What are the Non-Tubercular Mycobacteria (NTM) and what are the indicated antibiotics and duration of therapy for each type?

Non-Tuberculous Mycobacteria: Antibiotic Regimens and Treatment Duration

Overview of Major NTM Species

Non-tuberculous mycobacteria (NTM) are a diverse group of environmental mycobacteria that require species-specific multidrug regimens, with treatment continued for a minimum of 12 months after culture conversion. 1, 2

The clinically significant NTM species include:

• Slowly growing mycobacteria: Mycobacterium avium complex (MAC), M. kansasii, M. xenopi
• Rapidly growing mycobacteria: M. abscessus complex, M. fortuitum, M. chelonae 3, 4

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Mycobacterium avium Complex (MAC)

Non-Cavitary/Mild Nodular-Bronchiectatic Disease

• Three-times-weekly oral therapy with:
  • Azithromycin 500-600 mg
  • Rifampin 600 mg
  • Ethambutol 25 mg/kg 1, 2

Fibrocavitary or Severe Nodular-Bronchiectatic Disease

• Daily oral therapy with:

  • Azithromycin 250-500 mg daily (preferred) OR clarithromycin 500 mg twice daily
  • Rifampin 450-600 mg daily OR rifabutin 150-300 mg daily
  • Ethambutol 15 mg/kg daily 5, 1, 2

• Add intravenous amikacin 15 mg/kg daily or three-times-weekly for severe disease with:

  • AFB smear-positive respiratory samples
  • Radiological cavitation or severe infection
  • Systemic signs of illness 5

Duration

• Continue treatment for minimum 12 months after sustained culture conversion (defined as three consecutive negative cultures) 5, 1, 2

Critical Caveat for CF Patients

• Never use intermittent (three-times-weekly) therapy in cystic fibrosis patients—only daily regimens 5
• Never use macrolide monotherapy as this rapidly induces resistance 5, 2

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Mycobacterium abscessus Complex

This is the most difficult NTM to treat, requiring biphasic therapy with intensive and continuation phases. 5

Intensive Phase (3-12 weeks)

• Daily oral macrolide (azithromycin 250-500 mg preferred) 5
• PLUS intravenous amikacin 15 mg/kg daily or three-times-weekly 5
• PLUS one or more of:
  • Intravenous tigecycline 50 mg twice daily
  • Intravenous imipenem 1 g twice daily
  • Intravenous cefoxitin 12 g/day 5

Duration of intensive phase determined by severity, response, and tolerability (minimum 4 weeks for severe disease) 5

Continuation Phase

• Daily oral macrolide (azithromycin 250-500 mg preferred) 5
• PLUS inhaled amikacin 5
• PLUS 2-3 of the following oral agents (guided by susceptibility testing):
  • Clofazimine 50-100 mg daily
  • Linezolid 600 mg once or twice daily
  • Minocycline 100 mg twice daily
  • Moxifloxacin 400 mg daily
  • Co-trimoxazole 960 mg twice daily 5

Duration

• Continue for minimum 12 months after culture conversion 5, 1

Special Considerations

• For constitutive macrolide-resistant isolates: omit macrolide from regimen 5
• Manage in collaboration with NTM experts due to frequent drug intolerance and toxicity 5
• Never use macrolide monotherapy 5, 2

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Mycobacterium kansasii

Rifampin-Sensitive Disease (Most Common)

• Daily oral regimen with:
  • Rifampin 600 mg daily
  • Ethambutol 15 mg/kg daily
  • Isoniazid 300 mg daily OR a macrolide (azithromycin or clarithromycin) 1, 2

Duration

• Continue for minimum 12 months after culture conversion 1

Expected Outcomes

• Rifampin-based regimens achieve 80-100% cure rates with relapse rates of only 2.5-6.6% 1

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Mycobacterium fortuitum

Critical Warning About Macrolides

Do not rely on macrolides despite susceptibility testing showing "susceptible" results—all M. fortuitum isolates contain inducible erm(39) gene conferring macrolide resistance. 1, 2

Treatment Regimen

• Use at least two agents with in vitro activity based on susceptibility testing 1, 2
• Common effective agents include:
  • Fluoroquinolones (moxifloxacin, ciprofloxacin)
  • Sulfonamides (co-trimoxazole)
  • Doxycycline or minocycline
  • Amikacin
  • Imipenem or cefoxitin 3, 6

Duration

• Continue for minimum 12 months after culture conversion 1, 2

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Monitoring Requirements During Treatment

Establish a comprehensive monitoring schedule at treatment initiation and implement throughout therapy: 5, 1, 2

• Audiometry for hearing loss (aminoglycosides, macrolides)
• Visual acuity and color vision testing (ethambutol)
• Renal function (aminoglycosides, rifampin)
• Liver function tests (rifamycins, macrolides, isoniazid)
• Sputum cultures every 4-8 weeks throughout entire treatment course 5, 1, 2
• High-resolution CT shortly before starting treatment and at completion to assess radiological response 5, 1, 2

Aminoglycoside Monitoring

• Monitor serum levels when using intravenous amikacin or streptomycin and adjust dosing to minimize ototoxicity and nephrotoxicity 5

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Critical Pitfalls to Avoid

Never Use Macrolide Monotherapy

The single most critical error is using macrolide monotherapy for any duration, as this rapidly induces resistance and leads to treatment failure. 5, 2, 7

• If a patient on chronic azithromycin (e.g., for CF) develops positive NTM culture, immediately discontinue azithromycin until NTM disease is ruled out 5, 7
• Azithromycin requires 2-week washout period due to intracellular accumulation before collecting diagnostic samples 5

Species Identification is Mandatory

• Obtain species-level identification before initiating treatment, as regimens differ dramatically between organisms 1, 2
• Perform susceptibility testing according to CLSI guidelines prior to treatment 5, 2

Drug Interactions and Tolerability

• Drug-drug interactions are common, especially with rifamycins in elderly patients with comorbidities 2
• Extended treatment duration leads to adherence challenges and medication side effects requiring close monitoring 2

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Non-Pulmonary NTM Infections

Lymphadenitis

• Primary treatment is surgical excision with >90% cure rate 1, 2

Skin and Soft Tissue Infections

• Perform thorough surgical debridement 1, 2
• Use culture-directed antibiotic therapy based on susceptibility testing for minimum 4-6 months 1, 2