| 摘要 |
Multidrug resistance to anti-tuberculous drugs poses threat in the treatment of tuberculosis. These strains are resistant to at least two first line anti-tuberculous drugs such as INH and rifampicin. Frequently, such MDR strains show resistance to all commonly used first-line agent i.e. INH, rifamcpicin, streptomycin, ethambutol and pyrazinamide. Isoniazid is the most widely used anti-tuberculous drug. Resistance to isoniazid can occur by increased expression in inhA or by mutations that lower the enzyme's affinity to NADH. Mutations in katG, which encodes catalase peroxidase, is the most common source of resistance. Another mechanism of isoniazid resistance occurs by defects in NADH dehydrogenase (Ndh) of the respiratory chain. Increases expression of AphC has been suggested as another mechanism of INH resistance in mycobacteria. The present invention overcomes INH resistance by the use of penicillins with INH. According to present invention, penicillins when used in effective amount, reduces the MIC of INH in multi-drug resistant strains of M. tuberculosis. The improved INH sensitivity, as brought by the present invention, falls within the range which can be exploited for effective therapeutic intervention. |
