Clostridium difficile antitoxin neutralization of cecal toxin(s) from guinea pigs with penicillin-associated colitis

Within 3 to 5 days after an intramuscular injection of penicillin, a high percentage of guinea pigs died with an enterocolitis. Bacteria-free filtrates of cecal content from penicillin-treated guinea pigs were lethal for guinea pigs and mice. These filtrates also increased vascular permeability in the skin of rabbits and were cytopathic in the Y-1 adrenal cell tissue culture system. The tissue culture assay was the most sensitive of the bioassays for detecting the toxicity of the cecal filtrates. Clostridium difficile antitoxin neutralized all three biological effects, whereas Clostridium sordellii antitoxin did not prevent mice from dying when injected with a lethal dose of cecal filtrate. The neutralization patterns of the biological effects of these two antitoxins suggested Clostridium difficile toxin was responsible for the biological effects of the cecal filtrates. The neutralization patterns of these two antitoxins also indicated Clostridium difficile antitoxin should be used for definitive identification of Clostridium difficile toxin in cecal filtrates since Clostridium sordellii antitoxin did not neutralize all the biological effects of the cecal filtrates.