It has been shown in a number of experimental infections1 that the amount of penicillin necessary for cure increases with the number of organisms inoculated. Thus, in white mice infected with pneumococci, the single curative dose of aqueous penicillin G increased in one experiment from 5 to 260 mg. per kilogram of body weight as the inoculum was increased from 15 to 200,000 organisms.1c
Corollary to these observations, it was found that the longer the interval between inoculation and treatment, the more drug was required for cure. Presumably because of the interim multiplication of organisms, effectively bactericidal levels had to be provided for longer and longer aggregate periods in order to kill enough of the bacteria to effect cure. In syphilitic rabbits, the 50 per cent curative dose of penicillin (in oil and wax) 4 hours after intratesticular inoculation with 2,000 organisms was 1,420 units per kilogram of