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

Treatment of Nontuberculous Mycobacteria (NTM) Infections

For patients with nontuberculous mycobacterial pulmonary disease, treatment should be initiated rather than watchful waiting, especially with positive acid-fast bacilli sputum smears and/or cavitary lung disease. 1

General Treatment Principles

• Treatment decisions should be individualized based on pathogenicity of the organism, risks/benefits of therapy, and patient factors, as meeting diagnostic criteria alone doesn't automatically necessitate treatment 1, 2
• NTM species identification to the species level is essential to guide appropriate therapy 2
• Susceptibility testing is recommended for macrolides in MAC and for rifampin in M. kansasii 1, 2

Species-Specific Treatment Recommendations

Mycobacterium avium complex (MAC)

• A 3-drug regimen that includes a macrolide is strongly recommended for macrolide-susceptible MAC pulmonary disease 1
• Azithromycin is preferred over clarithromycin due to better tolerance, fewer drug interactions, lower pill burden, and single daily dosing 1, 2
• For nodular/bronchiectatic disease:
  • Three-times-weekly regimen of azithromycin/clarithromycin, rifampin, and ethambutol 2
• For cavitary or severe/advanced disease:
  • Daily regimen of azithromycin/clarithromycin, rifampin/rifabutin, and ethambutol 2
  • Consider adding parenteral amikacin or streptomycin in the initial phase for cavitary, advanced/severe bronchiectatic, or macrolide-resistant disease 1, 2

Mycobacterium kansasii

• Daily regimen of isoniazid (300 mg/day), rifampin (600 mg/day), and ethambutol (15 mg/kg/day) 1, 2
• Susceptibility-based treatment for rifampin is recommended 1
• Treatment should continue until cultures remain negative for 1 year 1

Mycobacterium abscessus

• Multidrug regimens including clarithromycin (1,000 mg/day) may provide symptomatic improvement 1
• Susceptibility-based treatment for macrolides and amikacin is recommended 1
• For macrolides, a 14-day incubation and/or sequencing of the erm(41) gene is required to evaluate for potential inducible resistance 1
• Surgical resection of localized disease combined with clarithromycin-based therapy offers the best chance for cure 1, 2

Treatment Duration and Monitoring

• Treatment should generally continue until cultures remain negative for at least 12 months 2
• Close clinical and laboratory monitoring is necessary throughout treatment due to potential medication side effects and drug-drug interactions 2, 3
• Standard therapy for MAC requires approximately 18 months of treatment, with culture conversion rates between 45-70% 4

Treatment of Non-Pulmonary NTM Infections

• Disseminated MAC disease: Therapy should include clarithromycin (1,000 mg/day) or azithromycin (250 mg/day) and ethambutol (15 mg/kg/day) with or without rifabutin (150-350 mg/day) 1
• NTM lymphadenitis: Primarily treated by surgical excision with >90% cure rate; consider macrolide-based regimen for extensive disease or poor response to surgery 1, 2
• Skin and soft tissue infections: Thorough surgical debridement plus culture-directed antibiotic therapy based on susceptibility testing 2

Challenges and Considerations

• Treatment success rates remain suboptimal, with high rates of relapse or reinfection (up to 60% for MAC) 4
• Prolonged treatment duration leads to adherence challenges and medication side effects 2, 3
• Drug-drug interactions are common, especially in elderly patients with comorbidities 2, 3
• A multidisciplinary care team including pharmacy engagement may help increase rates of optimal patient tolerability and successful treatment completion 3

Prophylaxis

• For AIDS patients with CD4 counts <50 cells/μl, prophylaxis with azithromycin 1,200 mg/week or clarithromycin 1,000 mg/day is recommended 1, 2