P-1095. Activity of Rezafungin against Clinical Isolates of Uncommon Species of Candida spp

Abstract

Background

Rezafungin (RZF) is a long-acting echinocandin recently approved by the FDA to treat invasive candidiasis (IC) and candidemia. RZF CLSI breakpoints are available for Candida albicans, C. auris (CARS), C. dubliniensis (CDUB), C. glabrata, C. krusei, C. parapsilosis (CPRP), and C. tropicalis. However, RZF susceptibility results are scarce against other Candida spp. We evaluated in vitro activity of RZF, anidulafungin (AND), caspofungin (CAS), micafungin (MCF), fluconazole (FLC), voriconazole (VRC), and amphotericin B (AMB) against less common species of Candida spp. including CARS and CDUB.

Methods

We tested 590 (1/patient) less common Candida spp. isolates from IC infections as part of the SENTRY Program (Table 1). Isolates were collected from 2020-2022 in 80 hospitals including 31 in North America, 29 in Europe, 14 in Asia-Pacific, and 6 in Latin America. Isolates were identified by MALDI-TOF MS and/or sequencing and susceptibility testing was performed using the CLSI broth microdilution method. CLSI breakpoints or epidemiologic cutoff values were applied where available.

Results

RZF displayed similar activity to other echinocandins (within ±2-fold for MIC₅₀/₉₀ values) against all Candida spp. tested (Table 2). The lowest RZF MIC₅₀/₉₀ values were noted against C. kefyr (n=51, 0.03/0.06 mg/L) and C. pelliculosa (n=10, 0.015/0.03 mg/L). Higher RZF MIC_50/90 values were noted for C. guilliermondii (CGU, n=33, 1/1 mg/L) and for isolates in the CPRP complex (C. orthopsilosis (CORT) n=49, 0.5/1 mg/L, C. metapsilosis (CMET) n=25, 0.12/0.5 mg/L). The same pattern was seen with other echinocandins against these Candida spp. RZF was active against 97.7% of CDUB and 95.4% of CARS isolates applying the CLSI breakpoints. There were three CARS isolates that were resistant to RZF with MICs of 1- >4 mg/L. Two of these were susceptible to CAS and one was resistant or non-wildtype to all echinocandins. For FLC 69.7% of CGU, 85.7% of CORT, 100% CMET, and only 10.8% of CARS isolates were susceptible.

Conclusion

RZF has potent in vitro activity against a large collection of less common Candida spp. as demonstrated by worldwide surveillance testing. The activity of RZF against these isolates was comparable to other echinocandins and generally better than FLC.

Disclosures

Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for > 30 biotech and pharmaceutical companies: Grant/Research Support