Mycobacterium avium complex

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Mycobacterium avium complex /
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Microbiology

  • A slow-growing non-tuberculous mycobacterium
  • Comprises M. avium (subspecies hominissuis in humans) and M. intracellulaire
    • 28 serovars between the two
  • Can colonize airways and GI tract as well as causing disease

Differential Diagnosis

  • Pulmonary disease
    • M. kansasii
    • M. abscessus

Epidemiology

  • Common in the environment, likely acquired by inhalation or ingestion (not person-to-person)
    • Water, soil, and animals
    • Natural water, indoor water, pools, hot tubs
  • Risk factors
    • Pulmonary disease: COPD, preior pneumonia, prior TB, steroid use, silicosis, scoliosis, pectus excavatum
    • Disseminated disease: HIV, interferon-gamma defects
    • Cervical lymphadenitis: children 1-5 years old, HIV with IRIS

Pathophysiology

  • In pulmonary disease, likely inhalation ± microaspiration
  • In disseminated disease in AIDS, likely GI colonization then replication and dissemination

Clinical Presentation

Pulmonary disease

  • Incubation months to years
  • Typically presents with non-specific subacute to chronic respiratory syndrome
    • Productive cough, weight loss, fevers, night sweats
  • CXR often shows upper-lobe infiltrates ± cavitations ± pleural thickening
    • Bronchiectasis on CT in 94%
  • Mortality is 15% within 2 to 10 years
  • Specific populations/presentations:
    • Smokers/COPD/alcohol: typical presentation as above
    • Lady Windermere syndrome: slower progression
    • Hot tub lung disease: a hypersensitivity pneumonitis associated with inhalation

Disseminated disease

  • Almost exclusive to HIV patients with CD4 <100
    • Median CD4 was 13
  • Typically presents with high fevers, weight loss, night sweats, anemia
  • Also abdo pain, diarrhea, intraabdo lymphadenopathy, hepatosplenomegaly, and elevated ALP
  • Organ-specific involvement: spleen, lymph nodes, liver, adrenals, stomach, CNS
    • Often not lung involvement
  • Mortality 50% at 4 months

Cervical lymphadenitis

  • Disease of children, usually <3 (80% aged 1 to 5 years)
  • Presents as painless unilateral lymph node enlargement
    • 10% bilateral

Investigations

Pulmonary disease

  • (1) chest radiograph or, in the absence of cavitation, chest high-resolution computed tomography (HRCT) scan
  • (2) three or more sputum specimens for acid-fast bacilli (AFB) analysis
  • (3) exclusion of other disorders, such as tuberculosis

Diagnosis

Pulmonary disease

  • Diagnosis based on presence of both clinical and microbiological evidence
  • Clinical:
    • Pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or an HRCT scan that shows multifocal bronchiectasis with multiple small nodules; and
    • Appropriate exclusion of other diagnoses.
  • Microbiological:
    • Positive cultures from at least two separate expectorated sputum samples; or
    • Positive culture from at least one bronchial wash or lavage; or
    • Transbronchial or other lung biopsy with mycobacterial histopathologic features, and either positive culture for NTM or one or more sputum or BALs positive for NTM

Disseminated disease

  • Diagnosis based on MAC in culture of sterile site

Management

Pulmonary disease

  • Nodular/bronchiectatic disease:
    • Clarithromycin (1,000 mg) or azithromycin (500 mg)
    • Rifampin (600 mg)
    • Ethambutol (25 mg/kg)
    • Three times weekly (because daily never tolerated)
  • If fibrocavitary MAC lung disease or severe nodular/bronchiectatic disease:
    • Clarithromycin (500–1,000 mg) or azithromycin (250 mg) daily
    • Rifampin (600 mg) or rifabutin (150–300 mg) daily
    • Ethambutol (15 mg/kg) daily
    • And consider adding three-times-weekly amikacin or streptomycin early in therapy
  • Duration is until culture negative on therapy for at least 1 year
  • Refer to Ophthalmology for monitoring while on ethambutol

Disseminated disease

  • Antibiotics
    • Clarithromycin (1,000 mg/d) or azithromycin (250 mg/d)
    • Ethambutol (15 mg/kg/d)
    • ± rifabutin (150–350 mg/d)
  • Duration is until resolution of symptoms and reconstitution of cell-mediated immune function (e.g. CD4 >100)

Prophylaxis

  • Indicated for adults with (AIDS) with CD4􏰀 <50; but not done and no longer in the HIV guidelines
  • Antibiotics: azithromycin 1,200 mg/week or clarithromycin 1,000 mg/day
  • Second-line: rifabutin 300 mg/day (less well tolerated)