Intermittent chemotherapy of experimental leprosy in mice

In this study we assess the degree of prolonged bacteriostasis of Mycobacterium leprae after temporary exposure to ehtionamide or thiacetazone, and relate this to their efficacy when administered intermittently to mice with experimental leprosy infections. The results show that temporary exposure of M. leprae to either of these drugs results in a prolonged bacteriostatic effect, but that efficacy is rapidly lost as the interval between doses is increased. Using the mouse foot pad system, growth of M. leprae is not inhibited by thiacetazone when the frequency of administration is less than three times weekly. When ethionamide is administered once weekly, growth of M. leprae is inhibited but bactericidal activity is lost. When ethionamide is administered in combination with continuous dapsone therapy, either continuously or three times weekly, the bactericidal activity of the drug combination is greater than when either drug is administered alone. However, when ethionamide is administered once weekly in combination with continuous dapsone treatment, the bactericidal effect is identical to that when dapsone is given alone: that is, ethionamide makes no contribution to the combination.