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Bacterial septicemia is frequently occurring during gastroenterological surgery. Because of increasing problems in hospitals with bacteria developing multiresistance against antibiotics, prophylactic treatment using immunomodulators is interesting. We have examined the putatively anti-infective immunomodulatory action of the edible mushroom, Agaricus blazei Murill (AbM), in an experimental peritonitis model in BALB/c mice. The mice were orally given an extract of AbM or phosphate-buffered saline 1 day before the induction of peritonitis with various concentrations of feces from the mice. The state of septicemia, as measured by the number of colony-forming units of bacteria in blood, and the survival rate of the animals were compared between the groups. Mice that were orally treated with AbM extract before bacterial challenge showed significantly lower levels of septicemia and improved survival rates. Our findings suggest that the AbM extract, when given prophylactically, may improve health. Further studies are needed on humans when considering whether AbM could be used as an alternative treatment modality for patients at risk of contracting serious bacterial peritonitis.