What is the recommended treatment regimen for Mycobacterium Avium Complex (MAC)?

Treatment of Mycobacterium Avium Complex (MAC)

For MAC pulmonary disease, treat with a three-drug oral regimen containing a macrolide (preferably azithromycin), rifampin, and ethambutol administered daily, continuing for 12 months after sputum culture conversion to negative. 1, 2

Core Treatment Regimen

Standard Three-Drug Therapy

• Azithromycin is preferred over clarithromycin as the macrolide component 1

  • Azithromycin dosing: 250-500 mg once daily (or 600 mg three times weekly for intermittent regimens) 1, 3
  • Clarithromycin alternative: 500 mg twice daily (maximum 1000 mg/day) 1

• Rifampin 450-600 mg once daily (based on body weight <50 kg vs >50 kg) 1

  • Rifabutin 150-300 mg once daily is an alternative, particularly when drug interactions are a concern 1
  • Critical warning: When combining rifabutin with clarithromycin, use rifabutin at 300 mg/day maximum due to increased risk of uveitis, arthralgias, and neutropenia at higher doses 4, 5

• Ethambutol 15 mg/kg once daily 1

Treatment Duration and Monitoring

• Continue therapy until sputum cultures remain negative for 12 consecutive months while on treatment 2, 6
• Obtain monthly sputum cultures to monitor treatment response 2
• Clinical improvement typically occurs within 3-6 months of starting therapy 2

Disease Severity-Based Approach

Nodular/Bronchiectatic Disease (Non-Cavitary)

• Three-times-weekly intermittent therapy is better tolerated than daily regimens with fewer adverse events 2
• Azithromycin 600 mg, rifampin 600 mg, and ethambutol 25 mg/kg, all three times weekly 1, 2
• Do not use intermittent therapy for cavitary disease, previously treated patients, or moderate-to-severe disease 2, 7

Fibrocavitary or Severe Disease

• Daily regimen is mandatory 7
• Add initial course of intravenous or intramuscular amikacin (10-15 mg/kg daily) or streptomycin (15 mg/kg daily, maximum 1000 mg) for the first 2-3 months 1, 7
• Consider adding amikacin for patients with:
  • AFB smear-positive respiratory samples 1
  • Radiological cavitation or severe infection 1
  • Systemic signs of illness 1

Refractory or Macrolide-Resistant Disease

• Add amikacin liposome inhalation suspension (590 mg daily) or parenteral amikacin for patients whose cultures remain positive after 6 months of guideline-based therapy 7, 6
• Consider adding a fourth agent: levofloxacin or moxifloxacin (400 mg once daily) 1, 7
• Manage in collaboration with NTM experts 1

Critical Treatment Principles

Absolute Contraindications

• Never use macrolide monotherapy - this rapidly induces macrolide resistance 1, 2
• A two-drug regimen (macrolide plus ethambutol only) may be inadequate for fibrocavitary disease due to resistance risk 2, 7

Drug Interactions and Toxicity Monitoring

• Rifabutin-clarithromycin interaction: Rifabutin increases clarithromycin metabolism while clarithromycin increases rifabutin levels, creating bidirectional toxicity risk 5
• Monitor for uveitis (particularly with clarithromycin-rifabutin combination), which occurs in 8-19% of patients 4
• Aminoglycosides cause ototoxicity in approximately one-third of patients after 15 weeks - perform baseline and regular audiometry 7
• Monitor renal function with aminoglycosides and obtain drug levels 1, 7
• Perform monthly vision checks for ethambutol-related ocular toxicity, especially at doses >15 mg/kg/day 1

Special Populations

HIV/AIDS Patients with Disseminated MAC:

• Use clarithromycin 500 mg twice daily (not >1000 mg/day due to excess mortality), ethambutol 15 mg/kg daily, and rifabutin 300 mg daily 1
• Adjust rifabutin dosing for protease inhibitor interactions: 150 mg with strong CYP3A4 inhibitors, 450-600 mg with inducers 1, 5
• Treatment is lifelong unless immune reconstitution occurs (CD4 >100 cells/μL for >12 months) 1

Cystic Fibrosis Patients:

• Use the same antibiotic regimen as non-CF patients 1
• Consider initial IV amikacin for severe presentations 1

Common Pitfalls to Avoid

• Do not use clofazimine in disseminated MAC - it is associated with excess mortality 1
• Avoid clarithromycin doses >500 mg twice daily in HIV patients 1
• Do not discontinue therapy early even if patients feel better - this increases resistance risk 2
• Rifamycins significantly reduce clarithromycin levels, potentially compromising efficacy 1, 5
• When using protease inhibitors with rifabutin, alternative antibacterial therapy should be considered for non-MAC indications due to reduced 14-OH-clarithromycin activity 5