Abstract
Multidrug-resistant enterococcal pathogens, especially vancomycin-resistant enterococci (VRE), are among the pathogens that require new antibiotic innovation. The colonization of the gut represents a major pathway by which VRE can cause infection and spread to other patients. In the current study, auranofin (FDA-approved rheumatoid arthritis drug) is evaluated for its potential use as a decolonizing agent for VRE. Auranofin was found to exert potent antimicrobial activity against a wide range of enterococcal clinical isolates with a minimum inhibitory concentration of 1 μg/mL. No resistant mutants could be developed against auranofin over the course of 14 passages. Auranofin was also found to exert potent anti-biofilm activity against VRE. Auranofin was superior to linezolid, the drug of choice for VRE infection treatment, in the in vivo mouse model. Auranofin significantly reduced the VRE burden in feces, cecum, and ileum contents after 8 days of treatment. Accordingly, this study provides valuable evidence that auranofin has significant promise as a novel gastrointestinal decolonizing agent for VRE.
Highlights
Enterococcal species are one of the major pathogens of healthcare settings[1]
Enterococci, especially E. faecium, exhibits intrinsic resistance against several classes of antibiotics and can develop resistance via mutation or exogenous gene transfer, which resulted in the emergence of multi-drug resistant enterococcal strains
We tested the activity of auranofin against a wide panel of enterococcal isolates and compared auranofin to the control antibiotics
Summary
Enterococcal species are one of the major pathogens of healthcare settings[1]. Two strains, Enterococcus faecium and Enterococcus faecalis, are of major concern. Vancomycin-resistant enterococcal (VRE) infections comprise most Enterococcus faecium infections as well as a significant proportion of Enterococcus faecalis infections[1]. No drugs are approved by the Food and Drug Administration (FDA) to decolonize VRE from the intestine. Auranofin is an FDA-approved drug for the treatment of rheumatoid arthritis, it has a well-studied safety profile[11]. Adverse effects associated with auranofin administration are rare and mostly associated with long-term use These adverse reactions include diarrhea (2–5% of the patients), skin rash, and extremely rare thrombocytopenia. Even though auranofin is oral bioavailable FDA-approved drug, only 20–30% of the oral dose is being absorbed[17]. Auranofin is being evaluated for its ability to decolonize VRE in the GI tract
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