Antagonism between dapsone and rifampicin in experimental Mycobacterium leprae infections in mice

In experimental infections of normal mice with Mycobacterium leprae, the bactericidal activity of four consecutive weekly doses of rifampicin (RMP) was suppressed when this treatment was preceded, for one month, by daily administration of dapsone (DDS), and then the latter. Up until now, it has been impossible to detect this antagonism between the action of RMP and DDS, since all studies involved the simultaneous administration of these two drugs, and such a phenomenon would therefore have been masked by the rapid and potent action of RMP. Previous clinical observations suggest that such a delayed antagonistic effect may also occur in humans. The demonstration of this antagonism between RMP and DDS raises the problem of the long-term efficacy of therapeutic regimens currently used in leprosy and that of the role of DDS in induction of bacillary persistence. It is suggested that this particular methodology, the delayed combination of RMP with a less active drug, should be applied to the study of other drug combinations recommended in the treatment of leprosy.