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Comparison of the efficacy of ramoplanin and vancomycin in both in vitro and in vivo models of clindamycin-induced Clostridium difficile infection.
J Antimicrob Chemother. 2005 Oct; 56(4):717-25.JA

Abstract

OBJECTIVES

Treatment of Clostridium difficile infection (CDI) is limited primarily to either metronidazole or vancomycin. We compared vancomycin and a novel glycolipodepsipeptide, ramoplanin, in both hamster and in vitro gut models of clindamycin-induced CDI.

METHODS

We used an in vitro triple-stage chemostat model that simulates the human gut, and an in vivo hamster model, both primed with clindamycin.

RESULTS

Clindamycin exposure elicited symptomatic disease in the hamster model, and promoted C. difficile germination and toxin production in the gut model. C. difficile germination and toxin production were not associated with depletion of gut microflora in the gut model, but were temporarily associated with subinhibitory concentrations of clindamycin. Both ramoplanin and vancomycin were associated with rapid symptom resolution in the hamster model, and rapid toxin titre decrease in the in vitro gut model. In both models of CDI, vancomycin was associated with greater persistence of C. difficile spores. C. difficile spores were recovered significantly more often from the caecal contents of vancomycin-treated (n = 19/23) compared with ramoplanin-treated (n = 6/23) hamsters (P < 0.05).

CONCLUSIONS

Results from the in vitro gut and hamster models were concordant. Ramoplanin and vancomycin were similarly effective at reducing cytotoxin production in the gut CDI model and in resolving symptoms in the hamster model. Ramoplanin may be more effective than vancomycin at killing spores and preventing spore recrudescence. These findings suggest a potential therapeutic role for ramoplanin in CDI that requires further clinical investigation.

Authors+Show Affiliations

Department of Microbiology, University of Leeds and The General Infirmary, Old Medical School, Leeds, LS1 3EX, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16143709

Citation

Freeman, Jane, et al. "Comparison of the Efficacy of Ramoplanin and Vancomycin in Both in Vitro and in Vivo Models of Clindamycin-induced Clostridium Difficile Infection." The Journal of Antimicrobial Chemotherapy, vol. 56, no. 4, 2005, pp. 717-25.
Freeman J, Baines SD, Jabes D, et al. Comparison of the efficacy of ramoplanin and vancomycin in both in vitro and in vivo models of clindamycin-induced Clostridium difficile infection. J Antimicrob Chemother. 2005;56(4):717-25.
Freeman, J., Baines, S. D., Jabes, D., & Wilcox, M. H. (2005). Comparison of the efficacy of ramoplanin and vancomycin in both in vitro and in vivo models of clindamycin-induced Clostridium difficile infection. The Journal of Antimicrobial Chemotherapy, 56(4), 717-25.
Freeman J, et al. Comparison of the Efficacy of Ramoplanin and Vancomycin in Both in Vitro and in Vivo Models of Clindamycin-induced Clostridium Difficile Infection. J Antimicrob Chemother. 2005;56(4):717-25. PubMed PMID: 16143709.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of the efficacy of ramoplanin and vancomycin in both in vitro and in vivo models of clindamycin-induced Clostridium difficile infection. AU - Freeman,Jane, AU - Baines,Simon D, AU - Jabes,Daniela, AU - Wilcox,Mark H, Y1 - 2005/09/05/ PY - 2005/9/7/pubmed PY - 2006/1/13/medline PY - 2005/9/7/entrez SP - 717 EP - 25 JF - The Journal of antimicrobial chemotherapy JO - J. Antimicrob. Chemother. VL - 56 IS - 4 N2 - OBJECTIVES: Treatment of Clostridium difficile infection (CDI) is limited primarily to either metronidazole or vancomycin. We compared vancomycin and a novel glycolipodepsipeptide, ramoplanin, in both hamster and in vitro gut models of clindamycin-induced CDI. METHODS: We used an in vitro triple-stage chemostat model that simulates the human gut, and an in vivo hamster model, both primed with clindamycin. RESULTS: Clindamycin exposure elicited symptomatic disease in the hamster model, and promoted C. difficile germination and toxin production in the gut model. C. difficile germination and toxin production were not associated with depletion of gut microflora in the gut model, but were temporarily associated with subinhibitory concentrations of clindamycin. Both ramoplanin and vancomycin were associated with rapid symptom resolution in the hamster model, and rapid toxin titre decrease in the in vitro gut model. In both models of CDI, vancomycin was associated with greater persistence of C. difficile spores. C. difficile spores were recovered significantly more often from the caecal contents of vancomycin-treated (n = 19/23) compared with ramoplanin-treated (n = 6/23) hamsters (P < 0.05). CONCLUSIONS: Results from the in vitro gut and hamster models were concordant. Ramoplanin and vancomycin were similarly effective at reducing cytotoxin production in the gut CDI model and in resolving symptoms in the hamster model. Ramoplanin may be more effective than vancomycin at killing spores and preventing spore recrudescence. These findings suggest a potential therapeutic role for ramoplanin in CDI that requires further clinical investigation. SN - 0305-7453 UR - https://www.unboundmedicine.com/medline/citation/16143709/Comparison_of_the_efficacy_of_ramoplanin_and_vancomycin_in_both_in_vitro_and_in_vivo_models_of_clindamycin_induced_Clostridium_difficile_infection_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dki321 DB - PRIME DP - Unbound Medicine ER -