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      Treatment of Mycobacterium avium Complex Pulmonary Disease

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          Abstract

          The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

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          Most cited references57

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          Environmental sources of nontuberculous mycobacteria.

          Nontuberculous mycobacteria (NTM) include over 150 species. The source for human infection is the environment. NTM are normal inhabitants of soil and drinking water. NTM grow and persist in many buildings. They are not contaminants of drinking water, but members of the natural drinking water microbial population. Infection occurs because humans share the same habitats. Because the ecology, antibiotic susceptibility, and virulence of individual species differs, identifying NTM isolates to species is important. Treatment requires multiple antibiotics. NTM patients are innately sensitive to NTM infection, resulting in reinfection. Knowledge of the sources of NTM can reduce exposure to environmental NTM.
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            British Thoracic Society Guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)

            The full guideline for the management of non-tuberculous mycobacterial pulmonary disease is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline.
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              Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study

              Rationale: Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives: To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods: Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as three consecutive monthly MAC-negative sputum cultures by Month 6. Measurements and Main Results: Enrolled patients (ALIS + GBT, n = 224; GBT-alone, n = 112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS + GBT and 10 of 112 (8.9%) with GBT alone (odds ratio, 4.22; 95% confidence interval, 2.08-8.57; P < 0.001). Patients in the ALIS + GBT arm versus GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% confidence interval, 2.00-7.60). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS + GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions: Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by Month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT02344004).
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                Author and article information

                Journal
                Tuberc Respir Dis (Seoul)
                Tuberc Respir Dis (Seoul)
                TRD
                Tuberculosis and Respiratory Diseases
                The Korean Academy of Tuberculosis and Respiratory Diseases
                1738-3536
                2005-6184
                January 2019
                19 December 2018
                : 82
                : 1
                : 15-26
                Affiliations
                [1 ]Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea.
                [2 ]Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
                [3 ]Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, CO, USA.
                Author notes
                Address for correspondence: Won-Jung Koh, M.D. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. Phone: 82-2-3410-3429, Fax: 82-2-3410-3849, wjkoh@ 123456skku.edu
                Address for co-correspondence: Charles L. Daley, M.D. Division of Mycobacterial and Respiratory Infections, National Jewish Health, Room J204, 1400 Jackson Street, Denver, CO 80206, USA. Phone: 1-303-398-1667, Fax: 1-303-398-1780, daleyc@ 123456njhealth.org
                Author information
                https://orcid.org/0000-0001-5121-4488
                https://orcid.org/0000-0002-4756-3527
                https://orcid.org/0000-0003-3324-926X
                Article
                10.4046/trd.2018.0060
                6304322
                30574687
                260e9208-3473-403b-acb1-ddbd9e513885
                Copyright©2019. The Korean Academy of Tuberculosis and Respiratory Diseases

                It is identical to the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/)

                History
                : 23 July 2018
                : 14 August 2018
                : 16 October 2018
                Categories
                Review Article
                Tuberculosis

                Respiratory medicine
                nontuberculous mycobacteria,mycobacterium avium complex,mycobacterium avium,mycobacterium intracellulare,treatment

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