Antifungal activity of cephalosporins as an alternative for the combat of Candida auris.

Candida auris is a multidrug-resistant fungal pathogen that presents significant challenges in healthcare settings due to its robust biofilm-forming ability. Conventional antifungal treatments frequently prove ineffective, emphasizing the urgent need for innovative disinfection strategies, including the potential repurposing of existing agents. To evaluate the in vitro and in vivo antifungal and antibiofilm activity of cephalexin, cefixime, and cefotaxime against C. auris. The efficacy of cephalosporins was tested using in vitro assays for minimum inhibitory concentration (MIC), biofilm inhibition, biofilm eradication, cell membrane integrity, nucleotide leakage, sorbitol protection assay, and efflux pump inhibition. An in vivo model using Tenebrio molitor larvae assessed survival rates and fungal burden after treatment. Cephalexin, cefixime, and cefotaxime exhibited MICs of 64 mg/L against C. auris. Cephalosporins significantly inhibited biofilm formation, with cephalexin completely eradicating mature biofilms within 45 min, demonstrating superior activity compared to chlorhexidine. Cephalexin, cefixime, and cefotaxime do not cause damage to the fungal cell wall or interfere with C. auris efflux pumps. Instead, their activity triggers the externalization of nucleotides without promoting protein leakage. In T. molitor larvae, both cephalexin and cefixime significantly improved survival rates and reduced fungal burden, further supporting their therapeutic potential in managing C. auris infections. These findings highlight the potential of cephalexin and cefixime for repurposing as effective agents against superficial infections. Their demonstrated antibiofilm activity, biofilm eradication capabilities, and ability to reduce fungal burden in vivo underscore their promise in mitigating C. auris infections and enhancing infection control strategies.