Objectives: Emergence of azole resistance may contribute to recurrences of vulvovaginal candidiasis.
Thus, new drugs are needed to improve the therapeutic options. We studied the in vitro activity of
ibrexafungerp and comparators against Candida albicans isolates from vaginal samples and blood cultures.
Furthermore, isolates were genotyped to study compartmentalization of genotypes and the relationship
between genotype and antifungal susceptibility.
Methods: Candida albicans unique patient isolates (n ¼ 144) from patients with clinical suspicion of
vulvovaginal candidiasis (n ¼ 72 isolates) and from patients with candidaemia (n ¼ 72) were studied.
Antifungal susceptibility to amphotericin B, fluconazole, voriconazole, posaconazole, isavuconazole,
clotrimazole, miconazole, micafungin, anidulafungin and ibrexafungerp was tested (EUCAST 7.3.2).
Mutations in the erg11 gene were analysed and isolates genotyped.
Results: Ibrexafungerp showed high activity (MICs from 0.03 mg/L to 0.25 mg/L) against the isolates,
including those with reduced azole susceptibility, and regardless of their clinical source. Fluconazole
resistance rate was 7% (n ¼ 5/72) and 1.4% (n ¼ 1/72) in vaginal and blood isolates, respectively. Some
amino acid substitutions in the Erg11 protein were observed exclusively in phenotypically fluconazole
non-wild type. Population structure analysis suggested two genotype populations, one mostly involving
isolates from blood samples (66.3%) and the mostly from vaginal samples (69.8%). The latter group hosted
all fluconazole non-wild-type isolates.
Discussion: Ibrexafungerp shows good in vitro activity against Candida albicans from vaginal samples
including phenotypically fluconazole non-wild-type isolates. Furthermore, we found a certain population
structure where some genotypes show reduced susceptibility to fluconazol
