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Replidyne's Investigational Antibacterial Agent REP3123 Prevents Sporulation in Clostridium difficile
Date:9/19/2007

rganism from synthesizing proteins. Methionyl tRNA synthetase is a novel target that has not been previously exploited by antibiotics and REP3123 shows no cross-resistance to currently marketed antibacterial agents. To determine the ability of REP3123 to prevent sporulation of C. difficile, four clinical isolates were studied including two epidemic BI/NAP1/027 strains identified in recent outbreaks in Quebec, Canada. The BI/NAP1/027 outbreak strains produce greater amounts of toxins A and B, have increased sporulation capacity, and cause more severe disease and increased morbidity and mortality. All bacterial strains were grown in the presence of low concentrations (sub-minimum inhibitory concentrations or MICs) of either REP3123, vancomycin or metronidazole. Spores were quantified after 96 hours of drug exposure. All four strains of C. difficile varied in their ability to produce spores under the conditions evaluated in this study. At 0.5 times the MIC, REP3123 was the most effective agent at preventing the production of spores in all strains (equal to or less than 1% of spores after 96 hours of treatment). In contrast, sub-MICs of metronidazole promoted spore formation in three strains and vancomycin promoted sporulation in two strains. The ability of REP3123 to inhibit sporulation was concentration-dependent, with no spores detected at concentrations of 0.5 times the MIC. The FDA has not approved REP3123 for marketing in this or any other indication.

"CDAD is a challenging disease for many reasons, including the difficulty associated with eradication of Clostridium difficile and its spores from the environment," explained Stuart Johnson, M.D., Associate Professor of Medicine, Stritch School of Medicine, Loyola University and the Hines VA Medical Center in Chicago. "These results demonstrating that REP3123 has a direct impact on inhibiting spore-formation of C. difficile bacteria are highly promising and clinically relevant."

"Through a novel mechanism
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SOURCE Replidyne, Inc.
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