292 DISEASE CONTROL 



Relatively little transfer of streptomycin occurs between the blood 

 and the lumen of the gastro-intestinal tract in either direction. Follow- 

 ing oral administration, levels as high as 9 mg. per gm. were found in 

 the feces. Because of the poor transfer of the drug across the walls of the 

 alimentary tract, it was suggested that the drug be used both orally 

 and parenterally in the treatment of infections such as those in which 

 the pathogenic organisms are found both in the gastro-intestinal tract 

 and in the blood stream (230, 393, 1049). 



When fed to mice in their diet streptothricin and especially strepto- 

 mycin produced a very rapid reduction in the numbers of colif orm and 

 nonlactose-fermenting organisms in the feces. The amount of strepto- 

 thricin required for effective reduction of the intestinal bacteria was 

 one-half the toxic dose. Due to the lower toxicity of streptomycin the 

 dose required was much below the toxic one and maintained the re- 

 duced number of organisms as long as therapy was continued. A distinct 

 change in the intestinal flora was thus produced without increasing the 

 resistance of the organisms (859). 



In order to produce toxic manifestations in animals, it is necessary to 

 administer either extraordinarily large amounts of the pure material or 

 smaller amounts of certain impure preparations containing a histamine- 

 like substance. No correlation was obtained between the acute toxicity 

 of different lots to experimental animals and clinical tolerance by 

 human beings. The behavior of the material in man cannot, therefore, 

 be foretold if antibacterial potency alone is assumed to be the criterion 

 of purity 5 highly concentrated material has on occasion been unsatis- 

 factory clinically, whereas considerably less active preparations have 

 often produced no undesirable effects. 



Two distinctly different types of toxicity are possible. One, which is 

 observed only with certain impure preparations, is due to a histamine- 

 like substance. The general syndrome produced in man consists essen- 

 tially of nausea, throbbing headache, general malaise, skin rash, pain 

 in the joints, flushed face, vomiting, and drug fever, the last appearing 

 two or three days after treatment and therefore not due to bacterial 

 pyrogen. Local reactions at the sites of injection have also been en- 

 countered. These toxic manifestations are entirely absent when crystal- 

 line streptomycin, as well as many impure preparations, are used. By 



