Management and Treatment
Management and Treatment
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Clinical Genomics: Practical Applications in Adult Patient Care
82: Tuberculosis
Management and Treatment
Management
Therapeutics
For adults with pulmonary TB, the most frequently used treatment is a combination of the firstline antiTB drugs isoniazid, rifampicin, ethambutol,
and pyrazinamide for 2 months, followed by isoniazid, rifampicin for 4 months. For adults with TB meningitis isoniazid, rifampin, ethambutol, and
streptomycin may be used, for 12 months. All drugs are to be administered in a directly observed treatment program (DOTS) to increase compliance
and reduce development of secondary antibiotic resistance. An increasing number of Mtb strains are resistant to firstline antibiotics and need to be
treated with secondline (MDRTB) or thirdline (XDRTB) regimens, which tend to have limited efficacy and more serious side effects. Ideally, empirical
regimens are adjusted according to drugsusceptibility of Mtb strains, but culture and susceptibility testing are not widely available in many endemic
regions.
Prevention
Infants or young children in high TB prevalence areas are routinely vaccinated with the attenuated M. bovis BCG vaccine. Although BCG is effective
against meningeal TB and miliary TB in children, it has shown limited and inconsistent efficacy against pulmonary TB, which is the most frequent
manifestation and only contagious form of the disease. BCG efficacy varies widely in human populations, and is least effective in areas with a high rate
of infection with NTM. NTM may cause an immune response comparable to BCG, thereby masking or blocking the effect of the vaccine.
Isoniazid treatment of TSTpositive and/or IGRApositive TBexposed individuals for 6 to 9 months affords 70 to 80 protective efficacy against
developing active TB, but may have side effects. This approach is therefore generally limited to persons in whom the infection is acquired recently. In
individuals that need antiTNF treatment (rheumatoid arthritis, Crohn disease), or that are in need of immunosuppression for other reasons, latent TB
infection has a very high risk of reactivation often with a severe course and should be screened for and, if present, treated before starting such therapy.
Pharmacogenetics
Pharmacogenetics is not yet incorporated widely in the treatment of patients with TB, although some limited pharmacogenetic information is available
(Table 822).
Isoniazid can be inactivated by two different pathways: the first pathway involves Nacetyltransferase 2 (NAT2)mediated acetylation, resulting in
acetylisoniazid which is hydrolyzed to acetylhydrazine. Acetylhydrazine is oxidized by cytochrome P450 2E1 (CYP2E1) to form hydroxylamines, which
are intermediates in the formation of established hepatotoxic metabolites. Some of these hepatotoxic metabolites can be detoxified by glutathioneS
transferase (GST). The second pathway involves direct hydrolysis of isoniazid to hydrazine, a potent hepatotoxin.
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