Alteration of the Distribution and Excretion of Streptomycin.

Abstract

Phagocytosis of colloidal particles by the reticulo-endothelium and the localization of such particles in inflamed areas under certain conditions are well known phenomena. These processes apparently depend upon several factors, among which are (a) charge of the particle, (b) particle size, and (c) capillary permeability. It has been observed that penicillin and streptomycin, while effective in eliminating the septicemic phase of certain diseases, fail to provide a complete cure. In the light of previously reported evidence, indicating that liver and spleen levels of streptomycin remain negative while blood levels are within a therapeutic range, it might reasonably be supposed that therapeutic failure is due to in inability of the antibiotic to reach intra-cellularly contained etiologic agents. To test this supposition, intracellular introduction of streptomycin into the reticuloendothelial cells was attempted by combining the antibiotic with an electronegatively-charged colloid that could be phagocytized. Preliminary experiments consisted of injecting white Swiss mice intraperitoneally with a single dose of a mixture containing 1000 “S” units of streptomycin and 20 mg of an elecetronegatviely-charged dye, trypan blue, in 1 ml of water. The mixture was adjusted to pH 7.4. (In contrast to streptomycin per se, this mixture of antibiotic and colloid did not dialyze through a cellophane membrane over a period of 24 hours). Three control groups of animals received respectively (a) 1000 “S” units of the antibiotic dissolved in 1 ml of distilled water, (b) 20 mg of the colloid supended in 1 ml distilled water, and (c) 1 ml of distilled water. Blood and organs rich in reticulo-endothelial tissue were assayed for the presence of the antibiotic one, 4, 8, and 25 hours after the injection. The average results are presented in Table I.