Multi-drug-resistant tuberculosis natural history, complications and prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
Overview
Tuberculosis has been classified as primary and post primary infection. It can have pulmonary and extra pulmonary manifestations as well as severe parenchymal, vascular, pleural and chest wall complications. The post primary infection can be due to a recent infection or reactivation of an old infection. Further multi drug resistant strains can develop through acquired resistance through inadequate treatment / treatment failure as well as slow gradual genetic mutation resulting in primary resistance. These are transmitted to healthy people resulting in emerging multi drug resistant strains. They can be rifampicin resistant, multi drug resistant, extensively drug resistant and totally drug resistant. The more the number of drugs the strain is resistant to , the poorer is the prognosis.
Natural History
Tuberculosis has been classified as primary or secondary (post primary) infection. It can have pulmonary and extra pulmonary manifestations as well as severe parenchymal, vascular, pleural and chest wall complications. Pulmonary complications include pleural effusions, cavitations, lymphadenopathy, airway obstruction, pneumonia and bronchiectasis. The hematogenous dissemination of infection can lead to miliary tuberculosis. The post primary infection can be due to a recent infection or reactivation of an old infection. Without treatment, 1/3 of patients with active tuberculosis dies within 1 year of the diagnosis, and more than 50% during the first 5 years. But with early diagnosis and treatment it has a good prognosis.
- Drug resistant strains of Mycobacterium tuberculosis can develop due to failure of the full course of treatment for primary tuberculosis or indirect treatment of direct or indirect monotherapy. This mechanism is called as acquired resistance.
- Mycobacterium tuberculosis also has the ability to undergo slow , constant mutation resulting in resistant mutant organism. This process is known as primary resistance. The natural phenomenon of this mutation varies from drug to drug as follows.
- Isoniazid : One in every 106 cell division
- Pyrazinamide : One in every 105 cell division
- Streptomycin : One in every 106 cell division
- Ethambutol : One in every 105 cell division
- Rifampicin : One in every 109 cell division
The anti tubercular drugs kills the susceptible bacteria , resulting in the selection of resistant mutants in the bacterial population and the emergence of multi drug resistant tuberculosis. The figure depicts the emergence of multi drug resistance strains by both the mechanisms. Due to inadequate treatment and failure of monotherapy , acquired drug resistance can occur in patients infected with Mycobacterium tuberculosis. Such strains can pass the drug resistance to the following generation as well as spread the multi drug resistant organism to other people. Also slow gradual genetic mutation can occur in the strains resulting in the primary resistance development and emergence of multi drug resistant strains.[1]
Complications
Extensively drug resistant tuberculosis
- A rare type of MDR TB, Extensively drug resistant TB is defined as TB which is resistant to isoniazid and rifampin, plus resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).
- Because XDR TB is resistant to the most powerful first-line and second-line drugs, patients are left with treatment options that are much less effective.
- XDR TB is of special concern for persons with HIV infection or other conditions that can weaken the immune system. These persons are more likely to develop TB disease once they are infected, and also have a higher risk of death once they develop TB.
Prognosis
- MDR-TB is more difficult to treat than drug susceptible strains of Tuberculosis and one third of the people affected with MDR-TB die. The prognosis is worse for XDR than MDR.
- The second line of drugs used in MDR has more side effects and are usually less effective.
References
- ↑ "Multi drug resistant TB" (PDF).