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
- 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
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.
- ^ 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.
