Treatment of Mycobacterium avium–intracellulare complex lung disease in the real world: a retrospective big data analysis

  • Tomohide IwaoEmail author
  • Genta Kato
  • Isao Ito
  • Toyohiro Hirai
  • Tomohiro Kuroda
Original Research Article



The chemotherapeutic regimen recommended by guidelines to prevent the development of a drug-resistant strain of Mycobacterium avium complex (MAC) consists of a combination of clarithromycin, rifampicin, and ethambutol. In severe cases, it is desirable to use either kanamycin or streptomycin in addition to these three drugs. However, it is unclear whether treatment is administered in accordance with the guidelines in real-world clinical settings.


This study aimed to determine the chemotherapy patterns among patients treated for MAC lung disease in medical facilities in Japan.


We investigated treatment patterns regarding patients treated for MAC lung disease between 2007 and 2017, in relation to the latest Japanese guidelines for the treatment of MAC lung disease, using insurance claims data of 378 patients.


The basic triple-agent regimen of clarithromycin, ethambutol, and rifampicin was received by 238 (63%) of the 378 patients. Of these, 115 (48.3%) received the regimen for the recommended period of > 1 year. Therefore, widely publicizing the need for application of standard treatment for at least 2 years is necessary, as is the need to develop methods to overcome adverse effects.


Many patients with MAC lung disease do not complete a full course of treatment over the standard treatment period. Therefore, it is important to develop methods to overcome adverse effects or to develop an alternative treatment regimen for MAC lung disease.



Tomohide Iwao wishes to thank Ms. Shigeko Noguchi for giving the opportunity to conduct this research.

Compliance with ethical standards


This study was undertaken with the help of a research grant from the Japan Society for the Promotion of Science (grant number 17K17816) and the RintyuNet project led by the Japan Agency for Medical Research and Development.

Conflicts of interest

Tomohide Iwao, Genta Kato, Isao Ito, Toyohiro Hirai, and Tomohiro Kuroda declare no conflicts of interest.

Ethical approval

The insurance claims data was obtained from the JMDC in a completely anonymized form, therefore, approval from an Ethics Committee was not required, according to the rules of our organization.


  1. 1.
    Ryu YJ, Koh WJ, Daley CL. Diagnosis and treatment of nontuberculous mycobacteria lung disease: clinicians’ perspectives. Tuberc Respir Dis. 2016;79(2):74–8.CrossRefGoogle Scholar
  2. 2.
    Ho N, Atsuyuki K, Kozo M, et al. Epidemiology of pulmonary nontuberculous mycobacterial disease, Japan. Emerg Infect Dis. 2016;22(6):1116–7.CrossRefGoogle Scholar
  3. 3.
    Adjemian J, Prevots DR, Gallagher J, et al. Lack of adherence to evidence-based treatment guidelines for nontuberculous mycobacterial lung disease. Ann Am Thorac Soc. 2014;11(1):9–16.CrossRefGoogle Scholar
  4. 4.
    van Ingen J, Wagner D, Gallagher J, et al. Poor adherence to management guidelines in nontuberculous mycobacterial pulmonary diseases. Eur Respir J. 2017;49(2):1601855.CrossRefGoogle Scholar
  5. 5.
    The Nontuberculous Mycobacteriosis Control Committee of the Japanese Society for Tuberculosis. The Scientific Assembly for Infection and Tuberculosis of the Japanese Respiratory Society, Guidelines for chemotherapy of pulmonary nontuberculous mycobacterial disease: 2012 revised version in Japanese. Kekkaku. 2013;88(1):29–32Google Scholar
  6. 6.
    Kwon YS, Koh WJ. Diagnosis and treatment of nontuberculous mycobacterial lung disease. J Korean Med Sci. 2016;31(5):649–59.CrossRefGoogle Scholar
  7. 7.
    Griffith DE, Aksamit T, Brown-Elliot BA, et al. An Official ATS/IDSA Statement: diagnosis, treatment and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175(4):367–416.CrossRefGoogle Scholar
  8. 8.
    Schlossberg DL, editor. Tuberculosis and nontuberculous mycobacterial infections. 7th ed. New York: ASM Press; 2017.Google Scholar
  9. 9.
    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):ii1–64.CrossRefGoogle Scholar
  10. 10.
    Yoshihiro K, Toshiharu M. The microbiological and clinical effects of combined therapy according to guidelines on the treatment of pulmonary Mycobacterium avium complex disease in Japan-including a follow-up study. Respiration. 2007;74(4):394–400.CrossRefGoogle Scholar
  11. 11.
    Owusu-Edusei K, Marks SM, Miramontes R, et al. Tuberculosis hospitalization expenditures per patient from private health insurance claims data, 2010–2014. Int J Tuberc Lung Dis. 2017;21(4):398–404.CrossRefGoogle Scholar
  12. 12.
    Japan Medical Data Center. JMDC Claims Database. Accessed 1 May 2019
  13. 13.
    Katsuhiro K, Toshiaki T. Clinical features and treatment history of clarithromycin resistance in M. avium-intracellulare complex pulmonary disease patients (in Japanese). Ann Jpn Resp Soc. 2007;45(8):587–92.Google Scholar
  14. 14.
    Meier A, Kirschner P, Springer B, et al. Identification of mutations in 23S rRNA gene of clarithromycin-resistant Mycobacterium intracellulare. Antimicrob Agents Chemother. 1994;38(2):381–4.CrossRefGoogle Scholar
  15. 15.
    Yano H, Iwamoto T, Nishiuchi Y, et al. Population structure and local adaptation of MAC lung disease agent Mycobacterium avium subsp. hominissuis. Genome Biol Evol. 2017;9(9):2403–17.CrossRefGoogle Scholar
  16. 16.
    Griffith DE, Brown-Elliot BA, Langsjoen B, et al. Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2006;174(8):928–34.CrossRefGoogle Scholar
  17. 17.
    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(1):130–8.CrossRefGoogle Scholar
  18. 18.
    Morimoto K, Iwai K, Uchimura K, et al. A steady increase in nontuberculous mycobacteriosis mortality and estimated prevalence in Japan. Ann Am Thorac Soc. 2014;11(1):487–90.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Medical Information Technology and Administration PlanningKyoto University HospitalKyotoJapan
  2. 2.Solutions Center for Health Insurance Claims, Kyoto University HospitalKyotoJapan
  3. 3.Department of Respiratory Medicine, Graduate School of MedicineKyoto UniversityKyotoJapan

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