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Drug Resistance in Tuberculosis
Author(s) -
Blanchard John Sears
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.307.1
Subject(s) - rifampicin , ethambutol , isoniazid , pyrazinamide , tuberculosis , medicine , drug resistance , drug , aminoglycoside , mycobacterium tuberculosis , antibiotics , pharmacology , microbiology and biotechnology , biology , pathology
Drug resistance is a common problem in all bacterial infections, but in the particular case of human Tuberculosis (TB), there are few effective drugs that have been developed and approved for use against the disease. Modern chemotherapy against TB consists of treatment for two months with four drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) followed by an additional four months with isoniazid and rifampicin. Significant resistance to isoniazid began to appear in the early 1980's, while the emergence of strains resistant to both isoniazid and rifampicin began to emerge in the 1990's. These are the two compounds that exhibit bactericidal activity against rapidly growing organisms, and strains exhibiting this resistance pattern are termed multi‐drug resistant (MDR). More recently, strains that are extremely‐drug resistant have been reported around the globe. These strains are resistant to both isoniazid and rifampicin, as well as fluoroquinolones and at least one aminoglycoside. These XDR‐TB strains are extremely difficult to treat effectively, and mortality rates are extremely high for persons infected with XDR‐TB. A large effort is currently underway to identify new lead compounds with novel targets and mechanisms of action. Several candidates in clinical trails will be discussed. In addition, a reexamination of drugs previously not used to treat TB is underway. The mechanisms of action of, and mechanisms of resistance to, both old and newly developing drugs will be discussed.