RELATION OF THE SIZE OF THE INOCULUM AND THE AGE OF THE INFECTION TO THE CURATIVE DOSE OF PENICILLIN IN EXPERIMENTAL...

1. A relatively small amount of penicillin sufficed to abort syphilitic infection in rabbits when administered during the incubation period of the disease. 2. The abortive dose, given as a single intramuscular injection in oil and beeswax, varied with the age of the infection. (a) With a fixed intratesticular inoculum, the amount of penicillin necessary to prevent infection in half the animals remained at a constant level for 4 days. By the end of the 2nd week more than seven times this dosage was needed; and by the 6th week, after the chancre had appeared, more than thirty times the amount was needed to obtain the same result. The progressive increase in the abortive dose of penicillin with the passage of time probably reflects the interim multiplication of organisms. (b) Qualitatively similar results were obtained in rabbits inoculated intracutaneously. 3. The abortive dose varied also with the size of the inoculum. In animals inoculated intracutaneously with 20, 2,000, and 200,000 spirochetes, and treated 4 days later, it required 200, 500, and 3,500 units per kg., respectively, to protect half the animals, and the corresponding PD(90) dosages were 500, 2,000, and 16,000 units per kg. 4. The present observations, indicating the ease of aborting experimental rabbit syphilis during the incubation period by a single injection of penicillin, are perhaps applicable to the prevention of the disease in man. 5. Asymptomatic infections were rare in animals receiving inadequate doses of penicillin during the incubation period. Sixty-four of sixty-five such animals developed darkfield-positive lesions at the inoculated site. In animals treated 6 weeks after inoculation, however, after the development of lesions, inadequate treatment was usually manifested by an asymptomatic redissemination of organisms demonstrable only by lymph node transfer. The difference in the two groups probably reflects the beginning development of immunity in the rabbits treated 6 weeks after inoculation. 6. As suggested by Rake and Dunham (11), the treatment of animals during the incubation period permits a rapid assay of antisyphilitic agents, and one which requires only small amounts of material. Possible limitations of the method are discussed in the text.