Treatment of Disseminated MAC

Core Treatment Regimen

The American Thoracic Society recommends treating patients with disseminated MAC who cannot take rifampin with a macrolide (clarithromycin 500 mg twice daily preferred, or azithromycin 500 mg daily as alternative) plus ethambutol 15 mg/kg daily as a two-drug regimen 1, 2, 3
Clarithromycin 500 mg orally twice daily is the preferred macrolide because it clears bacteremia more rapidly than azithromycin in disseminated MAC 1, 2, 3
Azithromycin 500 mg orally once daily is an acceptable alternative if clarithromycin is not tolerated 1, 2, 3
Ethambutol 15 mg/kg orally daily must be included as the mandatory second drug in all disseminated MAC regimens 1, 2, 3

The Infectious Diseases Society of America recommends never using macrolide monotherapy - nearly 50% of patients develop macrolide resistance when treated with a macrolide alone 1, 2
Never exceed clarithromycin 500 mg twice daily - higher doses (1000 mg twice daily) are associated with increased mortality in AIDS patients 1, 3
Obtain baseline macrolide susceptibility testing - if macrolide resistance is present, the regimen must be modified to include amikacin (aminoglycoside) and moxifloxacin (quinolone) 1, 2

The Centers for Disease Control and Prevention recommends continuing treatment lifelong unless immune reconstitution occurs with antiretroviral therapy in HIV patients 1, 2, 3
Discontinue therapy only when all three criteria are met: completion of ≥12 months of MAC treatment, asymptomatic for MAC disease, and CD4 count >100 cells/μL sustained for ≥6 months on HAART 2
Restart treatment if CD4 count drops below 100 cells/μL 2

Perform baseline ECG to assess QTc interval - contraindicate macrolides if QTc >450 ms (men) or >470 ms (women) due to risk of fatal arrhythmias 2, 3
Monitor liver function tests at baseline, 1 month, and every 6 months during macrolide therapy 3
Avoid aluminum/magnesium antacids as they reduce azithromycin absorption when taken simultaneously 2
Common adverse effects of clarithromycin include gastrointestinal symptoms (nausea, vomiting, diarrhea), abnormal liver enzymes, and bitter taste 4
Common adverse effects of azithromycin include gastrointestinal disturbances and QTc prolongation 2

Add amikacin (aminoglycoside) to the regimen if baseline susceptibility testing reveals macrolide resistance, or if the patient develops resistance during therapy 1, 2
Add moxifloxacin (fluoroquinolone) to the regimen if baseline susceptibility testing reveals macrolide resistance, or if the patient develops resistance during therapy 1, 2
Continue ethambutol as part of the multidrug regimen if baseline susceptibility testing reveals macrolide resistance, or if the patient develops resistance during therapy 1, 2
Treatment outcomes are significantly worse with macrolide-resistant strains 1

Never use clofazimine - it is associated with excess mortality in disseminated MAC and should be completely avoided 1, 2, 3
Do not confuse disseminated MAC with pulmonary MAC - disseminated disease requires daily therapy, not the intermittent (three-times-weekly) regimens sometimes used for pulmonary disease 5
Ensure adequate HIV control - successful treatment of disseminated MAC requires treating both the mycobacterial infection and the underlying HIV infection with antiretroviral therapy 1