Outcomes of Inhaled Amikacin and Clofazimine-Containing Regimens for Treatment of Refractory Mycobacterium avium Complex Pulmonary Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Patients
2.2. Inhaled AMK and CFZ Therapy
2.3. Assessment of Symptomatic, Radiological, and Microbiological Response
2.4. Evaluation of Treatment Outcomes
2.5. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Antibiotic Treatment Regimens
3.3. Treatment Response of Study Patients
3.4. Adverse Effects Associated with Inhaled AMK and CFZ
3.5. Factors Associated with a Favorable Outcome
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Characteristics | Value |
---|---|
Age, years | 59 (51–70) |
Female | 25 (48%) |
Body mass index, kg/m2 | 20.7 (18.3–22.2) |
Weight, kg | 54 (48–62) |
Never-smoker | 29 (56%) |
Underlying condition | |
Previous pulmonary tuberculosis | 27 (52%) |
Chronic pulmonary aspergillosis | 17 (33%) |
Chronic obstructive pulmonary disease | 14 (27%) |
Previous lung cancer * | 3 (6%) |
Diabetes mellitus | 4 (8%) |
Chronic liver disease | 2 (4%) |
Chronic kidney disease | 1 (2%) |
Rheumatoid disease | 1 (2%) |
Other malignancy † | 2 (4%) |
Etiologic organism | |
M. intracellulare | 35 (67%) |
M. avium | 17 (33%) |
Radiologic findings | |
Nodular bronchiectatic form | 27 (52%) |
With cavity | 10/27 (37%) |
Without cavity | 17/27 (63%) |
Fibrocavitary form | 25 (48%) |
Laboratory findings | |
Sputum AFB smear positivity | 34 (65%) |
Serum albumin, g/dL | 4.1 (3.8–4.4) |
C-reactive protein, mg/dL | 0.6 (0.1–1.7) |
Erythrocyte sedimentation rate, mm/h | 30.0 (18.0–67.3) |
FEV1, % | 68 (53–81) |
FVC, % | 74 (56–90) |
Macrolide resistance, ≥32 μ/mL | 25 (48%) |
MIC level of AMK | 16 (16–32) |
4–16 μg/mL | 37 (71%) |
32 μg/mL | 15 (29%) |
Variables | N = 52 | Treatment Duration (Months) |
---|---|---|
Drugs before starting inhaled AMK and CFZ therapy | ||
Azithromycin | 52 (100%) | 27.0 (19.0–56.0) |
Ethambutol | 52 (100%) | 27.0 (16.0–56.0) |
Rifamycin | 50 (96%) | 28.0 (19.0–56.0) |
Moxifloxacin | 13 (25%) | 12.0 (6.0–16.0) |
Aminoglycoside injection | 30 (58%) | 7.0 (5.5–12.0) |
AMK | 2 (4%) | 3.0, 8.0 |
Streptomycin | 28 (54%) | 7.0 (6.0–12.0) |
Total duration before starting AMK and CFZ therapy | 52 (100%) | 28.5 (20.3–55.5) |
Inhaled AMK and CFZ therapy | ||
Total duration of inhaled AMK and CFZ | 52 (100%) | 11.9 (4.7–18.8) |
≥12 months | 27/52 (52%) | 18.7 (12.6–26.4) |
<12 months | 25/52 (48%) | 4.6 (1.2–6.6) |
Total duration of inhaled AMK | 52 (100%) | 12.9 (7.2–20.6) |
Total duration of CFZ | 52 (100%) | 12.5 (5.5–18.9) |
Companion drugs used with inhaled AMK and CFZ | ||
Azithromycin | 51 (98%) | 15.4 (12.4–20.9) |
Ethambutol | 50 (96%) | 16.3 (12.7–22.2) |
Rifamycin | 11 (21%) | 4.0 (3.0–13.0) |
Moxifloxacin | 10 (19%) | 8.5 (3.0–14.2) |
Linezolid | 1 (2%) | 12.4 |
Total duration after starting AMK and CFZ therapy | 52 (100%) | 15.4 (12.5–21.2) |
Variables | N = 52 |
---|---|
Symptomatic response by CAT score change | |
Improved | 25 (48%) |
Unchanged | 11 (21%) |
Worsened | 16 (31%) |
Radiological response | |
Improved | 17 (33%) |
Unchanged | 20 (39%) |
Worsened | 15 (29%) |
Microbiological response | |
At least one sputum negative culture | 22 (42%) |
Time to at least one culture negative, months | 5.1 (1.0–10.1) |
Culture conversion | 17 (33%) |
Time to culture conversion, months | 3.0 (1.0–9.2) |
Microbiological cure | 12 (23%) |
Cure | 6 (12%) |
Clinical cure | 3 (6%) |
Favorable outcome | 15 (29%) |
Microbiological response in ≥12 months treatment group (n = 27) | |
Culture conversion | 10/27 (37%) |
Time to culture conversion, months | 3.0 (0.9–9.3) |
