P-1196. Geographic distribution, MIC testing, and susceptibility rates of Candida auris isolates collected in the United States since 2014

TL;DR

This study examines the spread and drug resistance patterns of Candida auris in the US, highlighting rezafungin as a promising treatment option.

Contribution

The study provides new insights into the geographic distribution and susceptibility patterns of Candida auris isolates in the US.

Findings

Candida auris isolates showed high resistance to fluconazole and amphotericin B.

Rezafungin (RZF) susceptibility was high, with minimal cross-resistance observed.

Isolates not susceptible to rezafungin had FKS1 gene alterations.

Abstract

Candida auris (CARS) is an emerging infectious threat due to rising infection rates, eradication difficulty, and multidrug resistance. The US Centers for Disease Control (CDC) has tentative resistant (R)-only breakpoints (BP) against CARS for fluconazole (FLC), amphotericin B (AmB), anidulafungin (AND), caspofungin (CAS), and micafungin (MCF) with the caveat that the correlation between the values and clinical outcomes is unknown. Susceptible (S)-only BP for CARS from the Clinical and Laboratory Standards Institute (CLSI) exist for rezafungin (RZF). The CLSI S-only BP for RZF is several dilutions lower than the R CDC BPs for other echinocandins (ECH). It is imperative to understand the geographic distribution of CARS and MIC patterns to RZF and other agents.

CARS clinical isolates were collected from invasive candidal infections between 2014 – 2024 in 12 hospitals in 5 US Census divisions. Antifungal susceptibility testing was performed by reference broth microdilution with interpretation for AND, CAS, MCF, FLC, and AmB by CDC criteria (R ≥4, ≥2, ≥4, ≥32, and ≥2 mg/L) and RZF by CLSI criteria (NS≥1 mg/L). Isolates R/NS to any ECH were submitted to whole genome sequencing and analyzed for alterations in FKS1.

79 isolates were tested. Exponential increase in numbers is seen since 2021 (Figure 1). 86.1% were S to RZF; 97.5% and 44.3% were R to FLC and AmB, respectively. 77 isolates were R to FLC, within this group, 85.7% were S to RZF (Table 1). 35 isolates were R to AmB, these were all R to FLC and 88.6% were S to RZF. No RZF NS isolates were collected prior to 2022, there were 2 isolates in 2022, 4 in 2023, and 5 in 2024 (11 total). Isolates that were only NS to RZF were wildtype (WT) for FKS1 whereas those R/NS to ≥ 1 ECH had FKS1 alterations (Table 1).

CARS isolates have been rapidly increasing in prevalence-based surveillance. For ECH, molecular analysis indicates that isolates with an in vitro susceptibility profile showing NS to RZF but not-R to other ECH are WT for FKS1. RZF is an empiric treatment of choice for CARS given high R rates to FLC and AmB, minimal cross-resistance, and lack of S breakpoints for other ECH.

Marisa Winkler, MD, PhD, Basilea: Advisor/Consultant|Basilea: Grant/Research Support|GSK: Advisor/Consultant|GSK: Grant/Research Support|Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support Kelley A. Fedler, BS, Melinta Therapeutics: Grant/Research Support Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support

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