IN-VITRO ACTIVITIES OF 2,2'-BIPYRIDYL ANALOGS AGAINST MYCOBACTERIUM-AVIUM AND MYCOBACTERIUM-TUBERCULOSIS

Setting: Because of widespread emergence of resistant Mycobacterium tuberculosis and the high incidence of opportunistic infection caused by M. avium complex (MAC) in AIDS patients, there is an urgent need for new drugs against these organisms. Objective: To evaluate the activity of newly synthesized 2'2-bipyridyl analogues against MAC and M. tuberculosis. Design: Susceptibility of MAC and M. tuberculosis to VUF-8514 and VUF-8842 were determined by both tube dilution method using 7H9 broth and radiometric (BACTEC) method using C-14-palmitic acid. Results and Conclusions: The MICs of 8514 against MAC and M. tuberculosis wee 1 mug/ml and 0.5 mug/ml respectively, while for 8842 the respective values were 8 mug/ml and 2 mug/ml. In general, the MBC values for both drugs were two-fold higher than their corresponding MIC values. However, both drugs exhibited high bactericidal activities against both organisms. The MICs of clinical isolates of both organisms were in the same range as reference strains; furthermore, two isolates of M. tuberculosis that showed resistance to rifampicin were found to be susceptible to 8514. Thus, these two bipyridyl analogues show great promise in chemotherapy of tuberculosis and M. avium infection.