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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.
- 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
- Prompt isolation of infectious patients
- Directly observed therapy (DOT) for patients with compliance difficulties
Commonly Associated Conditions
HIV coinfection, immunosuppression