Amikacin inhalation as salvage therapy for refractory nontuberculous mycobacterial lung disease

Byung Woo Jhun, Bumhee Yang, Seong Mi Moon, Hyun Lee, Hye Yun Park, Kyeongman Jeon, O. Jung Kwon, Jungmin Ahn, Il Joon Moon, Sung Jae Shin, Charles L. Daley, Won Jung Koh

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Article numbere00011-18
JournalAntimicrobial agents and chemotherapy
Volume62
Issue number7
DOIs
Publication statusPublished - 2018 Jul

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Salvage Therapy
Amikacin
Respiratory Therapy
Inhalation
Lung Diseases
Macrolides
Sputum
Mycobacterium
Coinfection
Forced Expiratory Volume
Multivariate Analysis
Guidelines
Safety

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Jhun, B. W., Yang, B., Moon, S. M., Lee, H., Park, H. Y., Jeon, K., ... Koh, W. J. (2018). Amikacin inhalation as salvage therapy for refractory nontuberculous mycobacterial lung disease. Antimicrobial agents and chemotherapy, 62(7), [e00011-18]. https://doi.org/10.1128/AAC.00011-18
Jhun, Byung Woo ; Yang, Bumhee ; Moon, Seong Mi ; Lee, Hyun ; Park, Hye Yun ; Jeon, Kyeongman ; Jung Kwon, O. ; Ahn, Jungmin ; Moon, Il Joon ; Shin, Sung Jae ; Daley, Charles L. ; Koh, Won Jung. / Amikacin inhalation as salvage therapy for refractory nontuberculous mycobacterial lung disease. In: Antimicrobial agents and chemotherapy. 2018 ; Vol. 62, No. 7.
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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.",
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Jhun, BW, Yang, B, Moon, SM, Lee, H, Park, HY, Jeon, K, Jung Kwon, O, Ahn, J, Moon, IJ, Shin, SJ, Daley, CL & Koh, WJ 2018, 'Amikacin inhalation as salvage therapy for refractory nontuberculous mycobacterial lung disease', Antimicrobial agents and chemotherapy, vol. 62, no. 7, e00011-18. https://doi.org/10.1128/AAC.00011-18

Amikacin inhalation as salvage therapy for refractory nontuberculous mycobacterial lung disease. / Jhun, Byung Woo; Yang, Bumhee; Moon, Seong Mi; Lee, Hyun; Park, Hye Yun; Jeon, Kyeongman; Jung Kwon, O.; Ahn, Jungmin; Moon, Il Joon; Shin, Sung Jae; Daley, Charles L.; Koh, Won Jung.

In: Antimicrobial agents and chemotherapy, Vol. 62, No. 7, e00011-18, 07.2018.

Research output: Contribution to journalArticle

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AU - Jhun, Byung Woo

AU - Yang, Bumhee

AU - Moon, Seong Mi

AU - Lee, Hyun

AU - Park, Hye Yun

AU - Jeon, Kyeongman

AU - Jung Kwon, O.

AU - Ahn, Jungmin

AU - Moon, Il Joon

AU - Shin, Sung Jae

AU - Daley, Charles L.

AU - Koh, Won Jung

PY - 2018/7

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N2 - 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.

AB - 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.

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