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Auranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infection.
Sci Rep. 2020 May 07; 10(1):7701.SR

Abstract

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.

Authors+Show Affiliations

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA.Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA. mseleem@purdue.edu. Purdue Institute of Inflammation, Immunology, and Infectious Disease, West Lafayette, IN, 47907, USA. mseleem@purdue.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32382070

Citation

Abutaleb, Nader S., and Mohamed N. Seleem. "Auranofin, at Clinically Achievable Dose, Protects Mice and Prevents Recurrence From Clostridioides Difficile Infection." Scientific Reports, vol. 10, no. 1, 2020, p. 7701.
Abutaleb NS, Seleem MN. Auranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infection. Sci Rep. 2020;10(1):7701.
Abutaleb, N. S., & Seleem, M. N. (2020). Auranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infection. Scientific Reports, 10(1), 7701. https://doi.org/10.1038/s41598-020-64882-9
Abutaleb NS, Seleem MN. Auranofin, at Clinically Achievable Dose, Protects Mice and Prevents Recurrence From Clostridioides Difficile Infection. Sci Rep. 2020 May 7;10(1):7701. PubMed PMID: 32382070.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Auranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infection. AU - Abutaleb,Nader S, AU - Seleem,Mohamed N, Y1 - 2020/05/07/ PY - 2020/01/10/received PY - 2020/04/23/accepted PY - 2020/5/9/entrez PY - 2020/5/10/pubmed PY - 2020/5/10/medline SP - 7701 EP - 7701 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - 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. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/32382070/Auranofin,_at_clinically_achievable_dose,_protects_mice_and_prevents_recurrence_from_Clostridioides_difficile_infection L2 - http://dx.doi.org/10.1038/s41598-020-64882-9 DB - PRIME DP - Unbound Medicine ER -
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