Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory

Yu Kurahara1,2,3, Shiomi Yoshida3, Asami Osugi4

  • 1Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center, Osaka, Japan.

PubMed
Abstract

Insights

Amikacin liposome inhalation suspension (ALIS) shows higher efficacy in noncavitary nodular bronchiectatic (NC-NB) compared to cavitary pulmonary disease. Acquired amikacin (AMK) resistance during treatment may limit therapeutic options for refractory Mycobacterium avium complex pulmonary disease (MAC-PD).

Area of Science:

  • Pulmonary Medicine
  • Infectious Diseases
  • Pharmacology

Background:

  • Amikacin liposome inhalation suspension (ALIS) is crucial for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD).
  • Microbiological efficacy of ALIS across different MAC-PD subtypes is not well-established.
  • The emergence and mechanisms of amikacin (AMK) resistance during ALIS therapy require further investigation.

Purpose of the Study:

  • To evaluate the microbiological efficacy of ALIS in patients with refractory MAC-PD, stratified by disease subtype.
  • To determine the frequency and potential mechanisms of AMK resistance developing during ALIS treatment.
  • To identify predictors of treatment response and persistent infection in refractory MAC-PD.

Main Methods:

  • Retrospective analysis of 44 refractory MAC-PD patients treated with ALIS adjunctively for at least 6 months.
  • Investigation of sputum culture conversion rates, focusing on differences between noncavitary nodular bronchiectatic (NC-NB) and cavitary subtypes.
  • Analysis of gene expression and the incidence of AMK resistance (MIC ≥128 µg/mL), including identification of specific mutations (e.g., in *rrs*).

Main Results:

  • Overall sputum culture conversion was 56.8%, with significantly higher rates in the NC-NB subtype (84.2%) compared to the cavitary subtype (36.0%).
  • Patients with high C-reactive protein (CRP), cavitary disease, and clarithromycin (CLM) resistance showed a significantly higher risk of persistent positive cultures.
  • Amikacin resistance was observed in 15.9% of patients, with *rrs* mutations identified in 71.4% of resistant isolates.

Conclusions:

  • ALIS-containing regimens demonstrate superior culture conversion rates in NC-NB MAC-PD compared to cavitary forms.
  • High CRP levels, cavitary disease, and CLM resistance are predictors of persistent microbiological positivity.
  • Acquired AMK resistance during ALIS therapy poses a significant challenge, potentially limiting future treatment options for refractory MAC-PD.