Experiments were carried out to study the effect of chemotherapy in experimental tuberculosis. Mice were given intravenously a strain H37Rv of human type Mycobaterium tuberculosis, and chemotherapy was started either immediately or 3 weeks after the infection. The size of the dose varied from group to group, and the dosage schedules with animals in each group. The animals were divided into 7 groups following the infection, and 5 mg./kg, of isoniazid, 1 mg./kg, of isoniazid, 5 mg./kg, of isoniazid combined with 200mg./kg, of PAS, 5 mg./kg, of isoniazid combined with 50mg./kg, of PAS, 1 mg./kg, of isoniazid combined with 200mg./kg, of PAS, and 1 mg./kg, of isoniazid combined with 50mg./kg, of PAS were given except to one group, which was given no treatment and which served as the control. In each group, the specified amount of drug or drugs were
orally administered erey day, once or twice a week for a period of 100 consecutive days. The determination of the effect of treatment was based on the results of pathologic examination of the lungs and spleen, as well as cultures from them, which were obtained immediately, 4 weeks and 8 we eks after termination of the treatment. Administration of 5 mg./kg, of isoniazid every day had an effect; the specimens were negative for tubercle bacilli on culture immediately after termination of the treatment, but they became positive after 4 weeks, with an accentuation of the histologic picture. Administration of 5 mg/kg of isoniazid twice a week or of 1 mg./kg, of it every day prevented the growth and multi-
plication of the organisms. Under this regimen, however, the specimens did not become negative for tubercle bacilli on culture, and the disease spread rapidly with time. Administration of 5 mg./kg, of isoniazid once a week or 1 mg./kg, of it twice or less often a week produced little effect. The effect of combined administration PAS was noticed only when the dose of isoniazid was small (1 mg./kg, every day). On the other hand, when its
dase was large, it was so effective as to make it impossible to assess the value of PAS used in combination and consequently to make the combined use of the data meaningless. here were scarcely any organisms developing resistance to the drugs in any group.
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