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Antimicrob. Agents Chemother. doi:10.1128/AAC.01623-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

In Vitro activity of Fifteen Antimicrobial Agents Against 110 Toxigenic Clostridium difficile Clinical Isolates Collected from 1983-2004

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

^* To whom correspondence should be addressed. Email: dhecht{at}lumc.edu.

	Abstract

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 US : doripenem, meropenem, gatifloxacin, levofloxacin, moxifloxacin, OPT-80, ramoplanin, rifalazil, rifaximin, nitazoxanide, tizoxanide, tigecycline, vancomycin, tinidazole and metronidazole. Included in the isolates tested were 6 strains of the toxinotype III, NAP1/BI/027 group implicated in recent US, Canadian and European outbreaks. The most active agents in vitro were rifaximin, rifalazil, tizoxanide, nitazoxanide, and OPT-80 with MIC₅₀/MIC₉₀ (µg/ml) values of 0.0075/0.015, 0.0075/0.03, 0.06/0.125, 0.06/0.125, 0.125/0.125, respectively. However, three isolates demonstrated very high MICs to rifalazil and rifaximin (MIC >256 µg/ml). Ramoplanin, vancomycin, doripenem, and meropenem were also very active in vitro with narrow MIC₅₀/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.

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