Mycobacterium tuberculosis

• Mycobacterium tuberculosis causes tuberculosis
• Most commonly pulmonary TB but extrapulmonary tuberculosis is possible (including adenitis, gastrointestinal TB, pericarditis, meningitis)
• Standard treatment for susceptible TB is RIPE x2mo then RI x4mo

Background

Microbiology

• Fastidious acid-fast bacillus

Epidemiology

• Reinfection accounts for ~40% of active tuberculosis in endemic countries
• Latent tuberculosis in ~30% of the global population

Clinical Presentation

Classification

• Primary vs. reactivation vs. reinfection
• Latent vs. active

Primary tuberculosis

• Primary tuberculosis is usually asymptomatic
• Possible presentations include mild URTI with cough and/or fever
• May be seen on CXR as infiltrate in mid-lung zones with hilar adenopathy
• Ghon complex, especially in children
• May progress in children and the immunocompromised patients
• Immunological phenomena
  • Erythema nodosum
  • Phlyctenular conjunctivitis
  • Erythema induratum

Pulmonary tuberculosis

• Subacute or chronic cough (at least 2 to 3 weeks) eventually becoming productive and occasionally involving hemoptysis
  • Should be suspected in any patient with cough and HIV infection
• Constitutional symptoms, with fevers, night sweats, and unexplained weight loss
• Usually from reactivation of latent tuberculosis infection, and usually reactivates in lung apices
• May transiently improve with partially-active antibiotics such as fluoroquinolones

Extra-pulmonary tuberculosis

• Pleural tuberculosis is most common extrapulmonary site
• Scrofula (cervical lymph node infection) next-most common
• Tuberculous meningitis
• Tuberculous pericarditis
• Renal tuberculosis
• Abdominal tuberculosis
• Gastrointestinal tuberculosis

Latent tuberculosis

• Refers to chronic latent infection contained within granulomas that may reactivate in the future
• Refer to Latent tuberculosis infection

Investigations

• Radiography: chest x-ray with or without CT chest
  • Primary TB: consolidation, lymphadenopathy, pleural effusion, Ghon complex
  • Reactivation TB: patchy upper-lobe consolidation, cavitation, fibrosis, pleural disease
  • Miliary TB: uniform 1-3 mm diameter diffuse nodules
• Microbiology:
  • Samples can include routine or induced sputum (x3) or bronchoscopy, or tissue sample
  • Spontaneous sputum should include at least one morning sputum, ideally, but can be done all in a row at least one hour apart if needed
  • Acid-fast bacillus culture of sputum x3 is about 70% sensitive, and PCR (ANTB) x1 is about 75% sensitive

Management

• Standard HREZ x2mo then HR x4mo
  • Isoniazid 5mg/kg/d, max 300mg daily
  • Rifampin 10mg/kg/d
  • Pyrazinamide 25mg/kg/d, max 2g daily
  • Ethambutol 20mg/kg/d, max 1.2g daily
  • Pyridoxine 25 mg po daily
• Airborne precautions until:
  • Treated for at least 2 weeks
  • 3x negative sputum smears
    • Collected at 8- to 24-hour intervals, including one early morning collection
  • Improvement in symptoms

Drug-induced liver injury (DILI)

• Most common complication leading to treatment interruption, with a mortality of 6-12% if drugs are not stopped
• Rifampin is probably the highest offender in combination therapy, though some studies suggest it is highest with pyrazinamide, followed by isoniazid1
• Most patients can have the same TB drugs reintroduced without recurrence of DILI, though recurrence can be delayed
• Procedure
  • Hold if ALT >120 and symptoms, if ALT >200 even without symptoms, or bili >2x ULN
  • Switch to second-line meds
  • Reintroduce the original drugs once AST & ALT are <2x ULN
  • Only rechallenge with pyrazinamide if it was a mild case

Adherence to Treatment

• Refer to Let's Talk TB

Further Reading

• Tuberculosis Standards, 7th Edition (2014)