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]

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.

Further information: Tuberculosis natural history, complications and prognosis

Author:Alejandro Lemor, MD

• 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.