Mycobacterium avium complex

Background

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, prior 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 Manifestations

Pulmonary Disease

• Incubation period 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)

Dosing

Disease	Drugs	Preferred Regimen	Daily Dose	Thrice-Weekly Dose
Nodular-bronchiectatic	3	azithromycin, or	250-500 mg	500 mg
		clarithromycin; and	500 mg bid	N/A
		rifampin, or	450-600 mg (10 mg/kg)	600 mg
		rifabutin; and	150-300 mg (150 mg if with clarithromycin)	300 mg
		ethambutol	15 mg/kg	25 mg/kg
Cavitary	3+	azithromycin, or	250-500 mg	500 mg
		clarithromycin; and	500 mg bid	N/A
		rifampin, or	450-600 mg (10 mg/kg)	600 mg
		rifabutin; and	150-300 mg (150 mg if with clarithromycin)	300 mg
		ethambutol; and consider	15 mg/kg	25 mg/kg
		amikacin IV	10-15 mg/kg	15-25 mg/kg
Salvage		liposomal inhaled amikacin	590 mg
		clofazimine	100 mg

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)

Further Reading

• Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020 Jul 7;56(1):2000535. doi: 10.1183/13993003.00535-2020. PMID: 32636299; PMCID: PMC8375621.