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Treatment strategies with alternative treatment options for patients with Mycobacterium avium complex pulmonary disease

Institution:	1. Department of Respiratory Medicine, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan;2. Department of Respiratory Medicine, Maebashi Red Cross Hospital, Gunma 371-0813, Japan;3. Department of Respiratory Medicine, Shibukawa Medical Center, Gunma 377-0280, Japan;4. Gunma University Graduate School of Health Sciences, Gunma 371-8514, Japan;1. Department of Advanced Medicine for Respiratory Failure, Graduate School of Medicine, Kyoto University, Kyoto, Japan;2. Department of Clinical Laboratory, Kyoto University Hospital, Kyoto, Japan;3. Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan;4. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan;5. Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan;1. Department of Respiratory Medicine, The Jikei University Kashiwa Hospital, Chiba 277-8567, Japan;2. Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan;3. Division of Neurology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan;4. Department of Neurology, The Jikei University Kashiwa Hospital, Chiba 277-8567, Japan;1. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan;2. Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan;3. Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan;4. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Abstract:	Diseases caused by Mycobacterium avium complex (MAC) infection in the lungs are increasing worldwide. The recurrence rate of MAC-pulmonary disease (PD) has been reported to be as high as 25–45%. A significant percentage of recurrences occurs because of reinfection with a new genotype from the environment. A focus on reducing exposure to MAC organisms from the environment is therefore an essential component of the management of this disease as well as standard MAC-PD treatment. A macrolide-containing three-drug regimen is recommended over a two-drug regimen as a standard treatment, and azithromycin is recommended rather than clarithromycin. Both the 2007 and 2020 guidelines recommend a treatment duration of MAC-PD of at least one year after the culture conversion. Previous clinical studies have reported that ethambutol could prevent macrolide resistance. Furthermore, the concomitant use of aminoglycoside, amikacin liposomal inhalation, clofazimine, linezolid, bedaquiline, and fluoroquinolone with modification of guideline-based therapy has been studied.Long-term management of MAC-PD remains challenging because of the discontinuation of multi-drug regimens and the acquisition of macrolide resistance. Moreover, the poor compliance of guideline-based therapy for MAC-PD treatment worldwide is concerning since it causes macrolide resistance.Therefore, in this review, we focus on MAC-PD treatment and summarize various treatment options when standard treatment cannot be maintained, with reference to the latest ATS/ERS/ESCMID/IDSA clinical practice guidelines revised in 2020.

Keywords:	Mycobacterium avium complex Non-tuberculous mycobacteria Macrolide resistance Liposomal amikacin Alternative treatment Mycobacterium avium complex pulmonary disease"} {"#name":"keyword" "$":{"id":"kwrd0040"} "$$":[{"#name":"text" "_":"MAC-PD ethambutol"} {"#name":"keyword" "$":{"id":"kwrd0050"} "$$":[{"#name":"text" "_":"EMB guideline-based therapy"} {"#name":"keyword" "$":{"id":"kwrd0060"} "$$":[{"#name":"text" "_":"GBT nontuberculous mycobacteria"} {"#name":"keyword" "$":{"id":"kwrd0070"} "$$":[{"#name":"text" "_":"NTM American Thoracic Society"} {"#name":"keyword" "$":{"id":"kwrd0080"} "$$":[{"#name":"text" "_":"ATS European Respiratory Society"} {"#name":"keyword" "$":{"id":"kwrd0090"} "$$":[{"#name":"text" "_":"ERS European Society of Clinical Microbiology and Infectious Diseases"} {"#name":"keyword" "$":{"id":"kwrd0100"} "$$":[{"#name":"text" "_":"ESCMID Infectious Diseases Society of America"} {"#name":"keyword" "$":{"id":"kwrd0110"} "$$":[{"#name":"text" "_":"IDSA fibrocavitary"} {"#name":"keyword" "$":{"id":"kwrd0120"} "$$":[{"#name":"text" "_":"FC nodular-bronchiectasis"} {"#name":"keyword" "$":{"id":"kwrd0130"} "$$":[{"#name":"text" "_":"NB clarithromycin"} {"#name":"keyword" "$":{"id":"kwrd0140"} "$$":[{"#name":"text" "_":"CLR azithromycin"} {"#name":"keyword" "$":{"id":"kwrd0150"} "$$":[{"#name":"text" "_":"AZM rifampicin"} {"#name":"keyword" "$":{"id":"kwrd0160"} "$$":[{"#name":"text" "_":"RIF amikacin"} {"#name":"keyword" "$":{"id":"kwrd0170"} "$$":[{"#name":"text" "_":"AMK streptomycin"} {"#name":"keyword" "$":{"id":"kwrd0180"} "$$":[{"#name":"text" "_":"SM amikacin liposome inhalation suspension"} {"#name":"keyword" "$":{"id":"kwrd0190"} "$$":[{"#name":"text" "_":"ALIS British Thoracic Society"} {"#name":"keyword" "$":{"id":"kwrd0200"} "$$":[{"#name":"text" "_":"BTS fluoroquinolones"} {"#name":"keyword" "$":{"id":"kwrd0210"} "$$":[{"#name":"text" "_":"FQs multi-drug resistant"} {"#name":"keyword" "$":{"id":"kwrd0220"} "$$":[{"#name":"text" "_":"MDR
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