Wednesday, August 31, 2011

Antibiotics Resistance of Mycobacterium tuberculosis

Shortly after the first anti-tuberculosis (TB) drugs were introduced, streptomycin (STR), para-aminosalicylic acid (PAS), isoniazid (INH) resistance to these drugs was observed in clinical isolates of Mycobacterium tuberculosis (Crofton and Mitchison, 1948). This led to the need to measure resistance accurately and easily. The Pasteur Institute introduced the critical proportion method in 1961 for drug susceptibility testing in TBand this method became the standard method of use (Espinal, 2003). Studies on drug resistance in various countries in the 1960s showed that developing countries had a much higher incidence of drug resistance than developed countries (Espinal, 2003). By the end of the 1960s rifampicin (RIF) was introduced and with the use of combination therapy, there was a decline in drug resistant and drug susceptible TB in developed countries. This led to a decline in funding and interest in TB control programs.

As a result, no concrete monitoring of drug resistance was carried out for the following 20 years (Espinal, 2003). The arrival of HIV/AIDS in the 1980s resulted in an increase in transmission of TB associated with outbreaks of multidrug-resistant TB (MDR-TB) (Edlin et al., 1992; Fischl et al., 1992) i.e. resistant to INH and RIF. In the early 1990s drug resistance surveillance was resumed in developed countries, but the true incidence remained unclear in the developing world (Cohn et al., 1997).
Any drug used in the anti-TB regiment is supposed to have an effective sterilizing activity that is capable of shortening the duration of treatment. Currently, a four-drug regiment is used consisting of INH, RIF, pyrazinamide (PZA) and ethambutol (EMB). Resistance to first line anti-TB drugs has been linked to mutations in at least 10 genes; katG inhA, ahpC, kasA and ndh for INH resistance; rpoB for RIF resistance, embB for EMB resistance, pncA for PZA resistance and rpsL and rrs for STR resistance.

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