Tolerability Outcomes of American Thoracic Society/Infectious Diseases Society of America Guideline-Recommended Multidrug Antibiotic Treatment for Mycobacterium avium Complex Pulmonary Disease in US Medicare Beneficiaries With Bronchiectasis

BACKGROUND: Nontuberculous mycobacteria are environmental organisms that are increasingly causing chronic and debilitating pulmonary infections, of which Mycobacterium avium complex (MAC) is the most common pathogen. MAC pulmonary disease (MAC -PD) is often dif fi cult to treat, often requiring long-term multidrug antibiotic therapy. RESEARCH QUESTION: Is there an association between various guideline -based three -drug therapy (GBT) regimens and (1) therapy -associated adverse events or (2) regimen change/ discontinuation, within 12 months of therapy initiation? STUDY DESIGN AND METHODS: In a retrospective cohort study, we examined tolerability outcomes of GBT regimens for MAC -PD in 4,626 US Medicare bene fi ciaries with bronchiectasis, who were prescribed a GBT as initial antibiotic treatment for presumed MAC -PD during 2006 to 2014. Using multivariable Cox proportional hazard regression, we estimated adjusted hazard ratios (aHRs) to compare the risk of adverse events and regimen change/ discontinuations within 12 months of therapy initiation in various GBT regimens. RESULTS: The cohort had a mean age +/- SD of 77.9 +/- 6.1 years at treatment start, were mostly female (77.7%), and were mostly non -Hispanic White (87.2%). The risk of regimen change/ discontinuation within 12 months of therapy was higher for clarithromycin-based regimens than azithromycin-based regimens (aHR, 1.12; 95% CI, 1.04-1.20 with rifampin; aHR, 1.11; 95% CI, 0.93-1.32 with rifabutin as the companion rifamycin), and for rifabutin-containing regimens than rifampin-containing regimens (aHR, 1.49; 95% CI, 1.33-1.68 with azithromycin; aHR, 1.47; 95% CI, 1.27-1.70 with clarithromycin as the companion macrolide). The aHR comparing regimen change/discontinuation with clarithromycin-ethambutolrifabutin and azithromycin-ethambutol-rifampin was 1.64 (95% CI, 1.43-1.64). INTERPRETATION: Overall, an azithromycin-based regimen was less likely to be changed or discontinued than a clarithromycin-based regimen, and a rifampin-containing regimen was less likely to be changed or discontinued than a rifabutin-containing regimen within 12 months of therapy start. Our work provides a population -based assessment on the tolerability of multidrug antibiotic regimens used for the treatment of MAC -PD.