How do you treat Mycobacterium infections that are resistant to standard treatments?

Treatment of Resistant Mycobacterial Infections

For resistant mycobacterial infections, treatment should include multiple drugs based on susceptibility testing, with combinations of rifampicin, ethambutol, macrolides, fluoroquinolones, and injectable agents tailored to the specific mycobacterial species and resistance pattern.

Species-Specific Treatment Approaches

M. kansasii Resistant Infections

• First-line treatment for rifampicin-susceptible M. kansasii:

  • Rifampicin, ethambutol, and either isoniazid or a macrolide for 9-12 months 1
  • Treatment success rates of 95.5% with rifampicin-based regimens 1

• For rifampicin-resistant M. kansasii:

  • Include a fluoroquinolone (e.g., moxifloxacin) as part of a second-line regimen 1
  • Add clarithromycin and consider adding streptomycin or amikacin if needed 1
  • Continue treatment until cultures have been negative for 12 months 1

M. avium Complex (MAC) Resistant Infections

• For refractory MAC disease:
  • Daily regimen of azithromycin (or clarithromycin), rifampicin (or rifabutin), ethambutol, plus amikacin liposome inhalation suspension or injectable amikacin 1
  • Consider adding clofazimine, moxifloxacin, or linezolid for highly resistant cases 1
  • For patients who fail/relapse, continue treatment indefinitely or add ciprofloxacin, clarithromycin, or streptomycin 1
  • Surgical resection for unilateral disease in suitable candidates 1

M. xenopi Resistant Infections

• Treatment regimen:
  • Combination of at least 3 drugs including azithromycin/clarithromycin and/or moxifloxacin, rifampicin, ethambutol, and amikacin 1
  • Treatment for 2 years with ethambutol and rifampicin 1
  • Consider surgery for those who fail to respond and are fit enough 1

Rapidly Growing Mycobacteria (M. abscessus, M. fortuitum, M. chelonae)

• Treatment approach:
  • Surgical debridement when possible 1
  • Combination of rifampicin, ethambutol, and clarithromycin 1
  • Consider adding quinolones, sulfonamides, amikacin, cefoxitin, or imipenem 1
  • For M. abscessus specifically, consider rifabutin with clarithromycin and tigecycline which shows synergistic and bactericidal activity 2

General Principles for Resistant Mycobacterial Infections

1. Drug Susceptibility Testing:

   • Essential for guiding therapy, particularly for rifampicin and ethambutol in M. kansasii 1
   • Standard in vitro testing has limited value for most NTM except for rapidly growing mycobacteria 1

2. Duration of Treatment:

   • Continue treatment until cultures have been negative for at least 12 months 1
   • For M. kansasii: 9-12 months of treatment 1
   • For MAC and M. xenopi: 24 months of treatment 1

3. Monitoring Response:

   • Monthly sputum cultures during initial treatment
   • Regular clinical and radiological follow-up
   • Be vigilant for drug toxicity, particularly with prolonged regimens

4. Surgical Intervention:

   • Consider for localized disease not responding to medical therapy
   • Particularly useful for M. abscessus and unilateral MAC or M. xenopi disease 1

Special Considerations

• HIV Co-infection:

  • May require more aggressive treatment and longer duration
  • Consider therapeutic drug monitoring due to potential malabsorption issues

• Common Pitfalls:

  • Inadequate number of drugs (use at least 3 effective drugs)
  • Insufficient treatment duration
  • Poor adherence leading to further resistance
  • Failure to adjust therapy based on clinical response or drug toxicity

• Treatment Failure Management:

  • Add one or more new drugs from a different class
  • Consider injectable agents if not already used
  • Evaluate for surgical options in suitable candidates
  • For MAC, consider adding bedaquiline or tedizolid in consultation with experts 1

By following these principles and tailoring therapy to the specific mycobacterial species and resistance pattern, successful treatment outcomes can be achieved even in resistant mycobacterial infections.