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A2596 - Adverse Effects and Tolerability of Azithromycin-Based Multi-Drug Therapy for Pulmonary Mycobacterium Avium Complex Disease
Author Block: G. P. Ranches1, E. Henkle2, K. L. Winthrop3; 1Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, OR, United States, 2Center for Infectious Disease Studies, Oregon Health and Science University, Portland, OR, United States, 3Infectious Diseases, Oregon Health and Science University, Portland, OR, United States.
Rationale
American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines for pulmonary Mycobacterium avium complex (MAC) disease recommend either daily or thrice weekly multi-drug therapy with a macrolide/azalide, rifamycin and ethambutol for 12+ months after the last negative culture. Successful completion of the daily regimen is often limited by adverse effects, resulting in either treatment modification and/or early therapy cessation. There is limited data regarding the tolerability of the commonly prescribed azithromycin-based regimen.
Methods
We reviewed charts and physician notes of patients enrolled the Northwest nontuberculous mycobacteria (NTM) biobank (N=441). We identified a subgroup of patients (N=85) with pulmonary MAC disease enrolled between 2013-present, who were previously initiated on either daily or thrice weekly treatment with azithromycin, ethambutol, and rifampin. Outcomes include therapy tolerability (defined as completing at least twelve months of therapy) and proportion with a regimen modification and/or early therapy cessation (defined as discontinuing therapy prior to 12 months due to adverse events). We also compared outcomes in thrice weekly and daily regimens.
Results
Thirty-six (42%) patients started thrice weekly regimens, 41 (48%) started daily regimens, and eight (9%) started either mixed regimens or were of unknown frequency. Sixty-eight (80%) were women, and the mean ages for the thrice weekly and daily groups were 69.0 and 72.3, respectively. All but three of the patients met the 2007 ATS/IDSA case definition for disease. Eighty-three (98%) patients had nodules and/or bronchiectasis, and 26 (31%) had cavitary disease. Forty-four patients (52%) tolerated at least 12 months of treatment, and fourteen (16%) were tolerating treatment but had not yet completed 12 months. Twenty-seven patients (32%) experienced AE’s that necessitated either therapy modification or early cessation. Of those 27 patients, 14 were on a thrice weekly regimen (39% of all thrice weekly patients), 10 on a daily regimen (24% of all daily patients), and three on either a mixed regimen or were of unknown frequency. Only eight (9%) patients experienced AE’s to azithromycin, of which the majority were gastrointestinal (GI) related. The most common AE’s between all drugs were GI effects (16%), fatigue (8%), vision changes/optic neuritis (5%) and neuropathy (5%).
Conclusion
Azithromycin-based multi-drug regimens were well tolerated by the majority of patients, though one-third of patients modified or discontinued therapy due to AE’s. Interestingly, daily regimens were better tolerated than thrice weekly regimens. Larger prospective studies are needed to confirm our findings.