In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) Against Contemporary Blood Isolates From Medically Relevant Species of Candida: A European Study

Abstract

BackgroundIbrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis.ObjectiveThe aim of this study was to assess the in vitro activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of Candida.MethodsIbrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163 Candida albicans, 108 Candida parapsilosis, 60 Candida glabrata, 40 Candida tropicalis, 29 Candida krusei, 20 Candida orthopsilosis, 6 Candida guilliermondii, 2 Candida famata, 2 Candida lusitaniae, and 1 isolate each of Candida bracarensis, Candida catenulata, Candida dubliniensis, and Candida kefyr. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22 Candida auris from different clinical specimens were evaluated.ResultsIbrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for C. albicans (geometric MIC 0.062 mg/L, MIC range 0.016–0.5 mg/L) and the highest ibrexafungerp MICs were observed for C. tropicalis (geometric MIC 0.517 mg/L, MIC range 0.06–≥8 mg/L). Modal MICs/MIC50s (mg/L) against Candida spp. were 0.125/0.06 for C. albicans, 0.5/0.5 for C. parapsilosis, 0.25/0.25 for C. glabrata, 0.5/0.5 for C. tropicalis, 1/1 for C. krusei, 4/2 for C. orthopsilosis, and 0.5/0.5 for C. auris. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%) C. parapsilosis, 4 (5%) C. glabrata, and 1 (2.5%) C. tropicalis.ConclusionIbrexafungerp showed a potent in vitro activity against Candida.

EUCAST Ibrexafungerp MICs and Wild-Type Upper Limits for Contemporary Danish Yeast Isolates

“…This suggests a stable and robust intra-laboratory performance of the EUCAST method. The modal MICs obtained in this study were identical to or one dilution from the modal MIC both for the two QC strains also repeatedly tested by Mesquida et al [ 12 ], and for the common Candida species included in recent single and multicentre studies of ibrexafungerp EUCAST susceptibility [ 12 , 13 , 14 ]. These observations suggest a good inter-laboratory agreement.…”

“…Next, the ibrexafungerp MIC distributions were compared to those from three recent publications ( Table 3 ) [ 12 , 13 , 14 ]. All MIC distributions were unimodal with the exception of a bimodal MIC distribution for C. albicans (modes 0.03 and 0.125 mg/L) reported in the multicentre study by Quindos et al [ 14 ], and which therefore was excluded from the WT-UL determination for the aggregated data. The species-specific modal MICs all fell within ± 1 two-fold dilution from the most common species-specific modal MIC.…”

“…These observations suggest a good inter-laboratory agreement. Of note however, a bimodal MIC distribution was noted in the multicentre study for C. albicans specifically, with a first peak at 0.03 mg/L and another at 0.125 mg/L suggesting that some optimisation may be warranted, which will be facilitated once QC MIC target and ranges have been established [ 14 ].…”

“…To encompass this variation, EUCAST requires at least 100 MICs from at least five independent sources, each consisting of at least 15 isolates and for which the modal MIC may not deviate more than one two-fold dilution from the most common mode for dataset used for EUCAST ECOFF setting [ 8 ]. So far, three studies have reported single or multicentre MICs [ 12 , 13 , 14 ]. The objectives of this study were to examine the in vitro activity of ibrexafungerp against a nationwide and representative sample of contemporary clinical yeast isolates of Candida , to compare the MICs obtained with those recently reported and set preliminary wild-type upper limits (WT-UL), and to compare the activity of ibrexafungerp to that of other agents licensed for the therapy of candidiasis.…”

Postantifungal Effect of Antifungal Drugs against Candida: What Do We Know and How Can We Apply This Knowledge in the Clinical Setting?

“…Ibrexafungerp is the first triterpenoid class antifungal agent labeled for the treatment of vulvovaginitis [ 111 ]. Although it has been shown that ibrexafungerp displays potent in vitro and in vivo activity against the most clinically relevant species of Candida [ 112 ], so far, no PAFE studies have been published for this new drug. This semi-synthetic derivative of the terpenoid enfumafungin, acts by inhibiting glucan synthase, decreasing 1,3-β-D-glucan polymers and weakening fungal cell wall [ 113 ].…”