# In Vitro Activity of Rezafungin Against Planktonic and Biofilm Forms of Candida albicans and Nakaseomyces glabratus Clinical Isolates from Vascular Infections in Poland: A Pilot Study

## TL;DR

This study tests a new antifungal drug, rezafungin, against yeast infections in blood, showing it works well against drug-resistant strains and biofilms.

## Contribution

The study evaluates rezafungin's in vitro activity against biofilms of Candida albicans and Nakaseomyces glabratus from vascular infections.

## Key findings

- Rezafungin showed activity against all tested isolates with MIC50 = 0.016 and MIC90 = 0.25.
- Nakaseomyces glabratus isolates showed high susceptibility to rezafungin despite azole resistance.
- Rezafungin had reduced activity against biofilms compared to planktonic cells.

## Abstract

Background/Objectives: Certain yeast species are recognized as significant opportunistic pathogens, capable of causing severe systemic infections, particularly in immunocompromised individuals or those with disrupted physiological barriers. The rising incidence of invasive candidiasis associated with vascular infections poses a significant clinical challenge due to the high mortality rates and the limited efficacy of conventional antifungal therapies. The formation of resilient biofilms on vascular catheters by species such as Candida albicans and Nakaseomyces glabratus further complicates treatment, often leading to persistent fungemia and necessitating device removal. With the emergence of multidrug-resistant (MDR) strains, there is a critical need for new therapeutic agents like rezafungin—a novel, long-acting echinocandin with potential enhanced antibiofilm activity. Methods: This study tested susceptibility to antimycotics available in Poland (fluconazole, voriconazole, posaconazole, amphotericin B, anidulafungin, caspofungin, and micafungin) using the commercial Micronaut-AM test (Bruker, Bremen, Germany). Susceptibility to rezafungin (Angene Chemical, Great Britain) was determined using the microdilution method in RPMI medium, recommended by European Committee on Antimicrobial Susceptibility Testing (EUCAST), with amphotericin B as a control compound. We evaluated the biofilm-forming capacity and the in vitro activity of rezafungin against 42 clinical isolates of Candida albicans and Nakaseomyces glabratus recovered from positive blood cultures. Results: The obtained minimum inhibitory concentration (MIC) values suggest rezafungin activity against all the tested isolates, with different susceptibility to echinocandins and other antifungal drugs (azoles, amphotericin B) currently registered and used in Poland. The MIC readings for rezafungin were in the range of 0.008–0.5, with MIC50 = 0.016 and MIC90 = 0.25. The isolates were categorized as low, moderate, or strong biofilm producers according to established Stepanović criteria (cut-off values OD630 < 0.019, 0.19–0.38, >0.38, respectively). Furthermore, the higher minimum biofilm eradication concentrations (MBECs) compared to the minimum inhibitory concentrations (MICs) of planktonic cells confirm the reduced activity of rezafungin against biofilms. Conclusions: Critically, the high antibiofilm efficacy at clinically achievable concentrations suggests that rezafungin shows promise as a potential therapeutic option for catheter-related candidemia, though further clinical studies are needed. Furthermore, the high susceptibility of N. glabratus isolates—a species frequently associated with azole resistance—suggests rezafungin may be a valuable addition to the existing antifungal arsenal of multidrug-resistant (MDR) fungal infections in hospital settings. Future research should focus on in vivo models to confirm if these in vitro results translate into accelerated clearance of vascular biofilms.