Abstract
Amikacin liposomal inhalation suspension (ALIS) and injectable streptomycin (SM) are aminoglycosides used in addition to guideline-based therapy (GBT) in patients with Mycobacterium avium complex lung disease (MAC-LD). However, no studies have compared the efficacy of ALIS and injectable SM in patients with refractory MAC-LD. The current study aimed to retrospectively compare the sputum culture conversion rates and the treatment continuation probability of ALIS and injectable SM in patients with refractory MAC-LD. This study included patients with refractory MAC-LD who were diagnosed with MAC-LD at the Department of Respiratory Medicine at Toho University Medical Center Sakura Hospital from April 2010 to May 2023, and who could not achieve negative sputum culture conversion after GBT for at least 6 months resulting in new treatment with ALIS or injectable SM. The medical records of the patients were retrospectively reviewed. Then, the sputum culture conversion rates up to 6 months and the treatment continuation probability up to 6 months between patients receiving ALIS and those receiving injectable SM were compared. Twenty-three patients with MAC-LD were eligible for present study. Eleven patients were treated with ALIS and 12 with injectable SM. Four (36%) patients treated with ALIS and 2 (17%) with injectable SM achieved negative sputum culture conversion, but there was no statistically significant difference between 2 groups (P = .37). The continuation probability up to 6 months of the patients treated with ALIS was significantly higher than that of patients treated with injectable SM (two-tailed log-rank test hazard ratio: 0.058, 95% confidence interval: 0.018–0.185, P = .0001). The most common cause of injectable SM discontinuation was hospital visit difficulty. ALIS and injectable SM had similar sputum culture conversion rates. However, the former had a higher continuation probability than the latter.
Keywords: amikacin liposomal inhalation suspension, comparative study, Mycobacterium avium complex, nontuberculous mycobacteria lung disease, streptomycin
1. Introduction
Amikacin liposomal inhalation suspension (ALIS) is an aminoglycoside antibiotic used for refractory Mycobacterium avium complex lung disease (MAC-LD).[1–4] Only 65.7% of patients with MAC-LD can achieve negative sputum culture conversion after > 12 months of guideline-based therapy (GBT) comprising macrolide, rifamycin, and ethambutol (EB). Approximately 29% of patients with MAC-LD who cannot achieve negative sputum culture conversion after > 6 months of GBT can achieve such an outcome after a 6-month treatment with ALIS.[1] However, ALIS requires a dedicated nebulizer device, and acquiring inhalation technique inhibits drug use. ALIS is associated with reduced side effects such as hearing impairment, vestibular neuropathy, and renal dysfunction, which are commonly observed with aminoglycoside treatment.[4] However, it can cause hoarseness and hypersensitivity pneumonitis, which can interfere with treatment.[1,5] Therefore, it is also important to select patients who are eligible for ALIS.
Streptomycin (SM) is an injectable aminoglycoside used in addition to GBT in patients with MAC-LD who presented with cavities or severe MAC-LD.[6] The use of injectable SM in addition to GBT within first 3 months is associated with a higher negative sputum culture conversion rate in patients with MAC-LD.[7] In addition, 70.9% of patients with cavitary MAC-LD treated with injectable SM for 4 to 5 months could achieve negative sputum conversion.[8] However, treatment continuation is challenging due the need for hospital visits and the evident adverse effects of aminoglycoside.[7,8] The adverse effects of injectable SM include hearing impairment, vertigo, and renal dysfunction, which can be irreversible. Further, as adverse events are more likely to occur with long-term treatment, the treatment duration must be established.
Both ALIS and injectable SM are effective against refractory MAC-LD. However, there are no report comparing these 2 drugs. Therefore, this single-center retrospective cohort study aimed to compare the efficacy and treatment continuation rates of ALIS and injectable SM in patients with refractory MAC-LD.
2. Methods
2.1. Patient selection
This study included patients with refractory MAC-LD who were diagnosed with MAC-LD at the Department of Respiratory Medicine at Toho University Medical Center Sakura Hospital (Sakura, Japan), and who could not achieve negative sputum conversion after GBT for at least 6 months resulting in new treatment with ALIS or injectable SM. MAC-LD was diagnosed according to the official American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) statement.[9]
2.2. Data collection
2.2.1. Characteristics of the participants
The medical records of patients with MAC-LD treated with ALIS or injectable SM from April 1, 2010 to December 31, 2022, were reviewed. Data on age, sex, body mass index, smoking history (Brinckman index), computed tomography scan findings, sputum acid-fast smear, drug susceptibility test for clarithromycin (CAM) or amikacin (AMK), and use of antibacterial drugs until ALIS or SM initiation were collected.
