1076 - Activity of Rezafungin and Comparator Antifungal Agents Tested Against a Worldwide Collection of Contemporaneous Invasive Fungal Isolates (2019-2020)

Rezafungin (RZF) is a new echinocandin (ECH) with a long half-life and front-loaded drug exposure that allow for once-weekly intravenous administration. RZF is under Phase 3 development for the treatment of candidemia and invasive candidiasis and the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp. in blood and marrow transplant recipients. We evaluated the activity of RZF and comparators against invasive fungal isolates from the SENTRY Antimicrobial Surveillance Program.

Methods: A total of 1,427 Candida spp., 38 Cryptococcus neoformans (CNEO), 186 Aspergillus fumigatus (AFM), and 28 Aspergillus section Flavi (AFL) collected from 24 countries in 2019-2020 were tested. CLSI antifungal broth microdilution assays were performed according to standard method (M27, M38) with the exception that panels were made by dispensing 10 µL of a 20x drug stock solution into panels that contained 90 µL of RPMI and mixing. CLSI criteria were applied (M59, M60, M61).

Results: RZF demonstrated potent activity against C. albicans (CA; MIC_50/90, 0.03/0.06 mg/L), C. tropicalis (CT; MIC_50/90, 0.03/0.06 mg/L), C. glabrata (CG; MIC_50/90, 0.06/0.06 mg/L), C. krusei (CK; MIC_50/90, 0.03/0.03 mg/L), and C. dubliniensis (MIC_50/90, 0.06/0.12 mg/L). RZF inhibited 99.6% of C. parapsilosis (CP; MIC_50/90,1/2 mg/L) at ≤2 mg/L. RZF activity was similar to the other ECH against these 6 Candida spp. All CA, CT, and CK isolates as well as the majority of CG (96.2-97.9%) and CP (86.2-100%) isolates were susceptible (S) to comparator ECHs. Fluconazole resistance was detected among 0.5%, 4.5%, 10.5%, and 1.2% of CA, CG, CP, and CT, respectively. The azoles were active against CNEO, but all ECHs displayed limited activity against CNEO. ECHs were active against AFM (MEC₉₀ range, 0.015-0.06 mg/L) and AFL (MEC₉₀ range, 0.015-0.03 mg/L). RZF activity was similar to that of the other ECHs. All but 16 (8.6%) AFM isolates were S to voriconazole, and 100% of AFL were wild-type to mould-active azoles.

Conclusion:

RZF and other ECHs displayed similar activity against Candida and Aspergillus spp. isolates from invasive fungal infections. These in vitro results support the development of RZF for the treatment and prevention of invasive fungal disease.Table