What is the recommended treatment for a lung transplant patient with a new culture from the new lung growing Mycobacterium Avium Complex (MAC)?

Treatment of MAC in Recent Lung Transplant Recipients

For a recent lung transplant recipient with a new culture growing Mycobacterium Avium Complex (MAC) from the transplanted lung, a daily regimen of clarithromycin (500-1000 mg/day) or azithromycin (250 mg/day), rifampin (600 mg) or rifabutin (150-300 mg), and ethambutol (15 mg/kg) with consideration of adding amikacin or streptomycin early in therapy is strongly recommended. 1

Treatment Regimen Details

First-line Therapy:

• Macrolide: Clarithromycin 500-1000 mg daily OR Azithromycin 250 mg daily
• Rifamycin: Rifampin 600 mg daily OR Rifabutin 150-300 mg daily
• Ethambutol: 15 mg/kg daily
• Consider adding: Amikacin or streptomycin (parenteral) for the first 2-3 months, especially given the immunosuppressed status of the transplant recipient

Important Considerations for Lung Transplant Recipients:

1. Daily therapy preferred over intermittent therapy:

   • While intermittent (three-times-weekly) therapy may be acceptable for nodular/bronchiectatic MAC in immunocompetent patients, daily therapy is preferred for immunosuppressed patients including transplant recipients 1
   • The severity of disease in a transplant setting warrants more aggressive treatment

2. Drug interactions:

   • Careful monitoring of immunosuppressant levels is essential due to significant interactions between rifamycins and calcineurin inhibitors
   • Clarithromycin may increase levels of tacrolimus and cyclosporine through CYP3A inhibition 2
   • Rifampin and rifabutin can significantly decrease levels of immunosuppressants through CYP3A induction 2

3. Treatment duration:

   • Treatment should continue until cultures remain negative for at least 12 months 1
   • Monthly sputum cultures should be obtained to monitor treatment response 1

4. Monitoring:

   • Monthly sputum AFB smears and cultures to assess response
   • Patients should show clinical improvement within 3-6 months
   • Sputum conversion to negative should occur within 12 months 1

Special Considerations for Transplant Recipients

• Immunosuppression management: May need adjustment of immunosuppressive medications due to drug interactions
• Enhanced monitoring: More frequent monitoring of drug levels and side effects is warranted
• Susceptibility testing: Clarithromycin susceptibility testing should be performed 1
• Risk of rejection: Monitor for signs of allograft rejection, which may be complicated by infection and treatment

Management of Treatment Failure

If the patient fails to respond to first-line therapy (defined as persistent positive cultures after 6 months):

1. Check for medication adherence and drug interactions
2. Test for macrolide resistance
3. Consider surgical resection if disease is localized and patient is a candidate
4. Consider alternative regimens including:
   • Addition of a fluoroquinolone (moxifloxacin)
   • Addition of clofazimine
   • Addition of bedaquiline (in consultation with experts)
   • Amikacin liposome inhalation suspension for refractory disease 1, 3

Pitfalls and Caveats

• Never use macrolide monotherapy due to high risk of developing resistance 1
• Avoid intermittent therapy in transplant recipients due to immunosuppression 1
• Monitor closely for drug toxicities, especially ethambutol (ocular toxicity) and aminoglycosides (ototoxicity, nephrotoxicity)
• Be vigilant about drug interactions between antimycobacterial drugs and immunosuppressants
• Do not discontinue therapy prematurely before achieving 12 months of negative cultures 1

The treatment of MAC in lung transplant recipients is challenging but essential to prevent graft dysfunction and systemic dissemination. Early, aggressive, and prolonged therapy offers the best chance for successful eradication of the infection.