What is the treatment for nontuberculous mycobacterial infections?

Treatment of Nontuberculous Mycobacterial Infections

Treatment of nontuberculous mycobacterial (NTM) infections requires species-specific, susceptibility-based antimicrobial regimens rather than empiric therapy, with most regimens including multiple drugs administered for at least 12 months after sputum culture conversion. 1, 2

Diagnosis Confirmation Before Treatment

Before initiating treatment, confirm NTM disease using:

• Clinical symptoms (pulmonary or systemic)
• Radiographic findings (nodular/bronchiectatic or cavitary disease)
• Microbiologic confirmation:
  • ≥2 positive sputum cultures of the same species, or
  • Positive culture from bronchial wash/lavage, or
  • Lung biopsy with histopathologic features and positive culture 1

Species-Specific Treatment Approaches

1. MAC (Mycobacterium avium complex)

• Nodular/bronchiectatic disease:

  • Three-times weekly regimen:
    • Macrolide (azithromycin 500mg or clarithromycin 1000mg)
    • Rifampin 600mg
    • Ethambutol 25mg/kg 1, 2

• Cavitary or severe disease:

  • Daily regimen:
    • Macrolide (azithromycin 250-300mg or clarithromycin 500-1000mg)
    • Rifampin 600mg or rifabutin 150-300mg
    • Ethambutol 15mg/kg
    • Consider adding parenteral amikacin or streptomycin for initial 2-3 months 1, 2

• Macrolide-resistant disease:

  • Include parenteral amikacin/streptomycin
  • Consider adding a fluoroquinolone
  • Consider surgical resection for localized disease 1

• Treatment-refractory disease:

  • Add amikacin liposome inhalation suspension (ALIS) to the regimen 1

2. M. kansasii

• Daily regimen:
  • Rifampin 600mg (test for susceptibility)
  • Ethambutol 15mg/kg
  • Isoniazid 300mg or macrolide 1, 2

3. M. abscessus Complex

• Initial phase (≥4 weeks):

  • Intravenous therapy:
    • Amikacin plus
    • Tigecycline and/or
    • Imipenem and/or
    • Cefoxitin
  • Oral therapy:
    • Macrolide (if susceptible) 1, 2

• Continuation phase:

  • Inhaled amikacin plus
  • 2-4 oral antibiotics based on susceptibility:
    • Macrolide (if susceptible)
    • Clofazimine
    • Linezolid
    • Minocycline/doxycycline
    • Moxifloxacin/ciprofloxacin
    • Co-trimoxazole 2

• Note: For macrolides, perform 14-day incubation and/or sequencing of the erm(41) gene to detect inducible resistance 1

4. M. xenopi

• Multidrug regimen including:
  • Macrolide
  • Rifampin
  • Ethambutol
  • Consider adding moxifloxacin or isoniazid 1

Treatment Duration and Monitoring

• Continue treatment for at least 12 months after sputum culture conversion for all NTM species 1, 2, 3
• Monitor for adverse effects, which are common with NTM treatment regimens:
  • Visual acuity and color discrimination (ethambutol)
  • Audiometry (aminoglycosides)
  • Liver function tests (rifampin, macrolides)
  • Complete blood count (multiple agents) 1, 2

Special Considerations

• Surgical resection: Consider for localized M. abscessus disease or treatment-refractory cases 2
• HIV/AIDS patients with disseminated MAC:
  • Clarithromycin or azithromycin plus ethambutol with or without rifabutin
  • For CD4 <50 cells/μL: prophylaxis with azithromycin 1,200mg weekly or clarithromycin 1,000mg daily 2
• Extrapulmonary NTM infections: Treatment should be tailored to the specific site of infection and causative organism 4

Important Caveats

• NTM treatment is longer than TB treatment, more likely to fail, and more likely to cause toxicity 3
• Treatment varies according to causative organism, drug susceptibilities, radiological type, and disease severity 3
• Meeting diagnostic criteria for NTM pulmonary disease does not necessarily mean antibiotic treatment is required; consider pathogenicity of the organism and risk-benefit assessment 1
• Baseline susceptibility testing is recommended according to CLSI guidelines for all NTM isolates from patients with definite disease 1

Remember that the primary goal of treatment is to improve morbidity, mortality, and quality of life outcomes for patients with NTM infections.