Clofazimine and other rimino-compounds: minimal inhibitory and minimal bactericidal concentrations at different pHs...

Clofazimine (Lamprene, B663) and 11 rimino-compounds were tested for activity against Mycobacterium avium by finding the minimal inhibitory concentrations (MIC) of these drugs in liquid medium. The activity of these compounds was affected in acidic conditions (pH 6.0 and 5.0), but the MICs observed even at pH 5.0 were significantly lower than the concentrations achievable in macrophages. This information is especially useful in the light of four important facts: that these drugs tend to accumulate within macrophages; that M. avium tends to multiply within macrophages; that this intracellular environment has a low pH; and that M. avium tolerates these low pH conditions. Such data confirm the expectation that rimino-compounds inhibit the intracellular M. avium bacterial population. The minimal bactericidal concentrations (MBC) of clofazimine and B746, the most active analogue, were from 64 to 256 times higher than the MIC, but it is not clear whether these drugs can accumulate within the macrophages in concentrations high enough to produce the bactericidal effect as well.