Mycobacterium tuberculosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Synonyms and keywords: M. Tuberculosis
Overview
Mycobacterium tuberculosis is the bacterium responsible for tuberculosis. It is an aerobic, non-encapsulated, non-motile, acid-fast bacillus. M. tuberculosis belongs to the Mycobacterium tuberculosis complex, that also includes bacteria, such as M. bovis and M. africanum. The bacterium has a very slow rate of replication, and its genetic variations account for the different strains and the growing drug resistance. M. tuberculosis has tropism for different kinds of human cells, with preference for cells of the lung. It may infect different species, yet human beings are its frequent natural reservoir.
Taxonomy
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Cellular organisms; Bacteria; Actinobacteria; Actinobacteria; Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex; M. tuberculosis[3]
Biology
Mycobacterium tuberculosis belongs to the Mycobacterium tuberculosis complex. This complex includes M. tuberculosis, M. bovis, M. africanum, M. canetti, and M. microti.[4]
M. tuberculosis is an obligate aerobe, non-encapsulated, non-motile, acid-fast bacillus. Slender, straight or slightly curved bacillus with rounded ends, occuring singly, in pairs or in small clumps. It does not form spores and its ideal growing environment includes tissues with high levels of oxygen. It cannot be considered gram-positive or gram-negative due to the high lipid content of the cell wall, which is impermeable to the dyes used until combined with an alcohol. On microscopic examination of sputum samples, the bacteria cannot be distinguished from other acid-fast bacteria, such as Nocardia spp.[4] M. tuberculosis has a very slow rate of replication, taking about 15 to 20 hours to divide. This characteristic, added to its ability to remain in the latent state for long periods of time, account for the long treatment duration required.[4]
Genetic variances in the M. tuberculosis genome lead to important phenotypical changes. There are many different strains of the bacteria, 6 of which have specific geographical distribution. Three strains, the Beijing family, strain W and the W-like strains, were noted to be associated with resistance to treatment drugs.[5][6]
Tropism
M. tuberculosis does not have specific tissue tropism and is capable of infecting almost all human tissues. However, M. tuberculosis strives most in tissues with high oxygen levels, hence the high rate of pulmonary tuberculosis. [4]
Natural Reservoir
Human beings are the main natural reservoir for M. tuberculosis, however, the bacteria may infect other species.[4]
Treatment
Antimicrobial regimen
- Standard Regimens for New Patients [7]
- Adult
- Initial phase
- Preferred regimen: Isoniazid 300 mg PO (5 mg/kg/day) AND Rifampicin 600 mg PO (10 mg/kg/day) AND Pyrazinamide 2 g PO (25 mg/kg/day) AND Ethambutol 1.6 g PO (15 mg/kg/day), each drug daily for 8 weeks
- Alternative regimen (1): Isoniazid 300 mg/day PO for 2 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO for 2 weeks (10 mg/kg/day) AND Pyrazinamide 2 g/day PO for 2 weeks (25 mg/kg/day) AND Ethambutol 1.6 g PO for 2 weeks (15 mg/kg/day), followed by Isoniazid 300 mg/day PO twice weekly for 6 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO twice weekly for 6 weeks (10 mg/kg/day) AND Pyrazinamide 2 g/day PO twice weekly for 6 weeks AND Ethambutol 1.6 g PO for 2 weeks (15 mg/kg/day)
- Alternative regimen (2): Isoniazid 300 mg/day PO thrice weekly for 8 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day P.O thrice weekly for 8 weeks (10 mg/kg/day) AND Pyrazinamide 2g/day PO thrice weekly for 8 week (25 mg/kg/day) AND Ethambutol 1.6 g PO thrice weekly for 8 weeks (15 mg/kg/day)
- Continuation phase
- Preferred regimen (1): Isoniazid 300 mg daily PO (5 mg/kg/day) AND Rifampicin 600 mg daily PO (10 mg/kg/day) for 18 weeks