2.2.2. ALIS and SM
Patients treated with ALIS were admitted to the hospital for 7 days to acquire knowledge on the use of ALIS under the guidance of a specialized nurse. The dose of ALIS in all patients was 590 mg/d. Patients treated with injectable SM visited the outpatient clinic at our hospital 3 times a week. The dose of injectable SM was 15 mg/kg/d. SM was injected into the patient’s upper arm muscle by a nurse. Patients receiving injectable SM and ALIS were examined by a physician every other month to assess for therapeutic and adverse effects.
2.2.3. Chest computed tomography scan
All patients underwent chest computed tomography (CT) scan. Chest CT scan findings were assessed by 1 or more respiratory physicians and radiologists specializing in MAC-LD. The patients were classified into the following 3 groups according to the spread of lesions: mild, lesion area confined to 1 lobe of 1 lung; severe, lesion area extending beyond 1 lung; and moderate, lesion area between mild and severe. In addition, the chest CT scan findings were classified based on the presence of bronchiectasis, nodules, and cavities.
2.2.4. Microbiological examination
Treatment efficacy was determined based on negative sputum culture conversion up to 6 months after ALIS or injectable SM initiation. Sputum was cultured for 42 days using mycobacterial growth indicator tube cultures. Sputum samples were collected every 1 to 2 months at the outpatient clinic. Negative sputum culture conversion was defined as the absence of MAC growth or sputum disappearance. Negative sputum culture conversion was defined as the first negative date. For patients with sputum disappearance, negative sputum culture conversion month was defined as the date when sputum culture was ordered in the medical record. Sputum samples collected from patients treated with ALIS were collected a few minutes before ALIS inhalation to reduce the effect of drug residues on the sputum.
2.2.5. Treatment continuation probability
Treatment continuation was evaluated at 6 months after ALIS or injectable SM initiation. If treatment was discontinued for > 2 weeks during the observation period and then resumed, the treatment continuation probability was evaluated at 6 months from the point of treatment resumption. Data on the causes of treatment discontinuation were extracted.
2.3. Statistical analysis
In cases without annotation, data were expressed as mean and standard deviation. The Mann–Whitney U test was used to assess numerical data. The Fisher exact test and the Pearson chi-square test were used to evaluate categorical data and compare 2 independent groups. P values < .05 (2-tailed) indicated statistically significant differences. The treatment continuation probability between the 2 groups was analyzed using the Kaplan–Meier method with a 2-tailed log-rank test. All statistical analyses were performed using the Statistical Package for the Social Sciences software version 21.0 (IBM Corp., Armonk, NY).
3. Result
Table 1 shows the characteristics of the patients. The current study included 23 patients, with 11 and 12 receiving ALIS and injectable SM, respectively. There were no statistically significant differences in terms of the characteristics of the patients. The median age of the patients treated with ALIS was higher than that of patients receiving injectable SM (77.3 [±7.1] vs 70.0 [±11.4]). The ALIS and injectable SM groups predominantly comprised female patients (82% vs 67%), and the 2 groups had a low BMI (17.2 ± 1.8 vs 17.2 ± 2.9 kg/m²). The ALIS group had a significantly higher incidence of bronchial ectasis, nodules, and cavities, indicating lesion spread on CT scan (55% vs 25%), and prevalence of CAM-resistant strains (55% vs 25%) than the injectable SM group. There was no difference in treatment duration upon ALIS and injectable SM initiation. However, the ALIS group had a higher number of patients using azithromycin than the injectable SM group. Meanwhile, the injectable SM group had a higher number of patients using CAM than the ALIS group.
Table 1.
