Evidence is given that for penicillin to prevent experimental tetanus in mice a 4-day period of treatment is satisfactory. To prevent tetanus by passive immunisation the antitoxin must remain in the circulation for 9 days. In either case frequently survives at the injection site. To account for these observations it is suggested that when tetanus bacilli grow in an anaerobic lesion, the local conditions are altered so that the time for which the lesion remains suitable for multiplication of anaerobic bacteria is prolonged. This conclusion is supported by the following findings.

() The extent of the anaerobic lesion produced by intramuscular injection of calcium chloride in guinea-pigs is increased about 10-fold when tetanus spores are also injected.

() Culture and histological examination of lesions in guinea-pigs at 9 days after injection of spores in calcium chloride showed the presence of numerous vegetative organisms but very few spores.

() A long-acting penicillin preparation was able to reduce the dose of antitoxin required to protect infected mice when the antibiotic was given either at 15 hr or 4 days after infection.

It is suggested that antibiotic may be of value in supporting the effect of antitoxin in prophylaxis in man, particularly in patients who may rapidly eliminate the heterologous horse serum, because it may reduce the time period for which the passive immunity is required.


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