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

GT160-246, a high-molecular-weight soluble anionic polymer, was tested in v itro and in vivo for neutralization of Clostridium difficile toxin A and B activities. Five milligrams of GT160-246 per mi neutralized toxin-mediated inhibition of protein synthesis in Vero cells induced by 5 mug of toxin A p er mi or 1.25 ng of toxin B per mi. Tn ligated rat ileal loops, 1 mg of GT1 60-246 neutralized fluid accumulation caused by 5 mug of toxin A. At doses as high as 80 mg/loop, cholestyramine provided incomplete neutralization of fluid accumulation caused by 5 mug 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-inf ected hamsters with metronidazole initially protected 100% of the hamsters from mortality, but upon removal of treatment, 80% of the hamsters had rela pses and died. In contrast, removal of GT160-246 treatment did not result i n disease relapse in the hamsters. GT160-246 showed no antimicrobial activi ty 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 antibio tics. GT160-246 offers a novel, nonantimicrobial treatment of C. difficile disease in humans.