In vitro activity of ibrexafungerp and comparators against Candida albicans genotypes from vaginal samples and blood cultures

Abstract

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 fluconazole