2115. Activity of a Long-Acting Echinocandin Rezafungin and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates: SENTRY 2018

Abstract

BackgroundEchinocandins are the first-line treatment of candidemia. We evaluated the activity of rezafungin (RZF), a novel long-acting echinocandin with front-loaded drug exposure and extensive distribution to sites of infection, and comparators using CLSI broth microdilution methods against 709 invasive fungal isolates collected worldwide during 2018.MethodsSusceptibility (S) tests on 663 Candida spp. (6 species), 21 C. neoformans (CNEO), and 25 A. fumigatus (ASF) were conducted for RZF, anidulafungin (ANF), caspofungin (CSF), micafungin (MCF), and azoles. CLSI clinical breakpoint (CBP) and epidemiological cutoff value (ECV) interpretive criteria were applied. Isolates displaying echinocandin MIC>ECV were sequenced for fks hot spot (HS) mutations.ResultsRZF inhibited 99.7% of C. albicans (CA) isolates (MIC50/90, 0.015/0.06 mg/L), 100.0% of C. tropicalis (CT) (MIC50/90, 0.03/0.06 mg/L), 98.9% of C. glabrata (CG) (MIC50/90, 0.03/0.06 mg/L), 100.0% of C. krusei (CK) (MIC50/90, 0.015/0.12 mg/L), and 100.0% of C. dubliniensis (CD) (MIC50/90, 0.03/0.06 mg/L) at ≤0.12 mg/L. All (104/104 [100.0%]) C. parapsilosis (CP) isolates (MIC50/90,1/2 mg/L) were inhibited by RZF at ≤2 mg/L. Fluconazole resistance was detected among 9.0% of CG, 17.3% of CP, and 1.6% of CT. The activity of RZF against these 6 Candida spp. was similar to that of the other echinocandins, the vast majority of which were susceptible/wild type (WT) using CBP/ECV. A total of 5 isolates (3 CG, 1 CA, and 1 CT) displayed 1 or more non-WT or-resistant MIC values and were sequenced for fks HS mutations. Fluconazole and other azoles displayed good activity against CNEO whereas echinocandins including RZF displayed limited activity against CNEO isolates. Echinocandins displayed good activity against ASF, and RZF activity was similar to that of anidulafungin, caspofungin, and micafungin. All but 1 isolate (non-WT MIC for itraconazole, 2 mg/L) displayed WT MIC values for the mould-active azoles.ConclusionRezafungin was as active as other echinocandins against common organisms recovered from invasive fungal infections. These in vitro data contribute to accumulating research demonstrating rezafungin potential for prevention and treatment of invasive fungal infection. Disclosures All authors: No reported disclosures.