STUDIES ON THE CLOSTRIDIAL TOXIN ASSOCIATED WITH ANTIBIOTIC-INDUCED PSEUDOMEMBRANOUS COLITIS

ABSTRACT The toxin of Clostridium difficile is considered responsible for pseudomembranous colitis which may follow antibiotic chemotherapy, This toxin can be produced in broth culture. After purification by gel filtration, ammonium sulfate precipitation, and ion-exchange chromatography, 12.5 picograms protein was cytotoxic to Chinese hamster ovary cells. Gnotobiotic rats were associated with a strain of C. difficile which produced large amounts of toxin. A spontaneous mutant was isolated from the ceca of these mice that produced 10,000-fold less toxin. This toxin had the same molecular weight as that produced by the parent and was neutralized by antitoxin to C. difficile . We have produced antitoxin to C. difficile that will neutralize the mouse LD 100 (ip, 16 h) of the toxin at a dilution of 1:8000.