Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease

Antimicrob Agents Chemother. 2018 Jun 26;62(7):e00011-18. doi: 10.1128/AAC.00011-18. Print 2018 Jul.

Abstract

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.

Keywords: Mycobacterium abscessus; Mycobacterium avium complex; amikacin; inhalation; nontuberculous mycobacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aged
  • Amikacin / administration & dosage
  • Amikacin / adverse effects*
  • Amikacin / therapeutic use*
  • Anti-Bacterial Agents / therapeutic use*
  • Drug Resistance, Bacterial
  • Drug Therapy, Combination
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium Infections, Nontuberculous / drug therapy*
  • Mycobacterium Infections, Nontuberculous / microbiology
  • Mycobacterium abscessus / drug effects*
  • Mycobacterium abscessus / isolation & purification
  • Mycobacterium avium Complex / drug effects*
  • Mycobacterium avium Complex / isolation & purification
  • Retrospective Studies
  • Salvage Therapy / methods*
  • Sputum / microbiology
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Amikacin