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.

Susceptibility to Clotrimazole of Candida spp. Isolated from the Genitourinary System—A Single Center Study

“…C. albicans and closely related species ( C. africana, C. dubliniensis ) are regarded as very sensitive to azoles, including clotrimazole. This rule was confirmed by several studies (including this article), in which MIC90 for these species ranged between 0.03 and 0.5 mg/L ( Table 3 ) [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 15 ].…”

In vitro activity of ibrexafungerp against Candida species isolated from blood cultures. Determination of wild-type populations using the EUCAST method

“…With the exception of J o u r n a l P r e -p r o o f the C. glabrata isolate harbouring a F659S mutation, the C. glabrata and C. tropicalis FKS mutant isolates show ibrexafungerp MICs falling within the wild type distribution, thus suggesting binding to different sites of the β-1,3-glucan synthase [3,5,7]. Likewise, ibrexafungerp in vitro activity is uniformly active against the non-wild type fluconazole isolate [6][7][8].…”

“…Ibrexafungerp is supposed to bind to β-1,3-glucan synthase but at a different site from that of echinocandins [3]. Ibrexafungerp has shown in vivo and in vitro activity against Candida spp, including some FKS-mutant echinocandin-resistant isolates [4][5][6][7] and fluconazole-resistant isolates [8].…”

Candidemia: Evolution of Drug Resistance and Novel Therapeutic Approaches

“…59 Moreover, ibrexafungerp is active against clinical isolates of Candida, including strains resistant to echinocandins and other antifungal agents. 60,61 Rezafungin is a novel echinocandin with an enhanced half-life and a long stability. These features enabled the administration once-weekly instead of the daily dose of the other echinocandins.…”