Abstract

Abstract Background Rezafungin (RZF) is a new echinocandin (ECH) approved by the US FDA to treat candidemia and invasive candidiasis (IC). Fluconazole (FLC) resistance (R) is a raising concern to treat IC, and ECHs are often used as first-line therapy. We evaluated the in vitro activity of RZF, caspofungin (CSF), micafungin (MCF), anidulafungin (ANF), and azoles against a global collection of 500 Candida isolates causing IC. Methods C. albicans (CA; 233 isolates; 46.6%), C. glabrata (CG; 102; 20.4%), C. parapsilosis (CP; 82; 16.4%), C. tropicalis (CT; 41; 8.2%), C. krusei (CK; 18; 3.6%), C. dubliniensis (CD; 15; 3.0%), and C. auris (CARS; 9; 1.8%) isolates were collected (1/patient) in 2022 from 52 medical centers located in Europe (EU; n=203; 19 centers), North America (NA; n=167; 14 centers), Asia-Pacific (AP; n=63; 8 centers), and Latin America (LA, n=67; 7 centers), identified by MALDI-TOF MS and/or sequencing and tested by CLSI broth microdilution. CLSI breakpoints (BP) were applied where available. CARS CDC tentative BPs were applied. Results RFZ exhibited activity against CA (Table) inhibiting 99.1% of the isolates overall, and 98.6%, 99.0%, 100%, and 100% of isolates from NA, EU, AP, and LA. Only 1 CA isolate (from US) displayed a FLC MIC value within the susceptible-dose dependent (SDD) category. CSP, ANF, and MCF showed S rates of 99.1% against CA. All but 1 CG isolate was susceptible (S) to RZF (99.0%S). CG S rates to CSP, ANF, MCF, and FLC were 98.0%, 98.0%, 97.1%, and 96.1% (SDD), respectively. All CP isolates were S to RZF, CSF, and MCF. However, only 84.1% of CP isolates were S to FLC. RZF and other ECHs inhibited all FLC-R isolates (10 total, 9 EU and 1 US). All CT and CK isolates were S to RZF and other ECHs. All CT were also S to azoles, and 94.4% of CK were S to VRC. Only RZF BPs are available by CLSI against CD (86.7%S). All CARS isolates (9 total; 4 EU, 3 NA, and 2 LA) were FLC-R; but 77.8% and 88.9% were S to RZF and other ECHs, respectively. Conclusion RZF demonstrated potent in vitro activity against invasive candidiasis isolates regardless of the region, and remained active against FLC-R CP and most of the FLC-R CARS isolates. Based on MIC50 and MIC90 results, RZF had similar activity to the other ECHs overall. Disclosures Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), bioMerieux: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Abby Klauer, BS, Melinta: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support

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