Existence in the blood of a new factor that intervenes in antibiotic therapy

Abstract
We liave carried out experiences with Kanamycin sulfate which was inyected to a series of rabbits according to WEST’s niethod with dosis of 10 mgrs. upto 200 mgrs. in total upto 450 mgrs. of Kanamycin/Kg. of rabbit, during a month. Thisamount was sufficient to provokes an immunological response able to be detected in the serum.
Intradermo-reactions to íind out, if any, the degree of sen- sibility to the drug were made with 0.15 mi. of standard Solu tions with 40, 20, 10, 5, 2.5, 1.25, 0.62 and 0.31 rnicro- grams/ml. Negative results were obtained.
The problem-serum and test-serum were set into the pre- sence of a range of increasing concentration of Kanamjrcin.The minimal inhibitory concentration was determined accor ding to the method of one of us (PORTOLES, 1960) against Sla- [ihyloooccus aureus.
Immunological test were made to learn about the possible carachter of this antibiotic action neutralizing substance :precipitaron tests on tube for Kanamycin dilutions (1 :1-1 :50.000) and serum; dilutions (1/2 to 1/60) were investigated, but with negative results. Furthermore, the deviation of com- plenient tests were made according to Zuazo’s technique (1958) with inactived serum (1:1 until 1 : 40) and Kanamycin from 2.5 up to 100 mgr/ml from which we obtained positive results ; but absolute negative ones by the anticomplementary tests of the antigen with 25 mgr. Kanamycin/mi.
The inactivating action may be seen in the Graph. 2, in which we notice the difference in M.I.C. between the problem serum and the test serum.
The deviation of complement tests were positive at titles of 1/5 of serum and 10 mgr/ml. as it is indicated in scale 1. The results of these experiments suggest the existence in the serum of antibiotic treated animáis, of a substance which inactivates specifically the antibiotic and acting proportionally to the time of contact (exposure).