Microbiological cure | 7/27 (26%) |
Cure | 2/27 (7%) |
Clinical cure | 0/27 (0%) |
Microbiological response in <12 months treatment group (n = 25) | |
Culture conversion | 7/25 (28%) |
Time to culture conversion, months | 3.0 (1.0–9.7) |
Microbiological cure | 5/25 (20%) |
Cure | 4/25 (16%) |
Clinical cure | 3/25 (12%) |
Death * | 6 (12%) |
Time from starting inhaled AMK and CFZ to death, months | 11.1 (5.8–20.5) |
Discontinuation | Dose Change | Total | |
---|---|---|---|
Amikacin inhalation | |||
Ototoxicity | 12 (23%) | 5 (10%) | 17 (33%) |
Fatigue | 2 (4%) | 0 (0%) | 2 (4%) |
Tinnitus | 1 (2%) | 0 (0%) | 1 (2%) |
Dizziness | 1 (2%) | 0 (0%) | 1 (2%) |
Nausea | 1 (2%) | 0 (0%) | 1 (2%) |
Hoarseness | 0 (0%) | 1 (2%) | 1 (2%) |
Nephrotoxicity | 0 (0%) | 1 (2%) | 1 (2%) |
Total | 17 (33%) * | 7 (14%) † | 24 (46%) |
Clofazimine | |||
Skin color change | 1 (2%) | 9 (17%) | 10 (19%) |
Loss of appetite | 1 (2%) | 0 (0%) | 2 (4%) |
Diarrhea | 0 (0%) | 1 (2%) | 1 (2%) |
Fatigue | 1 (2%) | 0 (0%) | 1 (2%) |
Hepatotoxicity (>3 times the normal level) | 1 (2%) | 0 (0%) | 1 (2%) |
Total | 4 (8%) ‡ | 10 (19%) | 14 (27%) |
Variable | Favorable Outcome * (n = 15) | Univariable | Multivariable | ||
---|---|---|---|---|---|
Unadjusted OR (95% CI) | p Value | Adjusted OR (95% CI) | p Value | ||
Age ≤ 65 years | 2 (13%) | 4.432 (0.871–22.550) | 0.073 | ||
Female | 9 (60%) | 1.969 (0.581–6.673) | 0.277 | ||
Body mass index, kg/m2 | 1.058 (0.857–1.308) | 0.599 | |||
Never-smoker | 10 (67%) | 1.895 (0.542–6.628) | 0.317 | ||
No previous pulmonary tuberculosis | 8 (53%) | 1.345 (0.404–4.477) | 0.630 | ||
No chronic obstructive pulmonary disease | 14 (93%) | 7.583 (0.894–64.331) | 0.063 | ||
M. avium (reference: M. intracellulare) | 8 (53%) | 3.556 (1.006–12.562) | 0.049 | ||
Negative sputum AFB smear | 6 (40%) | 1.389 (0.401–4.806) | 0.604 | ||
No cavity | 7 (47%) | 2.362 (0.679–8.222) | 0.177 | ||
No macrolide resistance | 8 (53%) | 1.083 (0.325–3.602) | 0.897 | ||
Amikacin MIC < 32 μg/mL | 11 (73%) | 1.163 (0.303–4.461) | 0.825 | ||
Treatment duration ≥12 months | 10 (67%) | 2.353 (0.672–8.239) | 0.181 | ||
FEV1 > 60% | 14 (93%) | 9.545 (1.132–80.506) | 0.038 | ||
ESR, mm/h † | 0.950 (0.914–0.988) | 0.010 | 0.950 (0.914–0.988) | 0.010 | |
CRP, mg/dL † | 0.228 (0.057–0.904) | 0.035 |
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Kim, B.-G.; Kim, H.; Kwon, O.J.; Huh, H.J.; Lee, N.Y.; Baek, S.-Y.; Sohn, I.; Jhun, B.W. Outcomes of Inhaled Amikacin and Clofazimine-Containing Regimens for Treatment of Refractory Mycobacterium avium Complex Pulmonary Disease. J. Clin. Med. 2020, 9, 2968. https://doi.org/10.3390/jcm9092968
Kim B-G, Kim H, Kwon OJ, Huh HJ, Lee NY, Baek S-Y, Sohn I, Jhun BW. Outcomes of Inhaled Amikacin and Clofazimine-Containing Regimens for Treatment of Refractory Mycobacterium avium Complex Pulmonary Disease. Journal of Clinical Medicine. 2020; 9(9):2968. https://doi.org/10.3390/jcm9092968
Chicago/Turabian StyleKim, Bo-Guen, Hojoong Kim, O. Jung Kwon, Hee Jae Huh, Nam Yong Lee, Sun-Young Baek, Insuk Sohn, and Byung Woo Jhun. 2020. "Outcomes of Inhaled Amikacin and Clofazimine-Containing Regimens for Treatment of Refractory Mycobacterium avium Complex Pulmonary Disease" Journal of Clinical Medicine 9, no. 9: 2968. https://doi.org/10.3390/jcm9092968
APA StyleKim, B.-G., Kim, H., Kwon, O. J., Huh, H. J., Lee, N. Y., Baek, S.-Y., Sohn, I., & Jhun, B. W. (2020). Outcomes of Inhaled Amikacin and Clofazimine-Containing Regimens for Treatment of Refractory Mycobacterium avium Complex Pulmonary Disease. Journal of Clinical Medicine, 9(9), 2968. https://doi.org/10.3390/jcm9092968