Multidrug-Resistant Tuberculosis

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

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Basics

Description

  • Multidrug-resistant tuberculosis (MDR-TB) is disease that is resistant to first-line medications: isoniazid, pyrazinamide, streptomycin, ethambutol, and rifampin.
  • Extensively, drug-resistant tuberculosis (XDR-TB) is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least 1 of 3 second-line medications (amikacin, capreomycin, kanamycin).

Epidemiology

Incidence
  • TB affected 10 million worldwide in 2017.
  • TB in the United States (2017): 9,105 (2.8/100,000; 123 MDR)

Prevalence
Asians are most commonly affected, followed by Hispanics and non-Hispanics. African Americans have the highest disease rates.

Etiology and Pathophysiology

  • Mycobacterium tuberculosis is an obligate aerobe that is slow growing. It is nonspore forming, nonmotile, and facultatively anaerobic.
  • 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
    • 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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