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Oritavancin Demonstrates Superior In Vitro Activity to Vancomycin and Metronidazole Against C. Difficile Bacteria
Targanta Therapeutics Corporation today released data from two studies comparing the in vitro activity of its lead antibiotic drug candidate, oritavancin, to that of other antibiotics against Clostridium difficile bacteria. Results are being presented today at the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) taking place in Chicago, IL.
C. difficile are anaerobic, gram-positive, spore-forming bacteria that are a major cause of morbidity in the hospitalized elderly. C. difficile infection is associated with many diseases, the most significant of which are uncomplicated diarrhea and pseudomembranous colitis, or severe infection of the colon. Often, after normal gut flora are eradicated by the use of antibiotics, it is postulated that C. difficile spores refractory to current antimicrobial therapies persist, causing recurrent infections. The U.S. Centers for Disease Control and Prevention (CDC) reports that each year nearly 10 percent of all hospitalized patients, or two million patients, contract C. difficile infections during their stay.
In the first study, presented as a poster entitled "In Vitro Susceptibility of Genotypically Distinct Clostridium difficile Strains to Oritavancin," researchers tested the activity of oritavancin versus the standards of care, metronidazole and vancomycin, against 33 genotypically distinct strains of C. difficile bacteria. Overall, in this study, oritavancin was more active than either metronidazole or vancomycin, and oritavancin was more active than vancomycin against 94% of the C. difficile strains tested by the broth macrodilution method.
In the second study, accepted as a late-breaker poster presentation entitled "Activity of Metronidazole, Vancomycin and Oritavancin Against Epidemic Clostridium difficile Spores," researchers compared the activity of oritavancin, metronidazole and vancomycin against epidemic C. difficile spores using spiral gradient endpoint, agar-based culture, and phase contrast microscopy. Using these three different experimental methods, results from the study indicated that oritavancin interacts with and disrupts the transition from dormant C. difficile spores to vegetative cells to a greater extent than existing therapeutic antimicrobial agents. In addition, there was a marked difference in oritavancin activity against C. difficile spores versus vegetative cells (5- to 13-fold lower MICs against the spores); Targanta believes that such a phenomenon has not been reported previously.