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, aerobic acid-fast bacillus
• Cell wall has high lipid content
• Generation time is very long (15 to 20 hours)
• M. tuberculosis is a complex that comprises seven species:
  • M. tuberculosis sensu stricto: most common causative organism worldwide
  • M. africanum: 50% of cases in West africa
  • M. canetti: rare cause in Eastern African
  • M. bovis: disease in cattle but can infect humans
  • M. caprae: disease in cattle
  • M. microti: disease in rodents
  • M. pinnipdeii: disease in seals, with rare human infection

Epidemiology

• Typically spread via airborne route
  • Droplets are expelled during coughing, sneezing, or talking, and are suspended in the air
  • They can remain for up to 30 minutes
  • Killed by ultraviolet light
  • Not transmitted via fomites
• About a third of the world is infected, mostly as latent tuberculosis
  • This progresses to active tuberculosis at about 3 or 4% in the first year and 5% over the rest of their life
• Reinfection accounts for ~40% of active tuberculosis in endemic countries
• Highest rates in sub-Saharan Africa and south/southeast Asia

Risk Factors

• Source factors, such as sputum smear positivity, cough, cavitations
• Exposure duration, closeness of contact
• Factors in the exposed person, such as immune compromise, HIV status

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

• Most common presentation of active tuberculosis
• Refer to separate article on pulmonary tuberculosis

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

• See also management of pulmonary tuberculosis
• First-line medications include:
  • Isoniazid 5 mg/kg daily, max 300 mg daily, with pyridoxine 25 mg po daily
  • Rifampin 10 mg/kg dialy
  • Pyrazinamide 25 mg/kg daily, max 2 g daily
  • Ethambutol 20 mg/kg daily, max 1.2 g daily
• Second-line medications include:
  • Streptomycin 15 mg/kg daily, max 1 g
  • Amikacin, kanamycin, or capreomycin 15 mg/kg daily, man 1 g
  • Ethionamide 250 mg BID to TID, max 1 g
  • Para-amino salicylic acid 4 g BID or TID, max 10 g
  • Cycloserine 250 mg BID to TID, max 1 g
  • Levofloxacin 500 to 1000 mg po daily
  • Moxifloxacin 400 to 600 mg daily
  • Rifabutin 300 mg tdaily
  • Clofazimine 100 to 300 mg daily
  • Linezolid 600 mg po daily
• Add steroids for patients with tuberculous meningitis or tuberculous pericarditis
  • e.g. prednisone 40 to 80 mg po daily for 6 to 12 weeks

Drug-induced liver injury (DILI)

• Most common complication leading to treatment interruption, with a mortality of 6-12% if drugs are not stopped
• Pyrazinamide, followed by isoniazid, then rifampin, are the most common causes of liver injury12
• 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

• Canadian Canadian Tuberculosis Standards, 7th Edition (2014)