Characteristics of patients with Mycobacterium avium complex disease.
| ALIS group | SM group | P value | |
|---|---|---|---|
| Number of patients | 11 | 12 | |
| Age (years ± SD) | 77.3 ± 7.1 | 70.0 ± 11.4 | .07* |
| Sex (female) (%) | 9 (81) | 8 (67) | .64† |
| BMI (kg/m2 ± SD) | 17.2 ± 1.8 | 17.2 ± 2.9 | .93* |
| BI > 100 (%) | 0 (0) | 3 (25) | .15† |
| Lesion spread on CT scan | .15‡ | ||
| Mild (%) | 0 (0) | 0 (0) | |
| Moderate (%) | 5 (45) | 9 (75) | |
| Severe (%) | 6 (55) | 3 (25) | |
| Features on CT scan | |||
| Bronchial ectasis (%) | 10 (91) | 9 (75) | .59† |
| Nodule (%) | 10 (91) | 9 (75) | .59† |
| Cavity (%) | 8 (72) | 7 (58) | .67† |
| CAM-resistant strains (%) | 6 (55) | 3 (25) | .15‡ |
| AMK-resistant strains (%) | 0 (0) | 0 (0) | |
| Positive acid-fast smear (%) | 3 (27) | 3 (25) | 1.0† |
| Treatment duration until ALIS or SM initiation (months ± SD) | 42 ± 36 | 34 ± 41 | .21* |
| Antibacterial drugs before ALIS or SM initiation | |||
| AZM/EB/RFP/STFX (%) | 1 (9) | 0 | |
| CAM/EB/RFP/STFX (%) | 1 (9) | 4 (33) | |
| AZM/EB/RFP (%) | 4 (45) | 1 (8) | |
| CAM/EB/RFP (%) | 1 (9) | 6 (50) | |
| CAM/EB/STFX (%) | 2 (18) | 0 | |
| AZM/RFP/STFX (%) | 2 (18) | 1 (8) |
ALIS = amikacin liposomal inhalation suspension, AMK = amikacin, AZM = azithromycin, BI = Brinkman index, BMI = body mass index, CAM = clarithromycin, CT = computed tomography, EB = ethambutol, RFP = rifampicin, SD = standard deviation, SM = streptomycin, STFX = sitafloxacin.
P values < .05 indicated statistically significant difference.
Mann–Whitney U test.
Fisher exact test.
Pearson chi-square test.
Figure 1 shows the monthly sputum culture conversion rates over 6 months. Four (36%) patients treated with ALIS and 2 (17%) with injectable SM achieved negative sputum culture conversion, but there was no statistically significant difference between 2 groups (P = .37). In the ALIS and injectable SM groups, the patients achieved negative sputum culture conversion within 3 months of treatment initiation. To evaluate continuation probability up to 6 months, the Kaplan–Meier curves were used to compare the ALIS and injectable SM groups (Fig. 2). The ALIS group had a significantly higher continuation probability up to 6 months than the injectable SM group (2-tailed log-rank hazard ratio [HR]: 0.058, 95% CI: 0.018–0.185, P = .0001).
Figure 1.
Accumulative proportion of patients achieving negative sputum culture conversion each month up to 6 months. Negative sputum culture conversion was defined as absence of Mycobacterium avium complex or sputum disappear. ALIS = amikacin liposomal inhalation suspension, SM = streptomycin. * Fisher’s exact test.
Figure 2.
Kaplan–Meier curves for comparing continuation probability up to 6 months between patients treated with ALIS and those treated with injectable SM. Continuation probability of the patients treated with ALIS was significantly higher than that of patients treated with injectable SM (2-tailed log-rank HR: 0.058, 95% CI: 0.018–0.185, P = .0001). ALIS = amikacin liposomal inhalation suspension, CI = confidence interval, HR = hazard ration, SM = streptomycin.
