Mycobacterium tuberculosis
From IDWiki
- 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
Diagnosis
- Latent tuberculosis testing
- Tuberculin skin test (TST)
- Interferon-gamma release assay (IGRA)
- Serology or immunologic testing
- Urine lipoarabinomannan antigen
- 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
- Molecular testing
- PCR, including GeneXpert
Management
Antibiotics
Drug | Dose | Side effects |
---|---|---|
First-line medications | ||
Isoniazid | 5 mg/kg daily, max 300 mg daily, with pyridoxine 25 mg po daily | Rash, hepatitis, neuropathy, CNS toxicity, anemia |
Rifampin | 10 mg/kg daily | Drug interactions, rash, hepatitis, flu-like illness, neutropenia, thrombocytopenia |
Pyrazinamide | 25 mg/kg daily, max 2 g daily | Hepatitis, rash, arthralgia, gout |
Ethambutol | 20 mg/kg daily, max 1.2 g daily | Optic/retrobulbar neuritis, rash |
Second-line medications | ||
Streptomycin | 15 mg/kg daily, max 1 g | Auditory and vestibular toxicity, renal toxocity, avoid in pregnancy |
Amikacin, kanamycin, or capreomycin | 15 mg/kg daily, man 1 g | |
Ethionamide | 250 mg BID to TID, max 1 g | GI disturbance, hepatotoxicity, endocrine effects, neurotoxicity, avoid in pregnancy |
Para-amino salicylic acid | 4 g BID or TID, max 10 g | GI disturbance, hepatic dysfunction, hypothyroidism, avoid in aspirin allergy |
Cycloserine | 250 mg BID to TID, max 1 g | Avoid in epilepsy, psychiatric illness, and alcoholism |
Levofloxacin | 500 to 1000 mg po daily | GI disturbance, headache, anxiety, tremor, long QT, avoid in pregnancy and children |
Moxifloxacin | 400 to 600 mg daily | |
Rifabutin | 300 mg daily | Hepatotoxicity, uveitis, thrombocytopenia, neutropenia, drug interactions |
Clofazimine | 100 to 300 mg daily | Skin discolouration, conjunctiva, cornea, body fluid discolouration, GI intolerance, photosensitivity |
Third-line medications | ||
Linezolid | 600 mg po daily | |
Bedaquiline | 400 mg po daily for 2 weeks followed by 200 mg thrice weekly | Arthralgias, dizziness, headache, hyperuriemia, insomnia, myalgia, nausea, prolonged ECG QT interval, pruritus, and vomiting |
Pretomanid | ||
Delamanid | ||
Adjunctive therapies | ||
Corticosteroids for patients with tuberculous meningitis or tuberculous pericarditis | Prednisone 40 to 80 mg po daily for 6 to 12 weeks |
Immune reconstitution inflammatory syndrome (IRIS)
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
References
- ^ Daphne Yee, Chantal Valiquette, Marthe Pelletier, Isabelle Parisien, Isabelle Rocher, Dick Menzies. Incidence of Serious Side Effects from First-Line Antituberculosis Drugs among Patients Treated for Active Tuberculosis. American Journal of Respiratory and Critical Care Medicine. 2003;167(11):1472-1477. doi:10.1164/rccm.200206-626oc.