EVALUATION OF ORAL, INTRAVENOUS, AND INTRAMUSCULAR AUREOMYCIN AND THE CORRELATION BETWEEN THE IN VIVO AND IN VITRO ACTIVITY

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Abstract
Mice were given a single intramusc. injn. of aqueous penicillin G or aureomycin and challenged either immediately or after 1-7 days with 10,000 M.L.D. of type I pneumococci. The rate at which the pneumococci were killed in the blood stream was detd. at varying intervals by bacterial counts obtained from a drop of tail blood. A single intramusc. injn. of 1 mg. of aqueous penicillin G, followed by immediate challenge, effected a prompt reduction in the bacterial count, but after 10 hrs. the count rose sharply and the mice died. Mice given 1 mg. of aureomycin intramusc. and challenged immediately, or even after 24 hrs., survived. Mice were then given single intramusc. injn. of 2, 3, or 4 mg. of aureomycin and challenged after 2 to 7 days. With increase in the dose of aureomycin there was a prolongation of the therapeutic effect. Two mg. markedly protected mice when challenged after three days, 3 mg. after four days and 4 mg. protected mice to a significant degree when challenged six days later. Mice given a single dose of 5 mg. orally or 2 mg. in- travenously, though challenged immediately, were not significantly protected. It is concluded that a single large dose of aureomycin given intramusc. to mice, though obviously painful, is slowly released from the site of injn. with the maintenance of a prolonged therapeutic blood level. Aureomycin blood levels were also detd. on the mice and it was found that the concn. of aureomycin required to inhibit growth of the pneumococcus in the mouse was 1/5 to 1/10 the concn. required to inhibit growth in various broth media in 18-20 hrs. at 37[degree]C. It is considered therefore that the recorded in vitro sensitivities of bacteria to aureomycin based on incubation at 37[degree]C for 18-20 hrs. give sensitivity figures that are 5-10 times too high by reason of the heat lability of aureomycin when in soln.
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