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Multidrug-Resistant Tuberculosis

Multidrug-Resistant Tuberculosis is a topic covered in the 5-Minute Clinical Consult.

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  • Multidrug-resistant tuberculosis (MDR-TB) is defined as TB disease that is resistant to isoniazid and rifampin.
  • Extensively, drug-resistant tuberculosis (XDR-TB) is defined as resistance to isoniazid and rifampin, plus any fluoroquinolone and at least one of three second-line injectable medications (amikacin, capreomycin, kanamycin).


  • TB affected 9.6 million worldwide in 2014.
  • TB in the United States (2014): 9,421 (2.96/100,000; 91 MDR, and 80 of those were foreign-born)
  • The percentage of MDR-TB cases is ~1.5%.

  • Asians are most commonly affected, followed by Hispanics and non-Hispanics. African Americans have the highest disease rates.
  • The absolute number of cases and the number of deaths per year has decreased.

Etiology and Pathophysiology

  • Mycobacterium tuberculosis is an obligate aerobe that is slow-growing. It is nonspore forming, nonmotile, and facultative.
  • A cell-mediated response by activated T lymphocytes and macrophages forms a granuloma that limits bacillary replication. Destruction of the macrophages produces early “solid necrosis.” In 2 to 3 weeks, “caseous necrosis” develops and latent tuberculosis infection (LTBI) ensues. In immunocompetent persons, the granuloma undergoes “fibrosis” and calcification. In immunocompromised patients, primary progressive TB develops.
  • Drug resistance occurs via various mechanisms:
    • Isoniazid resistance: mutations to katG or inhA responsible for 85–90% of resistance reported by the CDC
    • Rifampin resistance: mutations in the rpoB gene, responsible for encoding the β chain of mycobacterial RNA polymerase
    • Pyrazinamide resistance due to mutations in the pncA gene. The pncA gene is responsible for the enzyme pyrazinamidase that converts pyrazinamide into its active form, pyrazinoic acid.

Risk Factors

  • Previous episode of TB
  • Incomplete adherence to treatment protocol
  • Previous treatment failure and/or relapse
  • Cultures that do not convert to negative during the first 3 months of therapy
  • Exposure to an individual with confirmed (or suspected) MDR-TB
  • Residence, travel, or work in region/institution with high prevalence of known MDR-TB

General Prevention

  • Prompt isolation of infectious patients
  • Directly observed therapy (DOT) for patients with compliance difficulties

Commonly Associated Conditions

HIV coinfection, immunosuppression

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Stephens, Mark B., et al., editors. "Multidrug-Resistant Tuberculosis." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816955/all/Multidrug_Resistant_Tuberculosis.
Multidrug-Resistant Tuberculosis. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816955/all/Multidrug_Resistant_Tuberculosis. Accessed March 26, 2019.
Multidrug-Resistant Tuberculosis. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816955/all/Multidrug_Resistant_Tuberculosis
Multidrug-Resistant Tuberculosis [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 March 26]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816955/all/Multidrug_Resistant_Tuberculosis.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Multidrug-Resistant Tuberculosis ID - 816955 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816955/all/Multidrug_Resistant_Tuberculosis PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -