GT160-246, a toxin binding polymer for treatment of Clostridium difficile colitis.

Abstract

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 microg of toxin A. At doses as high as 80 mg/loop, cholestyramine provided incomplete neutralization of fluid accumulation caused by 5 microg 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.

• Authors: C B Kurtz, E P Cannon, A Brezzani, M Pitruzzello, C Dinardo, E Rinard, D W Acheson, R Fitzpatrick, P Kelly, K Shackett, A T Papoulis, P J Goddard, R H Barker Jr, G P Palace, J D Klinger
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 45 Issue 8 Pg. 2340-7 (Aug 2001) ISSN: 0066-4804 [Print] United States
• PMID: 11451694 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Bacterial Toxins
• Enterotoxins
• Ions
• Lactams
• Polymers
• Sulfonic Acids
• tcdA protein, Clostridium difficile
• toxB protein, Clostridium difficile
• Cholestyramine Resin
• Metronidazole
• styrenesulfonic acid polymer

Topics

• Animals
• Bacterial Proteins (antagonists & inhibitors)
• Bacterial Toxins (metabolism)
• Chlorocebus aethiops
• Cholestyramine Resin (therapeutic use)
• Clostridioides difficile (physiology)
• Clostridium Infections (drug therapy, metabolism, microbiology)
• Colitis (drug therapy, metabolism, microbiology)
• Cricetinae
• Enterotoxins (metabolism)
• Humans
• In Vitro Techniques
• Ions (metabolism, pharmacology, therapeutic use)
• Lactams (pharmacology)
• Male
• Metronidazole (therapeutic use)
• Microbial Sensitivity Tests
• Polymers (metabolism, pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Sulfonic Acids
• Survival Rate
• Vero Cells (microbiology)