Ceragenins are active against drug-resistant Candida auris clinical isolates in planktonic and biofilm forms.

BACKGROUND

Candida auris has emerged as a serious threat to human health. Of particular concern are the resistance profiles of many clinical isolates, with some being resistant to multiple classes of antifungals.

OBJECTIVES

Measure susceptibilities of C. auris isolates, in planktonic and biofilm forms, to ceragenins (CSAs). Determine the effectiveness of selected ceragenins in gel and cream formulations in eradicating fungal infections in tissue explants.

MATERIALS AND

METHODS

A collection of 100 C. auris isolates available at CDC was screened for susceptibility to a lead ceragenin. A smaller collection was used to characterize antifungal activities of other ceragenins against organisms in planktonic and biofilm forms. Effects of ceragenins on fungal cells and biofilms were observed via microscopy. An ex vivo model of mucosal fungal infection was used to evaluate formulated forms of lead ceragenins.

RESULTS

Lead ceragenins displayed activities comparable to those of known antifungal agents against C. auris isolates with MICs of 0.5-8 mg/L and minimum fungicidal concentrations (MFCs) of 2-64 mg/L. No cross-resistance with other antifungals was observed. Fungal cell morphology was altered in response to ceragenin treatment. Ceragenins exhibited activity against sessile organisms in biofilms. Gel and cream formulations including 2% CSA-44 or CSA-131 resulted in reductions of over 4 logs against established fungal infections in ex vivo mucosal tissues.

CONCLUSIONS

Ceragenins demonstrated activity against C. auris, suggesting that these compounds warrant further study to determine whether they can be used for topical applications to skin and mucosal tissues for treatment of infections with C. auris and other fungi.