Mycobacterium Tuberculosis (MTB) and Non-Tubercular Mycobacterium

Michael Kaminski

Mycobacterium Tuberculosis (MTB)

  • Tuberculosis Infection (latent TB) vs Tuberculosis Disease (Active TB) 
  • Transmitted via inhalation of aerosolized droplets containing small, aerobic, acid-fast bacilli 
  • Possible outcomes: immediately clear vs primary disease; both may progress to latent disease 
  • TB Infection (Latent TB): 
  • Asymptomatic. The immune system contained active disease, not infectious. No Hx of treatment. CXR: old, healed TB. 
  • Who to Screen: Exposed/Close contacts of TB pts, High-risk for reactivation (HIV, hematologic malignancies, TNFa inhibitors, transplant, compatible CXR), Moderate-risk: DM, chronic steroids, High-incidence country immigrants, congregate settings (Homeless shelters, prison), healthcare workers 
  • How to Screen: IGFA preferred, alternative TST (not for BCG vaccinated); if positive: CXR ± sputum to exclude active TB 
  • TB Infection (Latent TB) Treatment Regimens: 
    • 4R: Rifampin daily×4M 
    • 3HP: INH + rifapentine weekly×3M (DOT preferred) 
    • 3HR: INH + Rifampin daily×3M o 9H: INH × 9M if rifamycin contraindicated 
    • Note: Monitor LFTS, stop if symptomatic with AST >3×ULN or asymptomatic >5×ULN; Rifamycins: DDIs (warfarin, OCPs, antiretrovirals); add pyridoxine with INH if neuropathy risk (DM, uremia, EtOH)

TB Disease (Active TB) 

  • Primary TB (on first exposure): Fever, cough, pleuritic chest pain. CXR: hilar/mediastinal LAD, pulmonary consolidation, pleural effusion. 
  • Reactivation (post primary TB, years after exposure often): Insidious fever, cough, malaise, weight loss, dyspnea. CXR: apical and posterior upper lobe consolidations, +/- cavitations 
  • Disseminated TB (miliary TB), more often in immunocompromised hosts (AIDS, transplant) 
  • Extrapulm manifestations: lymphadenitis, pericarditis, GU (can cause infertility even in women), peritoneal involvement, and CNS (meningitis, abscesses) 
  • Who to Test: cough >2–3W, fevers, night sweats, or weight loss + risk factors: prior TB infection/disease, exposure, or residence/travel to endemic regions, incarcerated, IVDU, family Hx of TB; immunocompromised (HIV, transplant); Drug-resistant TB should be suspected with prior TB treatment, therapy failure, or exposure to known drug-resistant cases. 
  • How to Test: CXR, 3x sputums (≥8h apart, one early morning) for AFB smear, mycobacterial Cx, and NAAT Xpert MTB/RIF (detects rifampin resistance, indicative of MDR TB). +/- TST or IGRA. In HIV patients with CD4 <200, consider urine LAM if available. 
  • Report all confirmed/suspected cases to public health within 24 hours. Link with instructions: https://www.tn.gov/health/rpd/tuberculosis-infection.html 
  • TB Disease (Active TB) Treatment Regimens: 
    • Traditional (≥6 months, preferred): Intensive phase (2M INH + RIF + PZA + EMB) followed by Continuation phase (≥4M INH + RIF) 
    • 4-Month Regimen (alternative for eligible patients): Intensive (8W): rifapentine + INH + PZA + moxifloxacin followed by Continuation (9W): rifapentine + INH + moxifloxacin 
    • 4-Month Regimen CI: pregnancy, cardiac history (QTc risk), renal failure, extrapulmonary TB 
  • Usually treated by local DOH with DOT, monitored with sputum AFB Cxs, LFTs (hold if bili >3, AST/ALT >5x ULN) 
  • For CNS involvement: Tx 12M plus steroids 
  • If HIV+, TB meningitis is one of the infections high risk for IRIS, ART initiation is delayed 
  • For bone and joint involvement: Tx 6-9M - For MDR-TB, TB in HIV pts, pregnant patients, consult ID

Nontuberculous Mycobacterium (NTM)

Pathogenesis 

  • 190 NTM species; most common: M. avium complex (MAC) and M. abscessus. Environmental organisms (soil, water, plumbing); route = inhalation of aerosolized particles. Classified as slowly growing (SGM, e.g., MAC, >7 days) vs. rapidly growing (RGM, e.g., M. abscessus, <7 days) 
  • Thick lipid-rich cell wall → acid-fast staining, antimicrobial resistance, biofilm formation 
  • Inhalation of aerosolized particles that reach alveoli > chronic granulomatous inflammation > bronchiectasis, bronchiolitis, nodules, cavitation 
  • Risk factors for infection: bronchiectasis, CF, COPD, immunosuppression (TNFa antagonists, corticosteroids), low BMI, aging

Clinical Presentation 

  • Respiratory: Chronic cough (+/- sputum), dyspnea, hemoptysis 
  • Constitutional symptoms: Fevers, nights sweats, fatigue, anorexia, weight loss 
  • Disseminated and extrapulmonary involvement (more commonly seen with HIV/AIDS) 
    • Bone marrow infiltration (cytopenias), LAD/HSM, GI (diarrhea, abdominal pain), cellulitis/skin ulcers

Workup 

  • Diagnosis requires: compatible clinical + radiologic + microbiologic criteria 
    • Radiographic Criteria: High-resolution chest CT with tree in bud, nodules, bronchiectasis, +/- consolidation or pleural effusion (classified into nodular bronchiectatic or fibrocavitary) 
    • Microbiologic Criteria: ≥2 consecutively positive sputum Cxs OR ≥1 positive BAL Cx OR ≥1 positive Cx from bronch Bx biopsy or other sterile site; need repeated detection of SAME species 
    • Dx of Extrapulmonary Disease: AFB BCxs, Cx+staining/path involved end organs (i.e. BMBx) 
  • Species-level ID via MALDI-TOF, PCRs 
  • Antimicrobial susceptibility testing required for macrolides, aminoglycosides, rifampin

Treatment 

  • Supportive Care: Treat comorbidities, optimize nutrition, airway clearance therapy 
  • Consult ID regarding abx and post-hospitalization follow up, in general: 
    • Macrolide (if susceptible) — backbone of therapy 
    • Add ethambutol for slow growing myco (prevents acquired macrolide resistance) 
    • Add rifamycin (for SGM) or additional agents per susceptibility testing (RGM) 
    • IV aminoglycoside or inhaled liposomal amikacin for severe/treatment-limited disease 
    • Surgery for focal, severe, or treatment-refractory disease 
    • Duration is long, ~12+M post sputum Cx conversion, usually duration 15-18M
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