Mycobacteria

Epidemiology & Risk Factors

• Environmental organisms: Found in soil, tap water, biofilms; NO person-to-person transmission (respiratory isolation NOT required).
• Pulmonary Risk Factors:
  • Pre-existing structural lung disease: Bronchiectasis, COPD, CF, prior TB infection, alpha-1 antitrypsin deficiency.
  • Lady Windermere Syndrome: Thin, elderly females with voluntary cough suppression → nodular bronchiectasis (MAC in RML/lingula).
• Disseminated Risk Factors:
  • Severe cell-mediated immunodeficiency: Advanced HIV/AIDS (CD4 < 50/mm³), anti-TNF therapy, solid-organ/hematopoietic transplant. c
• Skin/Soft Tissue Risk Factors:
  • M. marinum: Direct exposure to aquariums/fish tanks, saltwater, or non-chlorinated pools.
  • M. abscessus / M. fortuitum: Surgical procedures, cosmetic injections, or tattoo equipment contamination.

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Clinical Features

• Pulmonary NTM (Most common: M. avium complex [MAC], M. kansasii):
  • Insidious onset: Chronic cough, purulent sputum, progressive dyspnea, hemoptysis.
  • Systemic symptoms: Fatigue, low-grade fever, night sweats, weight loss.
• Disseminated MAC (HIV/AIDS w/ CD4 < 50): c
  • High-grade fever, drenching night sweats, profound weight loss, abdominal pain, diarrhea.
  • PE: Hepatosplenomegaly, diffuse peripheral lymphadenopathy.
• Skin/Soft Tissue Disease:
  • M. marinum: Single violaceous nodule/ulcer at trauma site → sporotrichoid spread (nodular lesions ascending along lymphatic drainage).
• Pediatric Lymphadenitis:
  • Subacute, unilateral, painless cervical lymphadenopathy in immunocompetent children aged 1–5 yrs; skin turns violaceous and may fistulize.

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Diagnosis

• Initial Test / Imaging:
  • Pulmonary: HRCT Chest showing bronchiectasis with centrilobular nodules (tree-in-bud pattern) or upper lobe cavitary lesions.
  • Disseminated: Blood culture for AFB (highest sensitivity in CD4 < 50).
• Key Labs:
  • Sputum AFB Stain & Culture: Requires ≥2 separate positive sputum cultures (or 1 positive BAL fluid culture) + clinical/radiologic evidence to differentiate colonization from infection.
  • Disseminated MAC: Marked ↑ Alkaline Phosphatase (ALP), severe anemia, leukopenia.
  • PPD / IGRA: Usually negative or indeterminate for NTM (IGRA is specific for M. tuberculosis).
• Confirmatory / Gold Standard:
  • Culture with species identification using nucleic acid hybridization probes, PCR, or MALDI-TOF.
• Biopsy:
  • Tissue biopsy (skin/lung/lymph node) demonstrates necrotizing or non-necrotizing granulomatous inflammation with positive AFB (Ziehl-Neelsen) stain.

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Differential Diagnostics

• Mycobacterium tuberculosis: Diff by positive IGRA/PPD, person-to-person transmission (requires airborne precautions), and 1 single positive culture is diagnostic.
• Aspergillus / Systemic Mycoses (Histoplasma, Coccidioides): Diff by positive fungal serology/antigen tests and GMS stain (hyphae/yeast) instead of AFB.
• Sarcoidosis: Diff by non-caseating granulomas, ↑ ACE levels, bilateral hilar lymphadenopathy, negative AFB cultures.
• Sporothrix schenckii: Diff by history of rose gardening/pricking, dimorphic fungus on fungal culture vs slow-growing AFB (M. marinum).

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Management

• Pulmonary MAC:
  • First-line: Triple therapy w/ Macrolide (Azithromycin or Clarithromycin) + Rifampin + Ethambutol.
  • Duration: Treat for at least 12 months after negative culture conversion.
• Pulmonary M. kansasii:
  • First-line: Isoniazid + Rifampin + Ethambutol.
• Disseminated MAC Treatment (HIV):
  • First-line: Clarithromycin/Azithromycin + Ethambutol ± Rifabutin. c
  • Initiate ART 2 weeks after starting NTM treatment to reduce IRIS risk.
• Disseminated MAC Prophylaxis (HIV):
  • Primary prophylaxis (Azithromycin weekly) NO longer routinely indicated if ART is initiated immediately; reserved ONLY for CD4 < 50 NOT on effective ART.
• Skin/Soft Tissue (M. marinum):
  • First-line: Clarithromycin + Ethambutol (or Doxycycline) for 2–3 months.
• Pediatric Lymphadenitis:
  • First-line: Complete surgical excision of the affected lymph node (incision & drainage contraindicated due to sinus tract formation).

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Complications

• Immune Reconstitution Inflammatory Syndrome (IRIS): Severe localized/systemic inflammation occurring when ART is started in advanced HIV w/ untreated MAC.
• Progressive Respiratory Failure: End-stage bronchiectasis and pulmonary destruction.
• Drug Toxicities:
  • Ethambutol: Optic neuritis (decreased visual acuity, red-green color blindness; monitor baseline/monthly vision).
  • Macrolides: QT prolongation, ototoxicity, GI intolerance.
  • Rifampin / Rifabutin: Orange discoloration of body fluids, strong CYP3A4 induction (drug interactions).