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In Vitro Activities of 15 Antimicrobial Agents against 110 Toxigenic Clostridium difficile Clinical Isolates Collected from 1983 to 2004

Loyola University Medical Center and Loyola University Stritch School of Medicine, Maywood, Illinois,¹ Edward Hines Jr. Veterans Affairs Hospital, Hines, Illinois²

Received 28 December 2006/ Returned for modification 1 March 2007/ Accepted 14 May 2007

The incidence and severity of Clostridium difficile-associated disease (CDAD) is increasing, and standard treatment is not always effective. Therefore, more-effective antimicrobial agents and treatment strategies are needed. We used the agar dilution method to determine the in vitro susceptibility of the following antimicrobials against 110 toxigenic clinical isolates of C. difficile from 1983 to 2004, primarily from the United States: doripenem, meropenem, gatifloxacin, levofloxacin, moxifloxacin, OPT-80, ramoplanin, rifalazil, rifaximin, nitazoxanide, tizoxanide, tigecycline, vancomycin, tinidazole, and metronidazole. Included among the isolates tested were six strains of the toxinotype III, NAP1/BI/027 group implicated in recent U.S., Canadian, and European outbreaks. The most active agents in vitro were rifaximin, rifalazil, tizoxanide, nitazoxanide, and OPT-80 with MICs at which 50% of the isolates are inhibited (MIC₅₀) and MIC₉₀ values of 0.0075 and 0.015 µg/ml, 0.0075 and 0.03 µg/ml, 0.06 and 0.125 µg/ml, 0.06 and 0.125 µg/ml, 0.125 and 0.125 µg/ml, respectively. However, for three isolates the rifalazil and rifaximin MICs were very high (MIC of >256 µg/ml). Ramoplanin, vancomycin, doripenem, and meropenem were also very active in vitro with narrow MIC₅₀ and MIC₉₀ ranges. None of the isolates were resistant to metronidazole, the only agent for which there are breakpoints, with tinidazole showing nearly identical results. These in vitro susceptibility results are encouraging and support continued evaluation of selected antimicrobials in clinical trials of treatment for CDAD.

Published ahead of print on 21 May 2007.

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