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Antibiotics 2018, 7(1), 13; https://doi.org/10.3390/antibiotics7010013

Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model

1
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UK
2
School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK
*
Author to whom correspondence should be addressed.
Received: 31 December 2017 / Revised: 3 February 2018 / Accepted: 6 February 2018 / Published: 13 February 2018
(This article belongs to the Special Issue Bacteriophages: Alternatives to Antibiotics and Beyond)
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Abstract

Clostridium difficile infection (CDI) is a major cause of infectious diarrhea. Conventional antibiotics are not universally effective for all ribotypes, and can trigger dysbiosis, resistance and recurrent infection. Thus, novel therapeutics are needed to replace and/or supplement the current antibiotics. Here, we describe the activity of an optimised 4-phage cocktail to clear cultures of a clinical ribotype 014/020 strain in fermentation vessels spiked with combined fecal slurries from four healthy volunteers. After 5 h, we observed ~6-log reductions in C. difficile abundance in the prophylaxis regimen and complete C. difficile eradication after 24 h following prophylactic or remedial regimens. Viability assays revealed that commensal enterococci, bifidobacteria, lactobacilli, total anaerobes, and enterobacteria were not affected by either regimens, but a ~2-log increase in the enterobacteria, lactobacilli, and total anaerobe abundance was seen in the phage-only-treated vessel compared to other treatments. The impact of the phage treatments on components of the microbiota was further assayed using metagenomic analysis. Together, our data supports the therapeutic application of our optimised phage cocktail to treat CDI. Also, the increase in specific commensals observed in the phage-treated control could prevent further colonisation of C. difficile, and thus provide protection from infection being able to establish. View Full-Text
Keywords: Clostridium difficile; Clostridium difficile infection; bacteriophages; phage therapy; microbiome; in vitro fermentation model Clostridium difficile; Clostridium difficile infection; bacteriophages; phage therapy; microbiome; in vitro fermentation model
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Nale, J.Y.; Redgwell, T.A.; Millard, A.; Clokie, M.R.J. Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model. Antibiotics 2018, 7, 13.

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