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Antimicrobial Agents and Chemotherapy, June 2008, p. 2190-2195, Vol. 52, No. 6
0066-4804/08/$08.00+0     doi:10.1128/AAC.00041-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Tolevamer, an Anionic Polymer, Neutralizes Toxins Produced by the BI/027 Strains of Clostridium difficile

Genzyme Drug and Biomaterial Research and Development, 153 Second Avenue, Waltham, Massachusetts 02451

Received 10 January 2008/ Returned for modification 11 February 2008/ Accepted 26 March 2008

Clostridium difficile-associated diarrhea (CDAD) is caused by the toxins the organism produces when it overgrows in the colon as a consequence of antibiotic depletion of normal flora. Conventional antibiotic treatment of CDAD increases the likelihood of recurrent disease by again suppressing normal bacterial flora. Tolevamer, a novel toxin-binding polymer, was developed to ameliorate the disease without adversely affecting normal flora. In the current study, tolevamer was tested for its ability to neutralize clostridial toxins produced by the epidemic BI/027 strains, thereby preventing toxin-mediated tissue culture cell rounding. The titers of toxin-containing C. difficile culture supernatants were determined using confluent cell monolayers, and then the supernatants were used in assays containing dilutions of tolevamer to determine the lowest concentration of tolevamer that prevented 90% cytotoxicity. Tolevamer neutralized toxins in the supernatants of all C. difficile strains tested. Specific antibodies against the large clostridial toxins TcdA and TcdB also neutralized the cytopathic effect, suggesting that tolevamer is specifically neutralizing these toxins and that the binary toxin (whose genes are carried by the BI/027 strains) is not a significant source of cytopathology against tissue culture cells in vitro.

Published ahead of print on 7 April 2008.