Mycobacterium Tuberculosis (MTB) and Non-tubercular mycobacterium (NTM)

Ally Glover

Mycobacterium tuberculosis (MTB)

  • Micro profile: small, aerobic, acid-fast bacillus
  • Epidemiology overview: 8,331 reported TB cases in US in 2022 per CDC. Up to 13 million people living in the US with latent TB.
  • Terminology: some discrepancies / evolution of language around TB
    • Active tuberculosis (now often called Tuberculosis Disease)
    • Latent TB Infection (now often called Tuberculosis Infection)
  • Transmission: inhalation of aerosolized droplets from an infected individual
  • Possible outcomes of this exposure/transmission:
    • Immediate clearance by host defenses
    • Primary TB Disease
    • TB infection (Latent Disease)

Presentations 

  • TB Disease (Active TB)
    • Primary TB (after first exposure)
      • Fever, cough, pleuritic chest pain
      • CXR: hilar/mediastinal LAD, pulmonary consolidation, pleural effusion. Some patients can present with isolated pulmonary cavitations.
    • Reactivation (post primary TB, years after exposure often)
      • Presents more insidiously: fever, cough, malaise, weight loss, dyspnea. There is an overlap with primary TB.
      • CXR: usually involves apical and posterior upper lobe consolidations, often with cavitations
    • Extrapulmonary manifestations: lymphadenitis, pericarditis (can cause tamponade), genitourinary (can cause infertility even in women), peritoneal involvement, and CNS involvement
      • Disseminated TB
      • Also referred to as miliary TB. Can range from acute to chronic in presentation.
      • Dissemination is more often seen in immunocompromised hosts (including patients with HIV/AIDS).
    • TB Infection (Latent Disease)
      • Asymptomatic by definition
      • The immune system has contained any active disease such that individuals are not infectious
      • CXR may show old, healed tuberculosis but patient has no history of treatment. This patient would be very high risk for reactivation.

Testing & Diagnosis

  • Who to test?
    • Clinical judgement is key
    • In general, think about patients about to go on TNF-alpha blocker or a similar biologic, patients with malignancies, patients with newly diagnosed or undiagnosed HIV, patients at high risk due to living conditions (unhoused individuals in shelters, incarcerated patients).
  • Tuberculin skin test (TST) and interferon gamma release assay (IGRA) are often used for screening purposes
    • If someone had the BCG vaccine, cannot use TST
  • If you are concerned for symptomatic TB disease, need to get 2 AFB sputum samples with Xpert testing before can come off TB precautions
    • Xpert MTB/RIF detects the MTB rproB gene. Also detects rifampin resistance.
      • 98% sensitive for a single sputum specimen in smearpositive culture-positive cases; approximately 70% sensitive for smear negative culture-positive cases (this increases to 90% if you test 3 samples).

Treatment

  • TB Infection (Latent TB):
    • Different options:
      • Rifampin (RIF) daily for 4 months (4R)
      • Isoniazid (INH) and RIF daily for 3 months (3HR)
      • INH and rifapentine (RPT) weekly for 3 months (3HP)
      • INH for 6-9 months (alternative if contraindication to rifamycins)
  • TB Disease:
    • Multi drug regimen for at least 6 months for pulmonary TB
      • INH, RIF, pyrazinamide (PZA), and ethambutol (EMB) for 2 months followed by INH and RIF for 4 more months
    • For CNS involvement: 12 months of therapy plus steroids
    • For bone and joint involvement: 6-9 months of therapy
    • For certain patients with drug-susceptible TB confined to pulmonary system: new recommendation that can do a 4-month course where rifapentine (RPT) and moxifloxacin (MOX)
      • 2 months of RPT, INH, PZA, and MOX, followed by 9- weeks of RPT, INH, and MOX
      • If patient has HIV, remember that TB meningitis is one of the infections most likely to result in IRIS, so ART initiation is held in this case
      • These treatment summaries are for non-pregnant patients

Non tubercular mycobacterium (NTM)

  • These are mycobacteria species that do not cause tuberculosis or leprosy
  • Ubiquitous in the environment
  • Most well-known species: mycobacterium avium complex (MAC)

NTM manifestations in patients

  • Pulmonary disease
    • Pulmonary MAC
      • Presents usually with cough, weight loss, fatigue
      • Often occurs in patients with underlying lung disease (bronchiectasis, COPD) or patients with prior TB
      • Another common phenotype: women > 50 who are nonsmokers
      • More likely to have CFTR mutations
      • Common imaging findings: nodules, bronchiectasis, and/or cavities
      • Diagnosis: symptoms, imaging findings, 2 positive sputum samples with NTM growth or 1+ bronchial washing (if patient symptomatic)
    • Disseminated infections
      • Most often seen with HIV/AIDS
      • Disseminated MAC presents usually with fever, night sweats, weight loss
  • End organ involvement: bone marrow (manifesting as cell line derangements), adenopathy/hepatosplenomegaly, GI (manifesting as diarrhea, abdominal pain), and pulmonary
  • Diagnosis: AFB blood cultures, culture & staining/path from end organ areas of involvement (i.e. bone marrow biopsy)
  • NTM infections can also present as superficial lymphadenitis or skin infections

Treatment 

  • Depends on macrolide susceptibility
  • For pulmonary MAC: 3 drug regimen consisting of a macrolide (usually azithromycin), a rifamycin (usually rifampin), and ethambutol.
    • Aminoglycoside also sometimes used depending on type of pulmonary disease
  • Duration of treatment is usually 15-18 months. Depends on how quickly patients can clear their cultures as you need treatment until 2 consecutive sputum cultures are negative for at least 12 months
  • Disseminated disease treatment is more complicated and is affected by ART often in patients with HIV, so reach out to ID
    • ART should be started in individuals with new HIV diagnosis as soon as MAC treatment is started (unless another co-infection prevents this due to risk of IRIS)
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