Auranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infection

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dc.contributor.authorAbutaleb, Nader S.en
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:17:16Zen
dc.date.available2020-09-21T16:17:16Zen
dc.date.issued2020-05-07en
dc.date.updated2020-09-21T16:17:14Zen
dc.description.abstractClostridioides difficile is the leading cause of nosocomial infections and a worldwide urgent public health threat. Without doubt, there is an urgent need for new effective anticlostridial agents due to the increasing incidence and severity of C. difficile infection (CDI). The aim of the present study is to investigate the in vivo efficacy of auranofin (rheumatoid arthritis FDA-approved drug) in a CDI mouse model and establish an adequate dosage for treatment. The effects of increased C. difficile inoculum, and pre-exposure to simulated gastric intestinal fluid (SGF) and simulated intestinal fluid (SIF), on the antibacterial activity of auranofin were investigated. Auranofin’s in vitro antibacterial activity was stable in the presence of high bacterial inoculum size compared to vancomycin and fidaxomicin. Moreover, it maintained its anti-C. difficile activity after being exposed to SGF and SIF. Upon testing in a CDI mouse model, auranofin at low clinically achievable doses (0.125 mg/kg and 0.25 mg/kg) significantly protected mice against CDI with 100% and 80% survival, respectively. Most importantly, auranofin (0.125 mg/kg and 0.25 mg/kg) significantly prevented CDI recurrence when compared with vancomycin. Collectively, these results indicate that auranofin could potentially provide an effective, safe and quick supplement to the current approaches for treating CDI.en
dc.description.versionPublished versionen
dc.format.extent8 page(s)en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier7701 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/s41598-020-64882-9en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.other10.1038/s41598-020-64882-9 (PII)en
dc.identifier.pmid32382070 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100042en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectTREATMENT FAILUREen
dc.subject1ST RECURRENCEen
dc.subjectMETRONIDAZOLEen
dc.subjectFIDAXOMICINen
dc.subjectEPIDEMIOLOGYen
dc.subjectPHARMACOLOGYen
dc.subjectEFFICACYen
dc.subjectDRUGen
dc.titleAuranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infectionen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2020-04-23en
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Techen

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