STUDIES OF BACILLARY POPULATIONS IN EXPERIMENTAL TUBERCULOSIS OF MICE TREATED BY ISONIAZID

Abstract

A quantitative and qualitative study of populations of tubercle bacilli isolated from the lungs of mice during delayed treatment with isoniazid was carried out. Infection was producedby 2 strains of isoniazid -susceptible bacilli. Treatment commenced 14 days after infection. One-half of the animals were treated by a daily dose of 0.1 mg of isoniazid, and the other half by a dose of 1 mg. Treatment lasted 140 days. With the small dose of isoniazid, a relatively slow and late fall of the susceptible part of the bacillary population, and a still later fall of the fractions of the populations resistant to 0.05 [mu]g per ml and 0.1 [mu]g per ml, were observed. In some animals, a notable increase of the highly resistant fraction of the population ( >25 [mu]g per ml) occurred. With the large dose of isoniazid, an early and rapid fall of the susceptible population and the fractions of weakly resistant populations were observed. The increase of the highly resistant fraction occurred earlier, but was not significantly more important than in the animals treated with a small dose of isoniazid. The evolution of the populations has also been studied in relation to the concentration of active isoniazid present in the blood serum of the animals 2 hours after administration of the corresponding doses of isoniazid.