Ambush of Clostridium difficile Spores by Ramoplanin: Activity in anIn VitroModel

Bibliographic Details
Authors and Corporations: Kraus, Carl N., Lyerly, Matthew W., Carman, Robert J.
Title: Ambush of Clostridium difficile Spores by Ramoplanin: Activity in anIn VitroModel
In: Antimicrobial Agents and Chemotherapy, 59, 2015, 5, p. 2525-2530
published:
American Society for Microbiology
Physical Description:2525-2530
ISSN/ISBN: 0066-4804
1098-6596
Summary:<jats:title>ABSTRACT</jats:title><jats:p><jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Clostridium difficile</jats:named-content>infection (CDI) is a gastrointestinal disease caused by<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">C. difficile</jats:named-content>, a spore-forming bacterium that in its spore form is tolerant to standard antimicrobials. Ramoplanin is a glycolipodepsipeptide antibiotic that is active against<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">C. difficile</jats:named-content>with MICs ranging from 0.25 to 0.50 μg/ml. The activity of ramoplanin against the spores of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">C. difficile</jats:named-content>has not been well characterized; such activity, however, may hold promise, since posttreatment residual intraluminal spores are likely elements of disease relapse, which can impact more than 20% of patients who are successfully treated.<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">C. difficile</jats:named-content>spores were found to be stable in deionized water for 6 days.<jats:italic>In vitro</jats:italic>spore counts were consistently below the level of detection for 28 days after even brief (30-min) exposure to ramoplanin at concentrations found in feces (300 μg/ml). In contrast, suppression of spore counts was not observed for metronidazole or vancomycin at human fecal concentrations during treatment (10 μg/ml and 500 μg/ml, respectively). Removal of the<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">C. difficile</jats:named-content>exosporium resulted in an increase in spore counts after exposure to 300 μg/ml of ramoplanin. Therefore, we propose that rather than being directly sporicidal, ramoplanin adheres to the exosporium for a prolonged period, during which time it is available to attack germinating cells. This action, in conjunction with its already established bactericidal activity against vegetative<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">C. difficile</jats:named-content>forms, supports further evaluation of ramoplanin for the prevention of relapse after<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">C. difficile</jats:named-content>infection in patients.</jats:p>
Type of Resource:E-Article
Source:American Society for Microbiology (CrossRef)
Language: English