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Ambush of Clostridium difficile spores by ramoplanin: activity in an in vitro model.
Antimicrob Agents Chemother. 2015 May; 59(5):2525-30.AA

Abstract

Clostridium difficile infection (CDI) is a gastrointestinal disease caused by C. difficile, a spore-forming bacterium that in its spore form is tolerant to standard antimicrobials. Ramoplanin is a glycolipodepsipeptide antibiotic that is active against C. difficile with MICs ranging from 0.25 to 0.50 μg/ml. The activity of ramoplanin against the spores of C. difficile 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. C. difficile spores were found to be stable in deionized water for 6 days. In vitro 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 C. difficile 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 C. difficile forms, supports further evaluation of ramoplanin for the prevention of relapse after C. difficile infection in patients.

Authors+Show Affiliations

Nanotherapeutics, Inc., Alachua, Florida, USA ckraus@nanotherapeutics.com.TechLab, Inc., Blacksburg, Virginia, USA.TechLab, Inc., Blacksburg, Virginia, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25691641

Citation

Kraus, Carl N., et al. "Ambush of Clostridium Difficile Spores By Ramoplanin: Activity in an in Vitro Model." Antimicrobial Agents and Chemotherapy, vol. 59, no. 5, 2015, pp. 2525-30.
Kraus CN, Lyerly MW, Carman RJ. Ambush of Clostridium difficile spores by ramoplanin: activity in an in vitro model. Antimicrob Agents Chemother. 2015;59(5):2525-30.
Kraus, C. N., Lyerly, M. W., & Carman, R. J. (2015). Ambush of Clostridium difficile spores by ramoplanin: activity in an in vitro model. Antimicrobial Agents and Chemotherapy, 59(5), 2525-30. https://doi.org/10.1128/AAC.04853-14
Kraus CN, Lyerly MW, Carman RJ. Ambush of Clostridium Difficile Spores By Ramoplanin: Activity in an in Vitro Model. Antimicrob Agents Chemother. 2015;59(5):2525-30. PubMed PMID: 25691641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ambush of Clostridium difficile spores by ramoplanin: activity in an in vitro model. AU - Kraus,Carl N, AU - Lyerly,Matthew W, AU - Carman,Robert J, Y1 - 2015/02/17/ PY - 2014/11/20/received PY - 2015/01/30/accepted PY - 2015/2/19/entrez PY - 2015/2/19/pubmed PY - 2016/1/12/medline SP - 2525 EP - 30 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 59 IS - 5 N2 - Clostridium difficile infection (CDI) is a gastrointestinal disease caused by C. difficile, a spore-forming bacterium that in its spore form is tolerant to standard antimicrobials. Ramoplanin is a glycolipodepsipeptide antibiotic that is active against C. difficile with MICs ranging from 0.25 to 0.50 μg/ml. The activity of ramoplanin against the spores of C. difficile 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. C. difficile spores were found to be stable in deionized water for 6 days. In vitro 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 C. difficile 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 C. difficile forms, supports further evaluation of ramoplanin for the prevention of relapse after C. difficile infection in patients. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/25691641/Ambush_of_Clostridium_difficile_spores_by_ramoplanin:_activity_in_an_in_vitro_model_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=25691641 DB - PRIME DP - Unbound Medicine ER -