Intestinal beta-lactamase activity in ampicillin-induced, Clostridium difficile-associated ileocecitis.
Daily oral administration of ampicillin to hamsters consistently resulted in fatal ileocecitis due to ampicillin-susceptible strains of Clostridium difficile. Ampicillin was not detected in the cecal contents of these hamsters once C. difficile appeared. Cecal contents obtained from hamsters with ampicillin-induced ileocecitis displayed beta-lactamase activity, whereas cecal contents obtained from untreated control hamsters did not. Colonization of the ceca with C. difficile corresponded to a decrease in the concentration of cecal ampicillin below the minimum inhibitory concentration effective against C. difficile in vitro. The concomitant administration of ampicillin and sulbactam, a nonabsorbable beta-lactamase inhibitor, protected hamsters from developing fatal ileocecitis. However, ileocecitis developed upon the discontinuation of treatment. beta-Lactamase produced by the cecal flora inactivates ampicillin present in the intestinal tract, thereby permitting ampicillin-sensitive C. difficile to multiply and cause disease.
D000667:Ampicillin / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D002429:Cecal Diseases / Q000201:enzymology* / Q000209:etiology; D003013:Clostridium / Q000187:drug effects; D003015:Clostridium Infections / Q000201:enzymology*; D006224:Cricetinae; D007079:Ileitis / Q000201:enzymology* / Q000209:etiology; D007249:Inflammation / Q000209:etiology; D007422:Intestines / Q000201:enzymology*; D008297:Male; D008647:Mesocricetus; D001618:beta-Lactamases / Q000032:analysis*
D000667:Ampicillin; D001618:beta-Lactamases