Molecular basis of drug resistance in Mycobacterium tuberculosis

In 2011, the World Health Organization (WHO) reported nearly 60,000 new cases of multidrug-resistant tuberculosis (MDR-TB) (1), and estimates of the annual global incidence are much higher. The emergence of drug-resistant strains has made the treatment of TB complex, costly, toxic, time-intensive, and less efficacious. Design of a treatment regimen for drug-resistant TB includes the administration of first-line drugs to which the strains remain susceptible together with second-line drugs. These second-line agents are more expensive, more difficult to administer (several require intravenous administration), and are often associated with severe toxicities, including hepatic and renal dysfunction. In comparison to the 6 months required to treat drug-susceptible TB, drug-resistant TB requires a prolonged treatment duration of 18 to 24 months. These logistics constitute considerable hardships for patients as well as for overburdened public health services. Too frequently, premature discontinuation of therapy occurs, leading to treatment failure and the emergence of Mycobacterium tuberculosis strains with additional drug resistance.