Toxin-binding treatment for Clostridium difficile: a review including reports of studies with tolevamer.
Clostridium difficile represents an increasing threat to patients, mainly as a hospital-acquired infection causing antibiotic-associated colitis (AAC). The emergence of a new more virulent strain in North America and Europe has been linked to increased morbidity and mortality. For a long period of time the only available therapeutic options were oral vancomycin and metronidazole. However, both of these antibiotics have limitations either in terms of efficacy, cost, formulation, side effects or the risk of emerging antibiotic resistance among enterococci. Clostridium difficile produces two powerful toxins (A and B) that are responsible for the entire clinical spectrum associated with AAC. As this is exclusively a toxin-mediated disease, agents with the potential of binding these targets have been tested. Data on polymer-based toxin-binding agents such as cholestyramine, Synsorb 90 and tolevamer, designed to target specific bacterial toxins, will be reviewed. Bovine colostrum and specific human monoclonal antibodies aimed at neutralising toxin A, although still at an early stage of development, are also new avenues to be explored. Non-antibiotic-based therapies might become the best available option for a condition almost always caused by antibiotics.
Weiss
Karl
K
Department of Microbiology and Infectious Diseases, Maisonneuve-Rosemont Hospital, Faculty of Medicine, Université de Montréal, 5415 l'Assomption, Montreal, Quebec, Canada H1T 2M4. weisscan@aol.com
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D002417:Cattle; D002648:Child; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D016360:Clostridioides difficile / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy* / Q000382:microbiology; D004768:Enterotoxins / Q000378:metabolism*; D006801:Humans; D011108:Polymers / Q000378:metabolism / Q000627:therapeutic use; D013451:Sulfonic Acids; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D011108:Polymers; D013451:Sulfonic Acids; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; C077114:styrenesulfonic acid polymer