In vivo activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with dapsone, against Mycobacterium leprae

The antimicrobial effects of a new dihydrofolate reductase inhibitor, epiroprim, either singly or in combination with dapsone against Mycobacterium leprae, were evaluated in vivo using a mouse footpad model. When fed to mice at concentration of 0.05% in diet, epiroprim completely inhibited the growth of both dapsone-sensitive and dapsone-resistant strains of M. leprae in the footpads of mice and the effects were bactericidal. To achieve similar effects, the concentration of dapsone in the diet had to be 0.0005 and 0.01%, respectively. When used in combination, the concentrations of the drugs in the diet could be lowered by 50–80% and still achieve bactericidal effects. The data support the earlier results on in vitro studies and suggest the use of epiroprim in the multidrug regimen in the treatment of leprosy.