What is the recommended treatment for Nontuberculous Mycobacteria (NTM) infections?

Treatment of Nontuberculous Mycobacteria (NTM) Infections

The recommended treatment for NTM infections varies by species, with macrolide-based multidrug regimens being the cornerstone of therapy for most common NTM infections, requiring extended treatment until cultures remain negative for at least 12 months. 1

Species-Specific Treatment Recommendations

Mycobacterium avium complex (MAC) Pulmonary Disease

• For nodular/bronchiectatic disease: A three-times-weekly regimen of clarithromycin (1,000 mg) or azithromycin (500 mg), rifampin (600 mg), and ethambutol (25 mg/kg) 1
• For fibrocavitary or severe nodular/bronchiectatic disease: Daily regimen of clarithromycin (500–1,000 mg) or azithromycin (250 mg), rifampin (600 mg) or rifabutin (150–300 mg), and ethambutol (15 mg/kg) with consideration of three-times-weekly amikacin or streptomycin early in therapy 1
• Azithromycin is preferred over clarithromycin due to better tolerance, fewer drug interactions, lower pill burden, and single daily dosing 1
• Treatment should continue until cultures remain negative for 1 year 1

Disseminated MAC Disease

• Therapy should include clarithromycin (1,000 mg/d) or azithromycin (250 mg/d) and ethambutol (15 mg/kg/d) with or without rifabutin (150–350 mg/d) 1
• Treatment can be discontinued with symptom resolution and immune reconstitution 1
• Prophylaxis for AIDS patients with CD4 counts <50 cells/μl using azithromycin 1,200 mg/week or clarithromycin 1,000 mg/day 1

Mycobacterium kansasii Pulmonary Disease

• Daily regimen of isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d) 1
• Treatment should continue until cultures remain negative for 1 year 1
• Susceptibility testing recommended for rifampin only 1

Mycobacterium abscessus Pulmonary Disease

• No drug regimens of proven efficacy exist 1
• Multidrug regimens including clarithromycin (1,000 mg/day) may provide symptomatic improvement 1
• Surgical resection of localized disease combined with clarithromycin-based therapy offers the best chance for cure 1
• Recent evidence suggests dual beta-lactam combinations (such as imipenem with amoxicillin) may be beneficial when added to standard regimens 2

Treatment of Non-Pulmonary NTM Infections

Skin and Soft Tissue Infections

• Thorough surgical debridement is essential 1
• Culture-directed antibiotic therapy based on susceptibility testing 1
• Treatment duration typically 2-4 months for mild disease and 6 months for severe disease 3
• Empirical regimen of clarithromycin and moxifloxacin may be effective while awaiting culture results 4

NTM Lymphadenitis

• Primarily treated by surgical excision with >90% cure rate 1
• Macrolide-based regimen for extensive disease or poor response to surgery 1
• Management options include surgical intervention, medical therapy, or observation 3

Disseminated NTM Disease

• Treatment generally requires 6-12 months after immune restoration 3
• Therapy should be based on susceptibility testing when available 1

Important Considerations

• NTM species should be identified to the species level to guide appropriate therapy 1

• Susceptibility testing recommendations:

  • MAC: Test for clarithromycin only 1
  • M. kansasii: Test for rifampin only 1
  • Rapidly growing mycobacteria (M. fortuitum, M. abscessus, M. chelonae): Test against multiple antibiotics including amikacin, imipenem, doxycycline, fluoroquinolones, sulfonamides, cefoxitin, clarithromycin, linezolid 1

• Meeting diagnostic criteria for NTM disease does not automatically necessitate treatment - consider risks/benefits and disease severity 1

• Treatment success rates remain suboptimal, with culture conversion rates of 45-70% for MAC and high relapse rates up to 60% 5

• Prevention of healthcare-associated NTM infections requires avoiding tap water exposure to surgical wounds, injection sites, and intravenous catheters 1

Challenges and Pitfalls

• NTM infections are increasingly common but often difficult to diagnose and treat 5
• Extended treatment duration (12-18 months) leads to adherence challenges and medication side effects 1, 5
• Drug-drug interactions are common, especially in elderly patients with comorbidities 1
• Close clinical and laboratory monitoring is necessary throughout treatment 1
• Biofilm formation and unique cell wall structure contribute to antibiotic resistance 5, 6
• New therapeutic options are urgently needed, as current regimens have limited efficacy 5