gms | German Medical Science

Objectives: The Center for Disease Control (CDC) issued an urgent threat level warning regarding Candida auris multi-drug resistant (MDR) yeast strains causing severe infections with high transmission rates. The aim of this study was to test the impact of antifungals loaded into a calcium sulfate antibiotic carrier on three strains of MDR C. auris.

Methods: C. auris strains NCPF 8971, NCPF 8977 and NCPF 8984 were obtained from the National Collection of Pathogenic Fungi. Calcium sulfate (Stimulan Rapid Cure, Bicomposites, Keele, UK) was loaded with 200 mg fluconazole, 70 mg caspofungin or 100 mg of amphotericin B per 10CC and moulded into 6 mm beads. One bead was placed onto a lawn of each strain in triplicate and the zone of inhibition (ZOI) was measured after 3 days. To determine the minimum inhibitory concentration (MIC) serial dilutions of each antifungal were added to the three C. auris strains in a 96-well microtiter plate in triplicate. Following 24 hours incubation recovery was performed using spot plating.

Results and conclusion: Strain NCPF 8971 was sensitive to caspofungin released from the calcium sulfate bead (CSB) with a ZOI of 28 mm, but no zones were observed with amphotericin B or fluconazole. NCPF 8977 was sensitive to caspofungin and amphotericin B released from the CSB with ZOI’s of 29 mm and 10 mm, respectively, but was resistant to fluconazole. Similarly, for NCPF 8984 a ZOI was observed for caspofungin (33 mm) and amphotericin B (8 mm) but not fluconazole. The MIC was determined to be above 500 µg/mL and 250 µg/mL for all strains for fluconazole and caspofungin respectively. For amphotericin B NCPF 8971 and NCPF 8977 had an MIC of 31.25 µg/mL and NCPF 8984 an MIC of 7.80 µg/mL.

CDC lists the tentative breakpoints for caspofungin, fluconazole and amphotericin B as 2, 32 and 2 µg/mL respectively, above which strains are considered resistant. Therefore, the MIC assay showed all strains were highly resistant to caspofungin and fluconazole and resistant to amphotericin B. Despite this resistance, a ZOI was achieved for caspofungin with all three strains and amphotericin B for two strains.

This data shows antifungals released from CSBs can be effective against MDR C. auris in vitro, even where no MIC can be established because of high antifungal resistance. We propose this is because CSB’s can release antifungals at very high concentrations for sustained periods of time. This in vitro data suggests that antifungals loaded into CSBs are a potential treatment option in C. auris infections.