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.
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.
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.
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