A golden-hamster model of antimicrobial agent-associated lethal enterocolitis was produced by oral administration of cef atrizine (CFT). In all diarrheal and dead animals, the striking finding at necropsy was enterocolitis in which the cecum and distal ileum were greatly distended with fluid: toxigenic Clostridium difficile was detected at 108 CFU/head or greater. Bacteria-free cecal filtrate and culture filtrate of C. difficile isolated from the cecal contents of diarrheal animals exhibited lethal toxicity to normal hamsters. A single oral administration of CFT (75mg/kg) produced lethal enterocolitis in 17 of 20 animals during a one-month period of observation. Clostridium butyricum Miyairi (CbM), spores, used as an enteroregulator, were investigated for their potential to prevent the lethal enterocolitis in this model. Animals were administrated CbM orally (109 CFU/day) for three consecutive days after CFT challenge, and this prevented death in 16 of 20 animals during one mouth of observation. These results suggest that CbM has a preventive effect against lethal enterocolitis in this model.
Re-mutant lipopolysaccharide (Re LPS) of Salmonella minnesota profoundly inhibited the growth of murine B-cell lines, designated CYG34 and CYG101, established from long term bone-marrow culture. When CYG101 cells were cultured together with Re LPS at concentrations of 2-100μg/ml, the cell proliferation was dose-dependently suppressed. Re LPS hardly or slightly affected the growth of a murine T-cell line, BW5147, pre-B cell lines, 70Z/3 and CYG 8, and a myeloma cell line, X63Ag8. S-form LPS of Escherichia coli and S. typhimurium, Re-mutant LPS of S. minnesota and natural lipid A of E. coil, S. typhimurium and S. minnesota also inhibited the growth of CYG101 cells. However, degraded polysaccharide of S-form LPS of S. typhimurium did not inhibit the cell growth. Synthetic compounds 406, corresponding to a biosynthetic disaccharide lipid A precursor, and 506, corresponding to lipid A of the E. coli type, also inhibited the growth of CYG101 cells. These results suggest that the growth inhibition of cell lines by LPS is selective or specific to the cell line and that the lipid A portion of LPS is involved in this growth inhibition. Double acyl groups of lipid A may not play any role in the inhibition of cell growth.