervals for AMK inhalation is needed.

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