Intestinal β-Lactamase Activity in Ampicillin-Induced, Clostridium difficile-Associated Ileocecitis

• Published in: The Journal of infectious diseases Vol. 147; no. 2; pp. 227 - 235
• Main Authors: Rolfe, Rial D., Finegold, Sydney M.
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 01-02-1983; University of Chicago Press
• Subjects: Ampicillin - adverse effects; Ampicillin - pharmacology; Anaerobic bacteria; Animals; Antimicrobials; beta-Lactamases - analysis; Cecal Diseases - enzymology; Cecal Diseases - etiology; Clostridium - drug effects; Clostridium difficile; Clostridium Infections - enzymology; Colitis; Cricetinae; Cytotoxins; Diarrhea; Experimental Enteric Infections; Hamsters; Human resources; Ileitis - enzymology; Ileitis - etiology; Inflammation - etiology; Intestinal diseases; Intestines - enzymology; Male; Mesocricetus; Microbiology
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/147.2.227

Daily oral adminstration 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 β-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 β-lactamase inhibitor, protected hamsters from developing fatal ileocecitis. However, ileocecitis developed upon the discontinuation of treatment. β-Lactamase produced by the cecal flora inactivates ampicillin present in the intestinal tract, thereby permitting ampicillin-sensitive C. difficile to multiply and cause disease.