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 (i.e. PCR testing) before can come off TB precautions
  - TST and IGRA should not be used as reliable tests for TB disease
  - Xpert MTB/RIF detects the MTB rproB gene. Also detects rifampin resistance.
    - 98% sensitive for a single sputum specimen in smear-positive 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)