Activity of 2-acetylpyridine and 2-acetylquinoline thiosemicarbazones tested in vitro in combination with other antituberculous drugs.

Determinations of minimal inhibitory concentrations (MIC) were carried out using three new 2-acetylpyridine and two new 2-acetylquinoline thiosemicarbazones tested against Mycobacterium tuberculosis, M. kansasii, M. simiae, M. avium, and M. intracellulare. Two of the compounds (Compounds L and 3I) exhibited MIC less than or equal to 5 micrograms per ml for all of the test organisms, except for M. simiae, which was resistant to most antituberculous drugs. The other thiosemicarbazones (Compounds 3L, 2N, 3G, and 2H) were relatively inactive against the nontuberculous mycobacteria. Rifampin, amikacin, and clofazimine were active when tested singly or in combination with Compounds L and 3I. Addition of compound 3I to a mixture of rifampin, amikacin, and clofazimine resulted in combination MIC of less than 0.6 microgram/ml against all of the nontuberculous mycobacteria, suggesting that combinations of this type may be suitable for the treatment of infections caused by these highly drug-resistant organisms.