Table 2 shows the causes of treatment discontinuation within 6 months. Further, 1 (9%) patient in the ALIS group and 11 (92%) in the injectable SM groups discontinued treatment within 6 months. In the ALIS group, 1 (9%) patient discontinued treatment due to adverse effects including hypersensitivity pneumonitis. Moreover, 4 patients in the injectable SM group discontinued their treatment due to adverse effects including vertigo (n = 2, 17%), anorexia (n = 1, 8%), and drug-related fever (n = 1, 8%). In the injectable SM group, the most common cause of treatment discontinuation was hospital visit difficulty (n = 4, 33%). Table 3 shows the profile of patients who achieved negative sputum culture conversion. Four patients in the ALIS group and 2 in the SM group achieved negative sputum culture conversion. In the ALIS group, 2 of 4 patients were aged > 80 years. Meanwhile, 2 patients in the SM group were aged < 80 years. The drug susceptibility test findings did not significantly differ based on the type and duration of MAC-LD treatment between the ALIS and injectable SM groups. However, 2 patients receiving ALIS who presented with severe lesion spread on CT scan and 1 patient with cavities in each group achieved negative sputum culture conversion. All patients achieved negative sputum culture conversion within 3 months. However, ALIS treatment was continued for 6 months in all cases, whereas SM treatment was discontinued within 3 months.
Table 2.
Causes of treatment discontinuation up to 6 months.
| ALIS group (n = 11) | SM group (n = 12) | |
|---|---|---|
| Dizziness (%) | 0 | 2 (17) |
| Loss of appetite (%) | 0 | 1 (8) |
| Drug-related fever (%) | 0 | 1 (8) |
| Hypersensitivity pneumonitis (%) | 1 (9) | 0 |
| Hospital visit difficulties (%) | 0 | 4 (33) |
| Negative sputum culture (%) | 0 | 2 (17) |
| Unknown causes (%) | 0 | 1 (8) |
ALIS = amikacin liposomal inhalation suspension, SM = streptomycin.
Table 3.
Profile of patients who achieved negative sputum culture conversion.
| Patient no. | Age (yr) | Sex | BMI (kg/m2) | Antibacterial drugs before ALIS or SM initiation | Treatment duration until ALIS or SM initiation (months ± SD) | Lesion spread on computed tomography scan | Cavity | CAM-resistant strains | Time to sputum culture negative conversion (months) | Duration of treatment continuation (days) |
|---|---|---|---|---|---|---|---|---|---|---|
| ALIS | ||||||||||
| 1 | 80 | Female | 14.3 | AZM/EB/RFP | 6 mo | Severe | + | Susceptible | 1 | 180 |
| 2 | 67 | Female | 17.9 | CAM/EB/STFX | 4 yr | Moderate | ‐ | Susceptible | 1 | 180 |
| 3 | 86 | Male | 19.7 | CAM/EB/RFP | 3 yr | Moderate | ‐ | Susceptible | 3 | 180 |
| 4 | 77 | Female | 17.9 | AZM/EB/RFP/STFX | 15 mo | Severe | ‐ | Susceptible | 1 | 180 |
| SM | ||||||||||
| 1 | 74 | Female | 23.2 | CAM/EB/RFP/STFX | 4 yr | Moderate | ‐ | Susceptible | 1 | 46 |
| 2 | 72 | Female | 18.3 | CAM/EB/RFP | 6 mo | Moderate | + | Susceptible | 2 | 88 |
ALIS = amikacin liposomal inhalation suspension, AMK = amikacin, AZM = azithromycin, BMI = body mass index, CAM = clarithromycin, EB = ethambutol, RFP = rifampicin, SM = streptomycin, STFX = sitafloxacin.
4. Discussion
To the best of our knowledge, no study has compared ALIS and injectable SM in patients with refractory MAC-LD. This comparison study of ALIS and injectable SM in patients who did not achieve negative sputum culture conversion after ≥ 6 months of GBT obtained 2 results: First, there was no statistically significant difference in the probability of negative sputum culture conversion. Second, ALIS had a higher treatment continuation probability than SM.
