This is a prospective observational study using whole genome sequencing (WGS) to investigate whether new strains (other than the initially identified strain(s)) of M. avium are responsible for persistently culture positive sputum during treatment (refractory disease), or the reversion to culture positive sputum after prior conversion to negative. The study will further investigate for differences between participants living in the Toronto/York region versus participants living elsewhere.

The primary goal of this prospective observational study is to understand why some patients with M. avium lung disease have persistent or recurrent M. avium in their sputum despite treatment. The aim is to understand whether it is usually due to treatment failure or new infection.

Mycobacterium Avium complex (MAC) are a subset of nontuberculous mycobacteria (NTM) that are typically found in the soil and water and can cause pulmonary lung disease. Treatment of MAC is challenging as it typically requires the use of three or more antibiotics for over a long period of time and the rate of eradication is suboptimal.

Mac-WGS is an observational study that aims to understand whether new strains of M. avium are responsible for persistently culture-positive sputum during treatment. Whole genome sequencing (WGS) will be performed on M. avium isolates from the sputum of patients with Mav-PD, over the duration of the study. Additionally, home environmental samples will be collected and sequenced to identify any home source of infection.

As an observational study, participants will receive routine standard of care treatment as per discretion of the physician. Standard of care includes monthly sputum submissions. The M. avium isolated from the sputum before treatment and every three months while on treatment (until such time that the sputum becomes culture-negative) will be analyzed by WGS. If sputum becomes culture-positive again, the isolated germ will also be analyzed by whole genome sequencing. It will be determined whether the identical strain of M. avium is always present or whether more than one strain is present which would suggest either multi-strain infection or the acquisition of new strains of M. avium while on treatment. Additionally, participant's home environmental samples (i.e. faucets and showerhead biofilms) will be cultured to determine whether M. avium can be recovered and if so, it will be analyzed with WGS to assess whether it is the same strain as in the participant's sputum.

Inclusion Criteria:

• Age 18 and older
• Willing to provide informed consent and participate in study procedures
• Residing continuously in Ontario during the past five years
• Mav-PD, either initial or recurrent (previously treated patients will be eligible) five years
• Meet American Thoracic Society (ATS) / Infectious Diseases Society of America (IDSA) NTM disease criteria for Mav-PD

Exclusion Criteria:

• Lack of an available pre-treatment M. avium isolate in the PHOL isolate bank
• The inability to produce sputum either spontaneously or by induction with nebulized hypertonic saline
• Cavitation >3 cm internal diameter
• Known macrolide-resistant MAC infection
• HIV infection
• Known diagnosis of cystic fibrosis
• History of solid organ or hematological transplantation
• Severe comorbid illness that is reasonably expected to limit survival to <24 months
• Residing in mid/north York region (King, Aurora, Newmarket, Whitechurch-Stouffville, East Gwillimbury or Georgina)
• Having moved between regions (Toronto/southern York region vs non-Toronto/York region vs mid-northern York region) within the past 5 years

Patients at the Toronto Western Hospital (TWH) Nontuberculous Mycobacterial (NTM) clinic who are to be initiated on therapy for Mav-PD.