The Remote Sustained Threshold Therapeutic Action of Streptomycin in Tuberculosis

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Abstract
One mg. of a suspension of a highly virulent strain of human tubercle bacilli (#4008) was injd. intraven. into guinea pigs. Using controls and also animals given 25,000 U. of streptomycin daily for 82-91 days and infecting them 1 day after the last treatment, the av. duration of life of the controls was found to be 22 days and that of the pretreated animals 29 days. When the pretreatment continued for only 2 wks., the av. duration of life of the controls was 21 days, and that of the pretreated animals was 22 days. The results of injn. of 4 doses of streptomycin daily for a total of 25,000 U. were compared with those of a single injn. of 25,000 U. daily and also with 25,000 U. given at 5 day intervals in a single injn. The av. duration of life of controls (without treatment) was 19-21 days, and that of animals given 4 daily injns. was 100-150 days. The duration of life of animals given injns. at 5 day intervals was > 100 days. In all expts., individual animals would die of a generalized tuberculosis despite treatment. The expts. indicate that there is a threshold of remote sustained action. When initiated minimally, the effect persists for some time; above the max. threshold effect, it is needless to continue forced treatment since the benefit does not exceed that of the established maximum.