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Repurposing Agents as Anti-Infective Therapeutics to Aid in the Treatment of Candida auris Infections
Nazary Nebeluk1,2, James B Doub1,2
1The Doub Laboratory of Translational Bacterial Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Background:
Candida auris is an emerging nosocomial fungal pathogen whose inherent multidrug resistance and ability to form biofilms make treatment extremely difficult. Given the limited number of therapeutic options available and the poor clinical outcomes associated with current therapeutics, this study evaluated the potential of repurposing existing agents to treat C. auris infections.
Methods:
Six clinical C. auris isolates from a single tertiary care center were tested for in vitro susceptibility to topical agents (hypochlorous acid, chlorhexidine gluconate, sodium hypochlorite) and systemic agents (N-acetylcysteine, ethylenediaminetetraacetic acid, ethyl pyruvate). Furthermore, these six isolates were allowed to form biofilms and the ability of repurposed agents to disrupt C. auris biofilms was measured.
Results:
All agents except N-acetylcysteine demonstrated inhibitory activity against planktonic C. auris. With respect to C. auris biofilms, these were characterized using electron microscopy and all six agents showed statistically significant (p < 0.05) ability to disrupt biofilms over controls. Moreover, the ability to disrupt biofilms was also statistically significant (p < 0.05) when compared to use of either normal saline or amphotericin B.
Discussion:
These findings support the potential clinical utility of repurposing existing agents, such as Ethyl Pyruvate or EDTA, for systemic C. auris infections, or hypochlorous acid for C. auris wound infections. Yet, further studies are needed to optimize dosing parameters and evaluate in vivo efficacy and tolerability.
Insights
Repurposing existing agents like Ethyl Pyruvate or hypochlorous acid shows promise for treating multidrug-resistant Candida auris infections. These agents effectively inhibited planktonic growth and disrupted biofilms, offering new therapeutic avenues.
Area of Science:
- Mycology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- *Candida auris* is a challenging nosocomial pathogen due to multidrug resistance and biofilm formation.
- Limited therapeutic options and poor outcomes necessitate novel treatment strategies.
- This study explores repurposing existing agents against *C. auris*.
Purpose of the Study:
- To evaluate the efficacy of repurposed topical and systemic agents against *Candida auris*.
- To assess the ability of these agents to disrupt established *C. auris* biofilms.
- To identify potential new treatments for *C. auris* infections.
Main Methods:
- In vitro susceptibility testing of six clinical *C. auris* isolates against topical (hypochlorous acid, chlorhexidine gluconate, sodium hypochlorite) and systemic (N-acetylcysteine, ethylenediaminetetraacetic acid, ethyl pyruvate) agents.
- Biofilm disruption assays were performed using the six agents.
- Electron microscopy was used to characterize biofilms.
Main Results:
- All agents except N-acetylcysteine inhibited planktonic *C. auris* growth.
- All six agents demonstrated statistically significant disruption of *C. auris* biofilms compared to controls.
- Biofilm disruption was significantly greater than with normal saline or amphotericin B.
Conclusions:
- Ethyl Pyruvate, EDTA, and hypochlorous acid show potential for treating systemic and wound *C. auris* infections, respectively.
- Repurposing these agents offers a promising strategy against difficult-to-treat *C. auris*.
- Further in vivo studies are required to confirm efficacy and safety.
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