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dc.contributor.authorCorbett, D.
dc.contributor.authorWise, A.
dc.contributor.authorBirchall, S.
dc.contributor.authorWarn, P.
dc.contributor.authorBaines, Simon D.
dc.contributor.authorCrowther, G.
dc.contributor.authorFreeman, J.
dc.contributor.authorChilton, C. H.
dc.contributor.authorVernon, J.
dc.contributor.authorWilcox, M. H.
dc.contributor.authorVickers, R. J.
dc.date.accessioned2017-09-01T15:07:41Z
dc.date.available2017-09-01T15:07:41Z
dc.date.issued2015-06-01
dc.identifier.citationCorbett , D , Wise , A , Birchall , S , Warn , P , Baines , S D , Crowther , G , Freeman , J , Chilton , C H , Vernon , J , Wilcox , M H & Vickers , R J 2015 , ' In vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficile ' , Journal of Antimicrobial Chemotherapy , vol. 70 , no. 6 , pp. 1751-1756 . https://doi.org/10.1093/jac/dkv006
dc.identifier.issn0305-7453
dc.identifier.urihttp://hdl.handle.net/2299/19278
dc.description© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.description.abstractOBJECTIVES: SMT19969 is a novel antimicrobial under clinical development for the treatment of Clostridium difficile infection (CDI). The objective was to determine the comparative susceptibility of 82 C. difficile clinical isolates (which included ribotype 027 isolates and isolates with reduced metronidazole susceptibility) to SMT19969, fidaxomicin, vancomycin and metronidazole and to determine the killing kinetics and post-antibiotic effects of SMT19969, fidaxomicin and vancomycin against C. difficile. METHODS: MICs were determined by agar incorporation. Killing kinetics and post-antibiotic effects were determined against C. difficile BI1, 630 and 5325 (ribotypes 027, 012 and 078, respectively). RESULTS: SMT19969 showed potent inhibition of C. difficile (MIC90=0.125 mg/L) and was markedly more active than either metronidazole (MIC90 = 8 mg/L) or vancomycin (MIC90 = 2 mg/L). There were no differences in susceptibility to SMT19969 between different ribotypes. Fidaxomicin was typically one doubling dilution more active than SMT19969 and both agents maintained activity against isolates with reduced susceptibility to metronidazole. In addition, SMT19969 was bactericidal against the C. difficile strains tested, with reductions in viable counts to below the limit of detection by 24 h post-inoculation. Vancomycin was bacteriostatic against all three strains. Fidaxomicin was bactericidal although reduced killing was observed at concentrations <20 × MIC against C. difficile BI1 (ribotype 027) compared with other strains tested. CONCLUSIONS: These data demonstrate that SMT19969 is associated with potent and bactericidal activity against the strains tested and support further investigation of SMT19969 as potential therapy for CDI.en
dc.format.extent6
dc.format.extent721673
dc.language.isoeng
dc.relation.ispartofJournal of Antimicrobial Chemotherapy
dc.subjectC. difficine
dc.subjectPAE
dc.subjectantimicrobial
dc.titleIn vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficileen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionMicrobiology and Biotechnology
dc.contributor.institutionBiosciences Research Group
dc.contributor.institutionCentre for Research in Mechanisms of Disease and Drug Discovery
dc.contributor.institutionDepartment of Clinical, Pharmaceutical and Biological Science
dc.contributor.institutionCentre for Future Societies Research
dc.description.statusPeer reviewed
rioxxterms.versionofrecord10.1093/jac/dkv006
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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