Comparison of Two- Versus Three-antibiotic Therapy for Pulmonary Mycobacterium Avium Complex Disease

Mycobacterium avium complex (MAC) are a subset of nontuberculous mycobacteria (NTM),
environmental bacteria that can cause chronic, debilitating pulmonary disease, primarily
affecting those over age 60. The goals of treatment are to improve symptoms, stop disease
progression, and clear the infection. We propose to address a longstanding controversy in the
therapy of pulmonary MAC disease, whether patients must take three antibiotics concomitantly,
or if two are sufficient. The study is a multicenter randomized pragmatic clinical trial to
compare azithromycin + ethambutol (2-drug therapy) vs. azithromycin + ethambutol + rifampin
(3-drug therapy) for non-cavitary pulmonary MAC disease. All clinical outcomes will be
considered standard of care and abstracted from clinical records. Therapy changes and adverse
events will be recorded at routine visits. Health-related quality of life (HRQoL) and
self-reported toxicity will be captured centrally in a web-based database, and CT scans will
be read centrally. Co-primary outcomes are culture conversion and tolerability of treatment.
The primary analysis for culture conversion will be conducted as a per-protocol
non-inferiority analysis, and the primary analysis for tolerability will be conducted as an
intention-to-treat superiority analysis.

Inclusion Criteria:

- Culture positive pulmonary MAC meeting ATS/IDSA disease criteria

- Age over 18 years

- Ability to provide informed consent

Exclusion Criteria:

- Fibrocavitary disease

- Planned surgery for MAC disease

- Prior multi-drug therapy for pulmonary NTM

- Cystic fibrosis

- HIV

- History of solid organ or hematologic transplant

- Significant drug-drug interaction not clinically manageable in the opinion of the
investigator

- Contraindication to any component of the study treatment regimen