Azithromycin Dosing for Disseminated MAC Infection
For disseminated MAC infection, azithromycin should be dosed at 500 mg orally once daily in combination with ethambutol 15 mg/kg daily, with consideration of adding rifabutin 300 mg daily as a third agent. 1
Core Treatment Regimen
Azithromycin is an alternative to clarithromycin for disseminated MAC, though clarithromycin clears bacteremia more rapidly and is preferred when tolerated. 1 The standard dosing is:
- Azithromycin: 500 mg orally once daily 1
- Ethambutol: 15 mg/kg orally once daily (mandatory second agent) 1
- Rifabutin: 300 mg orally once daily (optional third agent, requires dose adjustment with antiretrovirals) 1
Critical Treatment Principles
Monotherapy is absolutely contraindicated—nearly 50% of patients develop macrolide resistance when treated with a macrolide alone. 1 All patients must receive at least two drugs, with a macrolide as the cornerstone. 1
Macrolides are the only agents for MAC where in vitro susceptibility correlates with clinical response. 1 Baseline susceptibility testing should be performed, and macrolide-resistant strains require alternative regimens including aminoglycosides (amikacin) and quinolones (moxifloxacin). 1
Rifabutin Considerations
The benefit of adding rifabutin as a third drug remains uncertain. 1 Evidence shows:
- At 300 mg/day: No additional clinical benefit but reduced relapse with macrolide-resistant strains 1
- At 450 mg/day: Modest clinical benefit observed 1
Rifabutin combined with clarithromycin causes significant drug interactions leading to arthralgias, uveitis, neutropenia, and hepatotoxicity. 1 If these occur, reduce rifabutin dose or discontinue. 1 Rifabutin also induces cytochrome P-450 and requires dose modifications with protease inhibitors and NNRTIs. 1
Treatment Duration and Monitoring
Treatment should be lifelong unless immune reconstitution occurs with antiretroviral therapy. 1 Discontinuation criteria:
- Completed ≥12 months of MAC treatment 1
- Asymptomatic for MAC 1
- CD4 count >100 cells/μL sustained for ≥6 months on HAART 1
Restart treatment if CD4 count drops below 100 cells/μL. 1
Common Pitfalls
Never use clarithromycin doses above 500 mg twice daily—higher doses are associated with excess mortality in AIDS patients. 1 This makes azithromycin's once-daily 500 mg dosing particularly attractive as it avoids this risk. 1
Avoid clofazimine entirely—it is associated with excess mortality in disseminated MAC. 1
Screen for QTc prolongation before initiating azithromycin, and contraindicate if QTc >450 ms (men) or >470 ms (women). 2, 3 This is especially important given the cardiac risks in immunocompromised patients on multiple medications.
Avoid aluminum/magnesium antacids as they reduce azithromycin absorption when taken simultaneously. 2, 4
Prophylaxis Dosing (Different from Treatment)
For primary MAC prophylaxis in HIV patients with CD4 <50 cells/μL, azithromycin 1,200 mg once weekly is preferred over daily dosing due to lower resistance rates. 1, 4 This prophylactic dose is distinct from the 500 mg daily treatment dose for active disseminated disease. 1, 2, 4
Macrolide-Resistant MAC
For macrolide-resistant strains (MIC ≥32 μg/mL), treatment success is far lower. 1 Consider:
- Amikacin (aminoglycoside) 1
- Moxifloxacin (quinolone) 1
- Consultation with infectious disease specialists 1
Cross-resistance exists between clarithromycin and azithromycin due to 23S rRNA gene mutations. 1 If resistance develops to one macrolide, both are ineffective. 1