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Antimicrobial Agents and Chemotherapy, August 2001, p. 2340-2347, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2340-2347.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

GT160-246, a Toxin Binding Polymer for Treatment of Clostridium difficile Colitis

Caroline B. Kurtz,1,* E. Pat Cannon,1,dagger Alex Brezzani,1 Mary Pitruzzello,1 Carol Dinardo,1 Emilie Rinard,1 David W. K. Acheson,2 Richard Fitzpatrick,1 Pamela Kelly,1 Keith Shackett,1 Andrew T. Papoulis,1 Philip J. Goddard,1 Robert H. Barker Jr.,1 Gerard P. Palace,1 and Jeffrey D. Klinger1

GelTex Pharmaceuticals, Inc., Waltham, Massachusetts 02451,1 and Tufts University/New England Medical Center, Boston, Massachusetts 021112

Received 5 January 2001/Returned for modification 27 February 2001/Accepted 23 April 2001

GT160-246, a high-molecular-weight soluble anionic polymer, was tested in vitro and in vivo for neutralization of Clostridium difficile toxin A and B activities. Five milligrams of GT160-246 per ml neutralized toxin-mediated inhibition of protein synthesis in Vero cells induced by 5 ng of toxin A per ml or 1.25 ng of toxin B per ml. In ligated rat ileal loops, 1 mg of GT160-246 neutralized fluid accumulation caused by 5 µg of toxin A. At doses as high as 80 mg/loop, cholestyramine provided incomplete neutralization of fluid accumulation caused by 5 µg of toxin A. GT160-246 protected 80% of the hamsters from mortality caused by infection with C. difficile, whereas cholestyramine protected only 10% of animals. Treatment of C. difficile-infected hamsters with metronidazole initially protected 100% of the hamsters from mortality, but upon removal of treatment, 80% of the hamsters had relapses and died. In contrast, removal of GT160-246 treatment did not result in disease relapse in the hamsters. GT160-246 showed no antimicrobial activity in tests with a panel of 16 aerobic bacteria and yeast and 22 anaerobic bacteria and did not interfere with the in vitro activities of most antibiotics. GT160-246 offers a novel, nonantimicrobial treatment of C. difficile disease in humans.

* Corresponding author. Mailing address: GelTex Pharmaceuticals, Inc., 153 Second Ave., Waltham, MA 02451. Phone: (781) 434-3477. Fax: (781) 895-4980. E-mail: ckurtz{at}geltex.com.

dagger Present address: Paratek Pharmaceuticals, Inc., Boston, MA 02111.

Antimicrobial Agents and Chemotherapy, August 2001, p. 2340-2347, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2340-2347.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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