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 Manifestations
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
- Cutaneous tuberculosis
Latent tuberculosis
- Refers to chronic latent infection contained within granulomas that may reactivate in the future
- Refer to Latent tuberculosis infection
Other
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
Special Populations
Liver Disease
- Most of the first-line medications (except ethambutol) can cause drug-induced hepatotoxicity and should be avoided
- Rifampin may be considered in more extensive disease
- In general, a combination of fluoroquinolone plus ethambutol plus an injectable such as amikacin for the first 2 months, followed by fluoroquinolone and ethambutol alone to complete 18 months total
Prevention
Vaccination
- BCG vaccine given at or shortly after birth in many countries
Infection Prevention and Control
- All cases of suspected tuberculosis should be placed in airborne isolation until three sputum smears are negative for tuberculosis, unless it is still suspected and no other diagnosis is made
- Sputum samples minimum of 1 hour apart, and at least one early morning sample
- Three induced sputa are preferable to one bronchoscopy
- Can accept a single negative PCR test if patient is low probability
- Can accept two negative PCR tests or 1 negative PCR and 2 negative smears if patient is high probability
- For patients with smear-negative, culture-positive, drug-susceptible respiratory TB:
- Continue airborne precautions until clinical evidence of improvement and a minimum of 2 weeks of effective therapy
- Can be discharged home provided there is clinical improvement, drug-resistant TB is not suspected, and there is no contraindication for home isolation
- For patient with smear-positive, culture-positive, drug-susceptible respiratory TB:
- Continue airborne precautions as above, but additionally require three negative sputum smears to be negative before they are taken out of airborne isolation
- Can be discharge home as above
- For patients with rifampin- or multidrug-resistant TB:
- Continue airborne precautions as above, but additionally require three negative sputum cultures to be negative before they are taken out of airborne isolation
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.
- ^ Jussi J. Saukkonen, David L. Cohn, Robert M. Jasmer, Steven Schenker, John A. Jereb, Charles M. Nolan, Charles A. Peloquin, Fred M. Gordin, David Nunes, Dorothy B. Strader, John Bernardo, Raman Venkataramanan, Timothy R. Sterling. An Official ATS Statement: Hepatotoxicity of Antituberculosis Therapy. American Journal of Respiratory and Critical Care Medicine. 2006;174(8):935-952. doi:10.1164/rccm.200510-1666st.
