About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial population
Patients at the Toronto Western Hospital (TWH) Nontuberculous Mycobacterial (NTM) clinic who are to be initiated on therapy for Mav-PD.
Trial design
Cohort
Prospective
Treatments tested in this trial
Whole genome sequencing testing
Other interventionWhole genome sequencing
Treatment groups
Trial outcomes
Primary outcomes
Proportion of patients with persistent culture-positive sputum despite antimicrobial therapy
Whole genome sequencing
Secondary outcomes
Whether patients with Mav-PD have evidence of polyclonal infection as demonstrated by the presence of >1 strain of M. avium in the pre-treatment sputum or a sputum sample during treatment
Whole genome sequencing
Whether there is a source of infection from the home water environment
M. avium strains from sputum and home water source samples will determined through WGS analysis.
Sponsors and contacts
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University Health Network, Toronto
Lead sponsor
Western University, Canada
Collaborator
Public Health Ontario Laboratory, Canada
Collaborator