University of Hertfordshire Research Archive

        JavaScript is disabled for your browser. Some features of this site may not work without it.

        Browse

        All of UHRABy Issue DateAuthorsTitlesThis CollectionBy Issue DateAuthorsTitles

        Arkivum Files

        My Downloads
        View Item 
        • UHRA Home
        • University of Hertfordshire
        • Research publications
        • View Item
        • UHRA Home
        • University of Hertfordshire
        • Research publications
        • View Item

        SMT19969 – a novel antibiotic for C. difficile : Clostridium difficile growth inhibition, spectrum of activity and resistance development

        Author
        Vickers, R.
        Tinsley, J.
        Storer, R.
        Wilson, F.
        Dorgan, C.
        Wren, S.
        Wilcox, M. H.
        Baines, Simon D.
        Freeman, J.
        Attention
        2299/14738
        Abstract
        Background: C.difficile infection (CDI) is now established as a major healthcare issue. However, therapy options are limited and recurrent disease remains a significant problem. SMT19969 is the lead compound from a novel class of narrow spectrum, GI restricted, antibiotics in preclinical development for the treatment of CDI. Methods: C. difficile minimum inhibitory concentrations (MIC) were determined by agar plate dilution on Wilkins Chalgren agar. MIC testing against gut flora bacteria was carried out using CSLI guidelines. Resistance development was evaluated by determining spontaneous mutation frequencies at 4x and 8x MIC and by serial passage over 14 days at sub-inhibitory (0.5 x MIC) drug concentrations. Results: SMT19969 showed potent C. difficile growth inhibition (MICs 0.06-0.25 mg/L; MIC90 = 0.125 mg/L) when tested against a panel of 82 clinical isolates comprised of 30 genotypically distinct strains, 31 isolates from ribotypes 027, 106 and 001 and 21 isolates with reduced susceptibility to metronidazole (MICs 4-8 mg/L). SMT19969 showed minimal growth inhibition against a panel of 100 isolates representing members of the gut flora. MIC90 values (mg/L) against each group were as follows: Bacteroides spp. >512; E. coli and other Proteobacteria > 512; Clostridium spp. other than C. difficile = 512; Lactobacillus spp. > 512; Eubacterium spp. = 512; Peptostreptococcus spp. = 128; Bifidobacterium spp. = 128.No drug resistant mutants were isolated. Spontaneous mutation frequencies using the C. difficile clinical isolates NCTC13366 and NCTC13307 were <3.17 x10-9 and <6.90 x10-9 respectively. No increase in SMT19969 MICs for C. difficile was seen despite 14 serial passages. Conclusions: The high activity and low rate of resistance development in C. difficile support the potential use of SMT19969 in the treatment of CDI. The extremely narrow spectrum of activity in gut bacteria testing offers the prospect of reduced risk of CDI recurrence due to flora inhibition
        Publication date
        2011-09
        Other links
        http://hdl.handle.net/2299/14738
        Metadata
        Show full item record
        Keep in touch

        © 2019 University of Hertfordshire

        I want to...

        • Apply for a course
        • Download a Prospectus
        • Find a job at the University
        • Make a complaint
        • Contact the Press Office

        Go to...

        • Accommodation booking
        • Your student record
        • Bayfordbury
        • KASPAR
        • UH Arts

        The small print

        • Terms of use
        • Privacy and cookies
        • Criminal Finances Act 2017
        • Modern Slavery Act 2015
        • Sitemap

        Find/Contact us

        • T: +44 (0)1707 284000
        • E: ask@herts.ac.uk
        • Where to find us
        • Parking
        • hr
        • qaa
        • stonewall
        • AMBA
        • ECU Race Charter
        • disability confident
        • AthenaSwan