Experimental Clostridium Welchii Infection: II. Local Sulfonamide Therapy (Sulfadiazine, Sulfathiazole and Sulfanilamide)

Abstract

Local sulfonamide therapy in C. welchii infection produced by intramusc. inoculation of mice was investigated. Sulfadiazine, sulfathiazole or sulfanilamide was administered in a suspension injd. subcut. or intramusc. into or near the infected area. The amts. of drug absorbed by the blood were plotted and compared with those obtained from peritoneal absorption. The best survival rates were obtained with sulfadiazine (49-57%) and sulfathiazole (40-53%); sulfanilamide was of little value. A delay of 1-2 hrs. in the institution of therapy markedly reduced the protective action. The rate of survival was as good with a 1 mg. as with a 50 mg. dose, but the extent of tissue injury was greater. Low concs. of the drugs in the blood produced by injecting the drug in the normal, uninfected leg, gave as much protection as high local concs. produced by injecting the drug directly into the infected area. Repeated injections of the drugs protected no better than a single injection. The lesions produced at the sites of inoculation were no different than those following oral therapy, and healing seemed to be dependent upon the speed and extent of sloughing of the dead tissues. Injection of the drug 3 hrs. before inoculation produced results comparable to the previously reported survival rates obtained with oral therapy. They confirmed the earlier suggestion that the excellent results were due to the combined effect of prophylaxis and active therapy. Sulfonamides, administered early, have a definite therapeutic effect upon C. welchii infection. They are of greatest value in prophylaxis and early treatment where they check the rapid extension of the infection and thus permit time for marshalling the defense mechanisms of the body until more adequate treatment (debridement) is possible. They are of considerable value but still leave much to be desired in the treatment of gas gangrene.