Anidulafungin is a useful surrogate marker for predicting in vitro susceptibility to rezafungin among five Candida species using CLSI methods and interpretive criteria

TL;DR

This study shows that anidulafungin can reliably predict how Candida species respond to rezafungin, a new antifungal drug, using standard lab methods.

Contribution

Anidulafungin is identified as the best surrogate marker for predicting rezafungin susceptibility across five Candida species.

Findings

Anidulafungin showed 97.6% categorical agreement with rezafungin across Candida species.

Rezafungin nonsusceptibility correlated with FKS hotspot mutations in Candida isolates.

No surrogate works well for predicting rezafungin susceptibility in Candida dubliniensis.

Abstract

This study addresses the use of other echinocandins as surrogate markers to predict the susceptibility of rezafungin against the six most common Candida spp. The Clinical Laboratory Standards Institute (CLSI) reference broth microdilution method was performed to test 5,720 clinical isolates of six different Candida species. Species-specific interpretative criteria by CLSI breakpoints or epidemiological cutoff values were applied. Essential agreement was 100% within two doubling dilutions for all species and comparisons. The categorical agreement of rezafungin using anidulafungin against all Candida spp. was 97.6% (2.9% very major errors [VMEs], 0.2% major errors [MEs], and 2.2% minor errors [miEs]); for caspofungin, it was 99.6% (11.4% VME, 0.09% ME, and 0.19% miE); and for micafungin, it was 99.6% (14.3% VME, 0.15% ME, and 0.17% miE). There were species-specific differences that led to unacceptably high VME for Candida dubliniensis with all agents and for Candida parapsilosis when caspofungin or micafungin but not anidulafungin was used as the comparator. Genetic analysis showed rezafungin nonsusceptibility correlated well with FKS hotspot mutations. The best-performing surrogate was anidulafungin, which can be used to predict rezafungin susceptible or nonsusceptible in Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Candida krusei with low error rates and ≥90% essential and categorical agreement. Micafungin or caspofungin can also be used as a surrogate marker for predicting rezafungin susceptible or nonsusceptible in C. albicans, C. glabrata, C. tropicalis, and C. krusei. No surrogate performs appropriately to determine rezafungin susceptibility for C. dubliniensis.