What is MAI (Mycobacterium Avium-Intracellulare)?

Mycobacterium Avium-Intracellulare (MAI): Definition and Clinical Significance

MAI (also known as MAC or Mycobacterium Avium Complex) is a group of environmental mycobacteria that includes at least two species, M. avium and M. intracellulare, which can cause progressive pulmonary disease, disseminated infection in immunocompromised patients, and other clinical syndromes. 1

Organism Characteristics

• MAI consists of two primary mycobacterial species:

  • M. avium: More commonly associated with disseminated disease, especially in AIDS patients
  • M. intracellulare: More commonly associated with respiratory disease 1

• These species cannot be differentiated using traditional physical and biochemical tests, requiring specific DNA probes for identification 1

• MAI organisms are slow-growing, non-tuberculous mycobacteria (NTM) that take more than 7 days to form visible colonies on culture media 1

Environmental Distribution and Transmission

• MAI organisms are ubiquitous in the environment:

  • Found in soil, water (including natural water sources, indoor water systems, pools, hot tubs)
  • Present in animals and birds 1

• Transmission occurs primarily through environmental exposure:

  • Inhalation or aspiration (pulmonary disease)
  • Ingestion (gastrointestinal colonization leading to potential dissemination)
  • Direct inoculation through trauma (cutaneous disease) 1

• Person-to-person transmission has not been documented 1

Clinical Presentations

1. Pulmonary Disease

MAI pulmonary disease presents in two main forms:

• Fibrocavitary Form:

  • Typically affects middle-aged men (40s-50s) with history of smoking and alcohol use
  • Presents with apical cavitary disease similar to tuberculosis
  • Progressive disease that can lead to extensive lung destruction within 1-2 years if untreated 1, 2

• Nodular/Bronchiectatic Form (Lady Windermere syndrome):

  • Predominantly affects postmenopausal, non-smoking women
  • Characterized by nodular infiltrates and bronchiectasis, often in middle lobe and lingula
  • Generally more indolent course 1, 2

• Common symptoms include:

  • Chronic cough (present in virtually all patients)
  • Sputum production
  • Fatigue and malaise
  • Dyspnea
  • Fever
  • Hemoptysis
  • Weight loss 1

2. Disseminated Disease

• Primarily occurs in severely immunocompromised patients, especially those with advanced HIV (CD4 count <50 cells/μL) 1

• Clinical manifestations include:

  • Fever (80%)
  • Night sweats (35%)
  • Weight loss (25%)
  • Abdominal pain
  • Diarrhea
  • Laboratory abnormalities: severe anemia, elevated alkaline phosphatase, elevated lactate dehydrogenase 1

• Can involve multiple organ systems including liver, spleen, bone marrow, and lymph nodes 1

3. Other Clinical Presentations

• Lymphadenitis: Particularly cervical lymphadenitis in children
• Skin and soft tissue infections: Following direct inoculation
• Skeletal infections: Including spondylodiscitis and epidural abscess 3
• Central nervous system involvement: Rare but can cause meningoencephalitis 4

Diagnosis

1. Microbiological diagnosis:

   • Acid-fast bacilli (AFB) smears and cultures from respiratory specimens (sputum, bronchial washings)
   • Cultures should be performed using both solid and liquid media 1
   • Oro-pharyngeal swabs should not be used for diagnosis 1

2. Diagnostic criteria for pulmonary disease requires:

   • Compatible clinical and radiographic presentation
   • Exclusion of other diagnoses
   • Positive culture results from at least two separate sputum samples or one bronchial wash/lavage 1

3. Species identification:

   • DNA probes can differentiate between M. avium and M. intracellulare
   • This differentiation may have prognostic implications as M. intracellulare lung disease tends to be more severe with worse outcomes 5

Treatment

Treatment depends on the clinical presentation and disease severity:

Pulmonary Disease:

• Macrolide-based multidrug therapy is the cornerstone of treatment:

  • Clarithromycin or azithromycin (macrolide)
  • Ethambutol
  • Rifampin or rifabutin 1, 6

• Treatment should continue for at least 12 months after sputum culture conversion 1

• Surgical resection may be considered for localized disease not responding to medical therapy 1

Disseminated Disease:

• Combination therapy with:

  • Clarithromycin or azithromycin
  • Ethambutol
  • Rifabutin 1, 6

• Treatment duration is typically prolonged (12-24 months) 3

Clinical Significance and Prognosis

• M. intracellulare tends to cause more severe disease with worse outcomes compared to M. avium 5

• Factors associated with poor prognosis include:

  • Fibrocavitary disease
  • Extensive radiographic involvement
  • Smear-positive sputum
  • Older age
  • Low BMI
  • Comorbid conditions 1, 5

• Complications can include progressive lung damage, respiratory failure, and development of pulmonary hypertension in advanced disease 2

Important Considerations

• MAI should be distinguished from tuberculosis, as treatment approaches differ significantly 1

• Empiric therapy for suspected NTM lung disease is not recommended; microbiological confirmation is essential 1

• Long-term follow-up with serial sputum cultures is necessary to monitor treatment response 1

• Microbial substitution can occur during treatment, with emergence of other NTM species like M. abscessus, which can be more difficult to treat 7