Efficacy of different regimens in multibacillary leprosy.

The necessity for combined chemotherapy in multi bacillary leprosy has been recognized for about 1 5 years . I-3 It was however entirely unknown how this combined therapy had to be applied, particularly in respect to the drugs to be given, the frequency of their administration and above all the duration of therapy. We have approached the problem on the basis of results obtained in experimental chemotherapy of Mycobacterium leprae infections in mice,41 2 observations made in man 1 31 5 and prospective chemotherapeutic trials in patients . 16-1 9 From studies in mice and man, we know that there are a t present two bactericidal drugs: rifampicin (RMP) and the thioamides (either ethioor prothionamide, ETH or PRO), and two mainly bacteriostatic drugs : dapsone (DDS) and clofazimine (CLO) . RMP is extremely bactericidal, killing about 5 logs of M. leprae after a single dose of 1 500 mg or a few doses of 600 mg. Due to its profound effect on M. leprae, it can also be given intermittently up to once a month8 whereas ETH or PRO when administered less than three times a week, are inactive.9 , l o Dapsone and clofazimine are interchangeable as bacteriostatic drugs, and since they have a different action mechanism they do not show cross-resistance . From what was known in the treatment of tuberculosis, we concluded that what was needed for the treatment of M B leprosy was l ,2 an association of two and preferably three, bactericidal drugs (but only two are available in leprosy) in order to obtain maximal killing of M. leprae; and the addition of a bacteriostatic drug, whose main role would be to prevent the selection of organisms resistant to the bactericidal drugs. In this interpretation of the events occurring during chemotherapy, the use of a second bacteriostatic drug was unnecessary . We therefore used in all our trials DDS in new patients and replaced it by CLO in patients at risk for secondary DDS-resistance, defined as those patients who had been treated with DDS for 5