ALIS can have selective antimicrobial activity against localized MAC in the lungs by promoting drug delivery to the infected alveolar macrophages.[10] In the COVERT study, a prospective global phase III trial comparing ALIS + GBT and GBT alone, the addition of ALIS to GBT was associated with a significantly higher negative sputum culture conversion rate.[1] Thus, the ATS/ERS/ESCMID/IDSA Guidelines 2020 and the BTS Guidelines 2017 added ALIS as a treatment option for patients with refractory MAC-LD.[6,11] In addition, a retrospective cohort study of the All-Payer Claims Database reported that ALIS is effective in reducing respiratory-related hospitalizations, all-cause hospitalizations, and respiratory-related outpatient office visits. Further, it can reduce disease severity.[12] In addition, based on an integrated analysis of clinical trials, the number required to treat for ALIS is lower than the number required to harm for several side effects. Hence, due to its therapeutic effect, the need to use ALIS outweighs its adverse effects.[13] However, ALIS and injectable SM could not be compared because injectable aminoglycosides were excluded from the GBT.[1] Several reports have revealed the efficacy of injectable SM.[7,8] In a double-blind, randomized, prospective study, which compared injectable SM and placebo, the sputum culture conversion rate of injectable SM was significantly higher than that of placebo.[7] In a retrospective study comparing injectable SM and injectable AMK in cavitary MAC-LD, there were no significant difference in the sputum culture conversion rate and adverse effects between SM and AMK.[8] Our study did not show a statistically significant difference in the negative sputum culture conversion rate between ALIS and injectable SM. The sputum culture conversion rate of patients treated with ALIS in our study and that in the COVERT study was similar (36% vs 29%). In contrast, the sputum culture conversion rate of injectable SM in our study 16.7% was lower than that in previous studies (16.7% vs 71.2%–74.8%).[7,8] We hypothesized that this is attributed to the inclusion of patients with more severe and progressive MAC-LD, since we selected patients who did not achieve negative sputum culture conversion after ≥ 6 months of GBT. Therefore, the efficacy of ALIS is similar to that of injectable SM in patients with refractory MAC-LD.
In our study, ALIS had a higher 6-month treatment continuation probability than injectable SM. The recommended duration of injectable aminoglycosides is 3 to 6 months according to the guidelines.[6] In contrast, ALIS can be used for > 12 months and is associated with a lower incidence of adverse effects.[14] This may be because the serum concentration of AMK is lower with ALIS than with injectable AMK. The reported maximum serum concentration for injectable AMK is 55.30 ± 16.88 μg/mL, whereas the steady-state serum concentration for ALIS in the CONVERT study was 2.32 μg/mL.[1,15] In our study, the treatment discontinuation rates due to adverse effects were 9% in patients treated with ALIS and 33% in those treated with injectable SM. The injectable SM discontinuation rate due to adverse effects in a previous study was 8.7%, which is lower than that in our study.[8] This study included patients who could continue with MAC-LD treatment for > 1 year. Further, patients who discontinued treatment due to early-phase adverse effects were not included. Hence, the adverse effects of injectable SM might have been underestimated. Further studies must be conducted to determine the incidence of adverse effects in patients receiving injectable SM. In our study, 33% of patients treated with injectable SM discontinued treatment due to hospital visit difficulties. In addition, a previous study revealed that 29% of patients did not received injectable SM due to the same reason.[7] Therefore, ALIS can have a higher treatment continuation rate than injectable SM because it does not require hospital visits and has fewer adverse effects.
The current study had several limitations. First, it was retrospective in nature and was conducted at a single-center. Second, since the number of patients treated with ALIS or injectable SM is limited, a larger number of patients might have yielded different results. Third, which is the most important limitation, the evaluation duration was limited to 6 months. Thus, longer treatment continuation rates and adverse effects could not be evaluated. Therefore, in the future, a prospective comparative study with a larger number of patients must be performed to compare the efficacy of ALIS and injectable SM in patients with refractory MAC-LD.
5. Conclusions
ALIS had a higher treatment continuation rate than injectable SM in patients with refractory MAC-LD. However, the 6-month sputum culture conversion rate was similar.
Author contributions
Conceptualization: Hiroki Wakabayashi.
Data curation: Hiroki Wakabayashi, Yusuke Irie.
Formal analysis: Hiroki Wakabayashi.
Investigation: Hiroki Wakabayashi, Yusuke Irie, Daiki Sakai, Yasuo Matsuzawa.
Methodology: Hiroki Wakabayashi, Yasuo Matsuzawa.
Project administration: Kaichi Kaneko.
Writing – original draft: Hiroki Wakabayashi.
Writing – review & editing: Kaichi Kaneko, Yasuo Matsuzawa.
