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Auranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infection
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Auranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infection
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Journal Article
Auranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infection
2020
Overview
Clostridioides 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/326
/ Animals
/ Anti-Bacterial Agents - pharmacology
/ Arthritis, Rheumatoid - drug therapy
/ Clostridioides difficile - drug effects
/ Clostridioides difficile - pathogenicity
/ Clostridium Infections - drug therapy
/ Clostridium Infections - microbiology
/ Clostridium Infections - pathology
/ Cross Infection - drug therapy
/ Cross Infection - microbiology
/ Dosage
/ Gastrointestinal Tract - drug effects
/ Gastrointestinal Tract - microbiology
/ Humanities and Social Sciences
/ Humans
/ Inoculum
/ Mice
/ Science
