@hmap Welcome to Mayo Connect. Thank you for taking the time to oversee your Mom's care and to understand the complexities of treatment for MAC. That is exactly why this forum exists, since MAC is pretty rare, and finding others who have it and can share experience can be difficult.

When I was under treatment with the Big 3, and having trouble tolerating the meds, one of the things the doc considered was changing the rifampin to rifabutin. We finally figured out that the Clarithromycin was the culprit, and I changed to Azithromycin. But...

That led me to doing a lot of studying of the meds and why each choice is made. At the time, I found info about rifampin vs rifabutin and just managed to find my bookmark. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290133/

This is a complex and lengthy analysis, but the bottom line is that rifabutin is often more easily tolerated, it does not stay in the system as long (important if she is taking daily because it will build up in the body), and it has less interactions with other meds, so requires less dosage adjustment and/or monitoring.

Why did the ID doc make the change? He may well be more aware of potential interactions than the pulmonologist because his job is to treat complex and difficult infections. Or he may have noticed something in her bloodwork that led him to make the change.

How is your Mom tolerating the drug regime? Is she also doing daily airway clearance to help clear her lungs?
It might be worth asking the question about rifabutin vs rifampin of the ID doc, just so you have a clear picture of how your Mom's treatment is going.
Sue