Abbreviations:
- ALIS
- amikacin liposomal inhalation suspension
- AMK
- amikacin
- BMI
- body mass index
- CAM
- clarithromycin
- CT
- computed tomography
- GBT
- guideline-based therapy
- MAC-LD
- Mycobacterium avium complex lung disease
- SM
- streptomycin
This study was approved by the Ethics Committee of Toho University Medical Center Sakura Hospital (approval number: S23058_S23006) and conducted in accordance with the tenets of the Declaration of Helsinki and STROBE criteria of observational studies. Owing to the retrospective nature of this observational study, the need for patient consent was waived. The study details are disclosed on our website, and the potential participants were provided with the opportunity to opt-out.
The authors have no funding and conflicts of interest to disclose.
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
How to cite this article: Wakabayashi H, Kaneko K, Irie Y, Sakai D, Matsuzawa Y. Amikacin liposomal inhalation suspension versus injectable streptomycin in patients with refractory pulmonary Mycobacterium avium complex disease: A single-center, retrospective cohort study. Medicine 2025;104:49(e46238).
Contributor Information
Kaichi Kaneko, Email: ihciakokenak@med.toho-u.ac.jp.
Yusuke Irie, Email: yusuke.irie@med.toho-u.ac.jp.
Daiki Sakai, Email: daiki.sakai@med.toho-u.ac.jp.
Yasuo Matsuzawa, Email: yasuo23@sakura.med.toho-u.ac.jp.
References
- [1].Griffith DE, Eagle G, Thomson R, et al. Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT). A prospective, open-label, randomized study. Am J Respir Crit Care Med. 2018;198:1559–69. [DOI] [PubMed] [Google Scholar]
- [2].Shirley M. Amikacin liposome inhalation suspension: a review in Mycobacterium avium complex lung disease. Drugs. 2019;79:555–62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [3].Khan O, Chaudary N. The use of amikacin liposome inhalation suspension (Arikayce) in the treatment of refractory nontuberculous mycobacterial lung disease in adults. Drug Design Dev Ther. 2020;14:2287–94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [4].Hoy SM. Amikacin liposome inhalation suspension in refractory Mycobacterium avium complex lung disease: a profile of its use. Clin Drug Investig. 2021;41:405–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Griffith DE, Thomson R, Flume PA, et al. Amikacin liposome inhalation suspension for refractory Mycobacterium avium complex lung disease: sustainability and durability of culture conversion and safety of long-term exposure. Chest. 2021;160:831–42. [DOI] [PubMed] [Google Scholar]
- [6].Haworth CS, Banks J, Capstick T, et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017;72(suppl 2):ii1–ii64. [DOI] [PubMed] [Google Scholar]
- [7].Kobashi Y, Matsushima T, Oka M. A double-blind randomized study of aminoglycoside infusion with combined therapy for pulmonary Mycobacterium avium complex disease. Respir Med. 2007;101:130–8. [DOI] [PubMed] [Google Scholar]
- [8].Kim SM, Chong YP, Lee HJ, Shim TS, Jo KW. Comparison of treatment outcomes of cavitary Mycobacterium avium complex pulmonary disease with streptomycin or amikacin use. Microbiol Spectr. 2023;11:e0474122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175:367–416. [DOI] [PubMed] [Google Scholar]
- [10].Zhang J, Leifer F, Rose S, et al. Amikacin liposome inhalation suspension (ALIS) penetrates non-tuberculous mycobacterial biofilms and enhances amikacin uptake into macrophages. Front Microbiol. 2018;9:915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020;56:2000535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12].Aksamit T, Wu J, Hassan M, Achter E, Chatterjee A. Impact of initiation of amikacin liposome inhalation suspension on hospitalizations and other healthcare resource utilization measures: a retrospective cohort study in real-world settings. BMC Pulm Med. 2022;22:461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [13].Marras TK, Hassan M, Mange KC, et al. Amikacin liposome inhalation suspension clinical benefit-risk assessment for refractory Mycobacterium avium complex lung disease. ERJ Open Res. 2022;8:00623–2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [14].Winthrop KL, Flume PA, Thomson R, et al. Amikacin liposome inhalation suspension for Mycobacterium avium complex lung disease: a 12-month open-label extension clinical trial. Ann Am Thorac Soc. 2021;18:1147–57. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].van Ingen J, Egelund EF, Levin A, et al. The pharmacokinetics and pharmacodynamics of pulmonary Mycobacterium avium complex disease treatment. Am J Respir Crit Care Med. 2012;186:559–65. [DOI] [PubMed] [Google Scholar]