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. 2024 May;165(5):1058-1069.
doi: 10.1016/j.chest.2023.12.006. Epub 2023 Dec 10.

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

Jennifer H Ku  1 , Emily Henkle  2 , Kathleen F Carlson  3 , Miguel Marino  2 , Sarah K Brode  4 , Theodore K Marras  4 , Kevin L Winthrop  2
Affiliations

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

Jennifer H Ku et al. Chest. 2024 May.

Abstract

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 difficult 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 beneficiaries 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-ethambutol-rifabutin 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.

Keywords: Medicare; Medicare claims; Mycobacterium avium complex; antibiotic therapy; nontuberculous mycobacterial infection.

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Conflict of interest statement

Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: E. H. has served on an advisory board for AN2 pharmaceuticals and received consult fees. K. L. W. has grants or contracts from Insmed; and has received consulting fees from Insmed, Paratek, RedHill Biopharma, Spero Therapeutics, and AN2 pharmaceuticals. T. K. M. has grants or contracts from Insmed, the Centered Outcomes Research Institute, and the Lung Health Foundation; has received consulting fees from Insmed, RedHill Biopharma, and Spero Therapeutics; has received payment or honoraria from France Foundation, Astra Zeneca, Novartis, and Insmed; and has a leadership or fiduciary role in the Toronto NTM patient group. None declared (J. H. K., K. F. C., M. M., S. K. B.).

Figures

None
Graphical abstract
Figure 1
Figure 1
Flow diagram of the analytic population: 4,626 Medicare beneficiaries prescribed a guideline-based three-drug regimen at initial treatment for pulmonary MAC, January 2006 to December 2014. ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification; MAC = Mycobacterium avium complex. ∗Macrolide and one or more other antibiotic drugs targeted for MAC infection: rifamycin (rifampin or rifabutin), ethambutol, fluoroquinolone, or amikacin.
Figure 2
Figure 2
A, Kaplan-Meier curves comparing time to regimen change/discontinuation in azithromycin vs clarithromycin plus ethambutol and rifampin, 2006-2014. B, Kaplan-Meier curves comparing time to regimen change/discontinuation for azithromycin vs clarithromycin plus ethambutol and rifabutin, 2006-2014. MAC = Mycobacterium avium complex.
Figure 3
Figure 3
A, Kaplan-Meier curves comparing time to regimen change/discontinuation for azithromycin, ethambutol plus rifampin vs rifabutin, 2006-2014. B, Kaplan-Meier curves comparing time to regimen change/discontinuation for clarithromycin, ethambutol plus rifampin vs rifabutin, 2006-2014. MAC = Mycobacterium avium complex.
Figure 4
Figure 4
Kaplan-Meier curves comparing time to regimen change/discontinuation for azithromycin-ethambutol-rifampin regimen vs clarithromycin-ethambutol-rifabutin regimen, 2006-2014. MAC = Mycobacterium avium complex.
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