Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory Mycobacterium avium Complex Pulmonary Disease

Yu Kurahara; Shiomi Yoshida; Asami Osugi; Yuya Tanaka; Takehiko Kobayashi; Toshiharu Mitsuhashi; Yohei Kawasaki; Satoshi Mitarai; Kazunari Tsuyuguchi

doi:10.1093/ofid/ofaf118

Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory Mycobacterium avium Complex Pulmonary Disease

Open Forum Infect Dis. 2025 Mar 1;12(3):ofaf118. doi: 10.1093/ofid/ofaf118. eCollection 2025 Mar.

Authors

Yu Kurahara^{1

2

3}, Shiomi Yoshida³, Asami Osugi⁴, Yuya Tanaka¹, Takehiko Kobayashi³, Toshiharu Mitsuhashi⁵, Yohei Kawasaki⁶, Satoshi Mitarai⁴, Kazunari Tsuyuguchi^{1

2

3}

Affiliations

¹ Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center, Osaka, Japan.
² Department of Infectious Diseases, NHO Kinki Chuo Chest Medical Center, Osaka, Japan.
³ Clinical Research Center, NHO Kinki Chuo Chest Medical Center, Osaka, Japan.
⁴ Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.
⁵ Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
⁶ Department of Biostatistics, Graduate School of Medicine, Saitama Medical University, Saitama, Japan.

Abstract

Background: Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear.

Methods: We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance.

Results: We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype (P = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ≥1 mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66-70.40) compared with those with CRP <1 mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ≥128 µg/mL), and of these 71.4% (5/7) had rrs mutations.

Conclusions: Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD.

Keywords: Mycobacterium avium complex; amikacin liposome inhalation suspension; amikacin resistance; noncavitary-nodular bronchiectatic; rrs mutation.