Tags

Type your tag names separated by a space and hit enter

Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection.
J Antimicrob Chemother. 2013 Jan; 68(1):168-76.JA

Abstract

OBJECTIVES

First-line treatment options for Clostridium difficile infection (CDI) are limited. NVB302 is a novel type B lantibiotic under evaluation for the treatment of CDI. We compared the responses to NVB302 and vancomycin when used to treat simulated CDI in an in vitro gut model.

METHODS

We used ceftriaxone to elicit simulated CDI in an in vitro gut model primed with human faeces. Vancomycin and NVB302 were instilled into separate gut models and the indigenous gut microbiota and C. difficile total viable counts, spores and toxin levels were monitored throughout.

RESULTS

Ceftriaxone instillation promoted C. difficile germination and high-level toxin production. Commencement of NVB302 and vancomycin instillation reduced C. difficile total viable counts rapidly with only C. difficile spores remaining within 3 and 4 days, respectively. Cytotoxin was reduced to undetectable levels 5 and 7 days after vancomycin and NVB302 instillation commenced in vessel 2 and 3, respectively, and remained undetectable for the remainder of the experiments. C. difficile spores were unaffected by the presence of vancomycin or NVB302. NVB302 treatment was associated with faster resolution of Bacteroides fragilis group.

CONCLUSIONS

Both NVB302 and vancomycin were effective in treating simulated CDI in an in vitro gut model. C. difficile spore recrudescence was not observed following successful treatment with either NVB302 or vancomycin. NVB302 displayed non-inferiority to vancomycin in the treatment of simulated CDI, and had less deleterious effects against B. fragilis group. NVB302 warrants further clinical investigation as a potentially novel antimicrobial agent for the treatment of CDI.

Authors+Show Affiliations

Leeds Institute of Molecular Medicine, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.No affiliation info availableNo affiliation info availableNo 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

22966180

Citation

Crowther, Grace S., et al. "Evaluation of NVB302 Versus Vancomycin Activity in an in Vitro Human Gut Model of Clostridium Difficile Infection." The Journal of Antimicrobial Chemotherapy, vol. 68, no. 1, 2013, pp. 168-76.
Crowther GS, Baines SD, Todhunter SL, et al. Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection. J Antimicrob Chemother. 2013;68(1):168-76.
Crowther, G. S., Baines, S. D., Todhunter, S. L., Freeman, J., Chilton, C. H., & Wilcox, M. H. (2013). Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection. The Journal of Antimicrobial Chemotherapy, 68(1), 168-76. https://doi.org/10.1093/jac/dks359
Crowther GS, et al. Evaluation of NVB302 Versus Vancomycin Activity in an in Vitro Human Gut Model of Clostridium Difficile Infection. J Antimicrob Chemother. 2013;68(1):168-76. PubMed PMID: 22966180.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection. AU - Crowther,Grace S, AU - Baines,Simon D, AU - Todhunter,Sharie L, AU - Freeman,Jane, AU - Chilton,Caroline H, AU - Wilcox,Mark H, Y1 - 2012/09/10/ PY - 2012/9/12/entrez PY - 2012/9/12/pubmed PY - 2013/9/24/medline SP - 168 EP - 76 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 68 IS - 1 N2 - OBJECTIVES: First-line treatment options for Clostridium difficile infection (CDI) are limited. NVB302 is a novel type B lantibiotic under evaluation for the treatment of CDI. We compared the responses to NVB302 and vancomycin when used to treat simulated CDI in an in vitro gut model. METHODS: We used ceftriaxone to elicit simulated CDI in an in vitro gut model primed with human faeces. Vancomycin and NVB302 were instilled into separate gut models and the indigenous gut microbiota and C. difficile total viable counts, spores and toxin levels were monitored throughout. RESULTS: Ceftriaxone instillation promoted C. difficile germination and high-level toxin production. Commencement of NVB302 and vancomycin instillation reduced C. difficile total viable counts rapidly with only C. difficile spores remaining within 3 and 4 days, respectively. Cytotoxin was reduced to undetectable levels 5 and 7 days after vancomycin and NVB302 instillation commenced in vessel 2 and 3, respectively, and remained undetectable for the remainder of the experiments. C. difficile spores were unaffected by the presence of vancomycin or NVB302. NVB302 treatment was associated with faster resolution of Bacteroides fragilis group. CONCLUSIONS: Both NVB302 and vancomycin were effective in treating simulated CDI in an in vitro gut model. C. difficile spore recrudescence was not observed following successful treatment with either NVB302 or vancomycin. NVB302 displayed non-inferiority to vancomycin in the treatment of simulated CDI, and had less deleterious effects against B. fragilis group. NVB302 warrants further clinical investigation as a potentially novel antimicrobial agent for the treatment of CDI. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/22966180/Evaluation_of_NVB302_versus_vancomycin_activity_in_an_in_vitro_human_gut_model_of_Clostridium_difficile_infection_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dks359 DB - PRIME DP - Unbound Medicine ER -