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FYI"Rifalazil Cures Clostridium difficile Diarrhea in Animal Model NEW YORK (Reuters Health) Nov 04 - The antibiotic rifalazil cures Clostridium difficile-associated diarrhea in hamsters, and may surpass vancomycin in its ability to prevent relapse, according to a report in Antimicrobial Agents and Chemotherapy for October.C. difficile is the most common cause of infectious nosocomial diarrhea, and is associated with disruption of normal colonic microflora following antibiotic treatment. The treatments of choice are metronidazole, which is associated with significant side effects, and vancomycin, which is costly and associated with the spread of vancomycin-resistant enterococci. Both drugs are associated with a high rate of relapse after discontinuation.Dr. Charalabos Pothoulakis, at Harvard Medical School in Boston, and colleagues injected Syrian hamsters with clindamycin then 24 hours later infected them with C. difficile by gavage. Vehicle-treated animals became moribund after 2 ays and were sacrificed. They exhibited acute lesions in the cecal mucosa, along with heavy congestion and edema.A second group of animals was treated with rifalazil, either simultaneously with C. difficile administration (prophylactic protocol) or 24 hours later (treatment protocol), which was continued for 5 days.None of the animals showed signs of disease, and they began gaining weight once treatment was discontinued, with no signs of relapse for up to 34 days. Histologic examination of ceca showed absence of epithelial cell damage and significantly reduced congestion and edema.In contrast, animals treated with vancomycin for 5 days began losing weight after treatment was discontinued. Of 14 animals, 65% died within 14 to 24 days after the C. difficile challenge. Microscopic examination revealed no protection from epithelial cell damage and only mildly reduced congestion and edema.C. difficile toxins A and B were detected in feces of five of eight vancomycin-treated hamsters but in none of five treated with rifalazil.These results strongly suggest that rifalazil could be used as a first-line therapeutic or prophylactic agent for treating C. difficile infection, Dr. Pothoulakas's group maintains, and may be superior to vancomycin, and possibly to metronidazole.Antimicrob Agents Chemother 2004;48:3975-3979.
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