Multi-drug resistant tuberculosis (MDR-TB), caused by M. tuberculosis resistant to bogh isoniazid and rifampicin (another treatment option) has become a recently large global concern. About 3 percent of new cases of tuberculosis are MDR-TB worldwide and the proportion is even higher in patients who have previously received anti-tuberculosis treatment. In the past three decades, drug resistance in the US has risen from 2 to 9 percent.
From 1993 to 1996 a study was published in the Journal of American Medicine Association, that concluded that overall resistance to isoniazid among patients responding to the national surveilance program to was 8.4 percent.
The mechanism of resistance to M. tuberculosis is unknown. However two studies have recently revealed new knowledge on INH resistance. Most of the studies conducted on the mechanism of action of INH have tried to incorporate possible reasons for resistance, but none have been succesful at determining the primary mechanism.
A study conducted in New York City demonstrated that 90 percent of INH sensitive and 76 percent of INH resistant clinical isolates of M. tuberculosis contained the sequences katG. 78 percent of these 41 resistant strains expressed the enzyme catalase. While this does not explain the mechanism of resistance fully, the frequency of this result is interesting.
Another study by Banerjee et al. identified the gene inhA, a substitution of Ser to Ala at position 94 in INH resistant strains of M. smegmatis and M. bovis- BCG. It suggests that InhA is a target of Mycolic acid synthesis. This result has also been observed in clinical isolates. Over expression of the InhA protein shows that this finding may have clinical relevance as well.