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Abstract
The sensitivity of three strains of Mycobacterium leprae to dapsone (DDS) and rifampicin (RMP), administered continuously in the diet, was determined in the mouse footpad system. All three strains were inhibited by 0.0001 per cent. DDS. Sensitivity to RMP varied, the minimum inhibitory dose (MID) being 0.001 per cent, for two strains and 0.0003 per cent, for the third.
During the administration of 0.01 per cent. RMP, the concentrations of RMP in mouse serum, estimated by microbiological assay, was relatively constant at about 6 pg per ml over a 66-day period. The considerations for assuming a linear relationship between dietary dosage and the resultant serum concentration are discussed. It is inferred that a minimum inhibitory dose of RMP for M. leprae of 0.001 per cent, is equivalent to a minimum inhibitory concentration for the organism of 0.3 μg per ml.
The bactericidal action of DDS and of RMP on M. leprae was assessed by means of the kinetic technique of Shepard. The DDS treatment used apparently had no significant bactericidal effect. The bactericidal action of RMP was found to be relatively high, confirming the previous finding of Rees et al. in patients with lepromatous leprosy. Complete killing of M. leprae was obtained after 30 days’ treatment with 0.01 per cent. RMP in the diet (equivalent to a serum concentration of about 5 μg per ml). The relationship between the concentration of RMP in the serum of mice and its bactericidal action on M. leprae appears to be very similar to the corresponding relationship found in patients treated with the drug.
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