Multidrug-Resistant Tuberculosis
Basics
Basics
Basics
Description
Description
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
Epidemiology
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
Etiology and Pathophysiology
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
Risk Factors
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
General Prevention
General Prevention
- Prompt isolation of infectious patients
- Directly observed therapy (DOT) for patients with compliance difficulties
Commonly Associated Conditions
Commonly Associated Conditions
Commonly Associated Conditions
HIV coinfection, immunosuppression
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