Oral Administration of the Broad-Spectrum Antibiofilm Compound Toremifene Inhibits Candida albicans and Staphylococcus aureus Biofilm Formation In Vivo

Abstract

We here report on the in vitro activity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, including Candida albicans, Candida glabrata, Candida dubliniensis, Candida krusei, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. We validated the in vivo efficacy of orally administered toremifene against C. albicans and S. aureus biofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound.

Repurposing Toremifene for Treatment of Oral Bacterial Infections

“…Toremifene has been reported to have antibacterial activity against Francisella novicida, a model organism for the tularemia-causing pathogen Francisella tularensis; Staphylococcus aureus; Staphylococcus epidermidis; and Pseudomonas aeruginosa (22,23). Furthermore, we and others have reported on the antifungal effects of toremifene (23)(24)(25). In addition, toremifene has antiviral activity against Ebola virus (26).…”

“…Thanks to their potentially rapid bactericidal effects, activity against both growing and dormant populations, and low potential for resistance development, membraneacting agents are believed to be good candidates for treating biofilm-related persistent infections (28). Recently, the activity of toremifene against S. aureus biofilms formed under in vivo conditions has been described, further highlighting the potential of the compound to be used in treatment of biofilm-related bacterial infections (23). However, to evaluate the potential of toremifene for application against oral infections, additional experiments should be conducted using a relevant in vivo model (29).…”

Novel anti-infective implant substrates: Controlled release of antibiofilm compounds from mesoporous silica-containing macroporous titanium

“…A proofof-concept is established using toremifene as a broad-spectrum antibiofilm molecule. It has reported activity against the formation of biofilms of human pathogenic yeasts like Candida albicans [30,31] and bacterial pathogens like Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus [31] and Porphyromonas gingivalis (Jan Michiels, unpublished data), which was recently confirmed in vivo for C. albicans and S. aureus [31]. All these pathogenic species are known to form biofilms on medical devices and implants [32][33][34][35][36][37].…”

Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi, Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum

“…Geniş etki alanlı antibiyofilm bileşeni olan toremifenin kullanımının, Candida'lar tarafından biyofilm oluşumunu azalttığı gösterilmiştir. Bu durum, özellikle katetere bağlı tekrarlayan enfeksiyon gelişen hastalarda, Candida ve diğer biyofilm oluşan bakteri enfeksiyonlarının önlenmesinde önemli bir gelişmedir (16) .…”