Binding of Clostridium difficile cytotoxin and vancomycin by anion-exchange resins.
Cholestyramine and colestipol were tested for binding of Clostridium difficile cytotoxin with use of batch absorption and column chromatography. The toxin was bound by both resins and could not be eluted from cholestyramine with either an ionic of a pH gradient. Vancomycin bound to cholestyramine more strongly than to colestipol. Cholestyramine and vancomycin were also tested for therapeutic efficacy in the hamster model of clindamycin-induced cecitis. Both compounds delayed death and reduced levels of cytotoxin in stool; these effects were greatest for vancomycin. Use of the two compounds in combination reduced concentrations of biologically active vancomycin in stool, but the levels still exceeded the minimum inhibitory concentration for C. difficile. These data suggest that the therapeutic benefit of cholestyramine in some patients with antibiotic-associated pseudomembranous colitis is due to its binding of the C. difficile cytotoxin. Since anion-exchange resins also bind vancomycin, caution is necessary if resins are used concurrently with vancomycin for therapy.
D000042:Absorption; D000818:Animals; D000837:Anion Exchange Resins / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D001667:Binding, Competitive; D002792:Cholestyramine Resin / Q000494:pharmacology / Q000627:therapeutic use; D002981:Clindamycin / Q000009:adverse effects; D003013:Clostridium / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D003084:Colestipol / Q000494:pharmacology; D006224:Cricetinae; D003603:Cytotoxins / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004761:Enterocolitis, Pseudomembranous / Q000139:chemically induced / Q000188:drug therapy; D005243:Feces / Q000378:metabolism / Q000382:microbiology; D007475:Ion Exchange Resins / Q000378:metabolism*; D008297:Male; D014640:Vancomycin / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*
D000837:Anion Exchange Resins; D000900:Anti-Bacterial Agents; D003603:Cytotoxins; D007475:Ion Exchange Resins; D002792:Cholestyramine Resin; D002981:Clindamycin; D014640:Vancomycin; D003084:Colestipol