- Preferred regimen (2): Isoniazid 300 mg PO twice weekly (5 mg/kg/day) AND Rifampicin 600 mg/day PO twice weekly (10 mg/kg/day) for 18 weeks
- Alternative regimen (1): Isoniazid 300 mg/day PO biweekly for 18 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO biweekly for 18 weeks (10 mg/kg/day)
- Alternative regimen (2): Isoniazid 300 mg/day PO thrice weekly for 18 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO thrice weekly for 18 weeks (10 mg/kg/day)
- Pediatric
- Initial phase
- Preferred regimen: Isoniazid 10 mg/kg PO (Max: 300 mg/day) AND Rifampicin 15 mg/kg PO (Max: 600 mg/day) AND Pyrazinamide 35 mg/kg PO (Max: 2 g/day) AND Ethambutol 20 mg/kg PO (Max: 1.6 g/day), each for 8 weeks
- Continuation phase
- Preferred regimen: Isoniazid 10 mg/kg PO (Max: 300 mg/day) AND Rifampicin 15 mg/kg PO (Max: 600 mg/day), each drug daily for 18 weeks
- MDR Tuberculosis [8]
- Adult
- Preferred regimen: Pyrazinamide 20–30 mg/kg OR Ethambutol 15–25 mg/kg OR Rifabutin 5 mg/kg AND Capreomycin 15 mg/kg OR Kanamycin 15 mg/kg OR Amikacin 7.5-10 mg/kg OR Streptomycin 12–18 mg/kg AND Levofloxacin 500-1000 mg OR Moxifloxacin 400 mg OR Ofloxacin 400 mg AND Ethionamide 15-20 mg/kg OR Protionamide 15-20 mg/kg OR Cycloserine 10-15 mg/kg OR Terizidone 10-20 mg/kg OR Para-aminosalicylic acid 8-12 g/d divided q8-12h
- Pediatric
- Preferred regimen: Pyrazinamide 20-30 mg/kg (Max: 600 mg) OR Ethambutol 15-20 mg/kg OR Rifabutin 5 mg/kg AND Capreomycin 15-30 mg/kg (Max: 1000 mg) OR Kanamycin 15-30 mg/kg (Max: 1000 mg) OR Amikacin 15-22.5 mg/kg (Max: 1000 mg) OR Streptomycin 12-18 mg/kg AND Levofloxacin 7.5-10 mg/kg OR Moxifloxacin 7.5-10 mg/kg OR Ofloxacin 15-20 mg/kg divided q12h (Max:800 mg) AND Ethionamide 15-20 mg/kg divided q12h (Max: 1000 mg) OR Protionamide 15-20 mg/kg divided q12h (Max: 1000 mg) OR Cycloserine 10-20 mg/kg (Max: 1000 mg) OR Terizidone 10-20 mg/kg (Max: 1000 mg) OR Para-aminosalicylic acid 150 mg/kg divided q8-12h(Max: 12 000 mg)
- XDR Tuberculosis
- Adult
- Preferred regimen: Pyrazinamide 20–30 mg/kg OR Ethambutol 15–25 mg/kg OR Rifabutin 5 mg/kg AND Ethionamide 15-20 mg/kg OR Protionamide 15-20 mg/kg OR Cycloserine 10-15 mg/kg OR Terizidone 10-20 kg/mg OR Para-aminosalicylic acid 8-12 g/d divided q8-12h AND Clofazimine 50 mg/d AND 300 mg once a month OR Amoxicillin/clavulanate 500 mg/125 mg q12h OR Linezolid 300-600 mg OR Imipenem 500mg q6h OR Clarithromycin 500-1000 mg q12h OR Thioacetazone 2.5 mg/kg OR Isoniazid (high-dose) 16–20 mg/kg
- Pediatric
- Preferred regimen: Pyrazinamide 20-30 mg/kg (Max: 600 mg) OR Ethambutol 15 mg/kg OR Rifabutin 5 mg/kg AND Ethionamide 15-20 mg/kg (Max: 1000 mg) OR Protionamide 15-20 mg/kg (Max: 1000 mg) OR Cycloserine 10-20 mg/kg (Max: 1000 mg) OR Terizidone 10-20 mg/kg (Max: 1000 mg) OR Para-aminosalicylic acid 150 mg/kg/d divided q8-12h AND Clofazimine 50 mg/d AND 300 mg once a month OR Amoxicillin/clavulanate OR Linezolid 300-600 mg OR Imipenem 500mg q6h OR Clarithromycin 500-1000 mg q12h OR Thioacetazone 2.5 mg/kg OR Isoniazid (high-dose) 16–20 mg/kg
References
- ↑ "http://phil.cdc.gov/phil/details.asp". External link in
|title=(help) - ↑ "http://phil.cdc.gov/phil/details.asp". External link in
|title=(help) - ↑ "Mycobacterium tuberculosis".
- ↑ 4.0 4.1 4.2 4.3 4.4 Lawn SD, Zumla AI (2011). "Tuberculosis". Lancet. 378 (9785): 57–72. doi:10.1016/S0140-6736(10)62173-3. PMID 21420161.
- ↑ Smith NH, Hewinson RG, Kremer K, Brosch R, Gordon SV (2009). "Myths and misconceptions: the origin and evolution of Mycobacterium tuberculosis". Nat Rev Microbiol. 7 (7): 537–44. doi:10.1038/nrmicro2165. PMID 19483712.
- ↑ Gagneux S, Small PM (2007). "Global phylogeography of Mycobacterium tuberculosis and implications for tuberculosis product development". Lancet Infect Dis. 7 (5): 328–37. doi:10.1016/S1473-3099(07)70108-1. PMID 17448936.
- ↑ Treatment of tuberculosis guidelines. Geneva: World Health Organization. 2010. ISBN 9789241547833.
- ↑ "The use of delamanid in the treatment of multidrug-resistant tuberculosis" (PDF).