Management of Disseminated MAC with Severe Thrombocytopenia

Introduction to Disseminated MAC Treatment

• The American Thoracic Society recommends clarithromycin 500 mg twice daily (or azithromycin 500 mg daily) plus ethambutol 15 mg/kg daily as the core two-drug regimen for disseminated MAC 1, 2
• Rifabutin at 300 mg/day provided NO additional clinical benefit to the clarithromycin-ethambutol regimen, though it did reduce relapse from macrolide-resistant strains 1

Treatment Considerations

• Clarithromycin and ethambutol have lower hematologic toxicity profiles than rifabutin, making them particularly appropriate for neutropenic or thrombocytopenic patients 1
• The U.S. Public Health Service states that treatment regimens should include at least two agents, with every regimen containing either azithromycin or clarithromycin, and many experts prefer ethambutol as the second drug 3, 4

Monitoring and Precautions

• Obtain baseline macrolide susceptibility testing—if macrolide resistance is present, you must add amikacin and moxifloxacin instead of a rifamycin 1, 2
• Perform baseline ECG to assess QTc interval—contraindicate clarithromycin if QTc >450 ms (men) or >470 ms (women) due to risk of fatal arrhythmias 1, 2
• Never use macrolide monotherapy—nearly 50% of patients develop macrolide resistance when treated with a macrolide alone 1, 2

Additional Considerations

• The British Thoracic Society notes that adverse effects leading to premature discontinuation are more common when the number of drugs in combination is increased 5, 6, 7, 8
• Rifabutin combined with clarithromycin causes significant drug interactions leading to arthralgias, uveitis, neutropenia, and hepatotoxicity 1
• Never add clofazimine—it is associated with excess mortality in disseminated MAC and should be completely avoided 1, 2