Pan-resistant Candida auris isolates from the outbreak in New York are susceptible to ibrexafungerp (a glucan synthase inhibitor)

Zhu, Yan; Barat, Stephen; Borroto–Esoda, Katyna; Angulo, David; Chaturvedi, Sudha

doi:10.1016/j.ijantimicag.2020.105922

Cited by 29 publications

(19 citation statements)

References 12 publications

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“…Candida auris has been reported in over 39 countries as an important emerging fungal pathogen [48] with a high crude mortality rate and a propensity for multidrug resistance [53][54][55][56][57][58][59]. C. auris has also been reported as an important cause of nosocomial outbreaks [60,61] due to its ability to colonize skin, form biofilms and resist standard disinfectants; due to its ease of person-to-person and person-to-environment transmission [60][61][62].…”

Section: Important Pathogenic Fungi and Antifungal Spectrummentioning

confidence: 99%

Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor

Jallow

Govender

2021

JoF

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Ibrexafungerp (formerly SCY-078 or MK-3118) is a first-in-class triterpenoid antifungal or “fungerp” that inhibits biosynthesis of β-(1,3)-D-glucan in the fungal cell wall, a mechanism of action similar to that of echinocandins. Distinguishing characteristics of ibrexafungerp include oral bioavailability, a favourable safety profile, few drug–drug interactions, good tissue penetration, increased activity at low pH and activity against multi-drug resistant isolates including C. auris and C. glabrata. In vitro data has demonstrated broad and potent activity against Candida and Aspergillus species. Importantly, ibrexafungerp also has potent activity against azole-resistant isolates, including biofilm-forming Candida spp., and echinocandin-resistant isolates. It also has activity against the asci form of Pneumocystis spp., and other pathogenic fungi including some non-Candida yeasts and non-Aspergillus moulds. In vivo data have shown IBX to be effective for treatment of candidiasis and aspergillosis. Ibrexafungerp is effective for the treatment of acute vulvovaginal candidiasis in completed phase 3 clinical trials.

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Section: Important Pathogenic Fungi and Antifungal Spectrummentioning

confidence: 99%

Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor

Jallow

Govender

2021

JoF

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“…More than 150 strains with various resistance profile were screened and proved to be uniformly susceptible to SCY-078. In parallel, Chaturvedi et al reported that Ibrexafungerp was efficient against pan-resistant (defined as in vitro resistance to two or more azoles, all echinocandins and amphotericin B) C. auris isolates from the outbreak in New-York [98] and Ghannoum et al demonstrated that it was active to control skin infection and colonization of hospitalized patients [99]. Recently, a review compiled data on Ibrexafungerp, established it is a promising, new antifungal agent to treat C. auris infections, as patients experienced a complete response after treatment [100].…”

Section: In Vitro Screening and In Vivo Validationmentioning

confidence: 99%

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

et al. 2021

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Invasive fungal infections represent an expanding threat to public health. During the past decade, a paradigm shift of candidiasis from Candida albicans to non-albicans Candida species has fundamentally increased with the advent of Candida auris. C. auris was identified in 2009 and is now recognized as an emerging species of concern and underscores the urgent need for novel drug development strategies. In this review, we discuss the genomic epidemiology and the main virulence factors of C. auris. We also focus on the different new strategies and results obtained during the past decade in the field of antifungal design against this emerging C. auris pathogen yeast, based on a medicinal chemist point of view. Critical analyses of chemical features and physicochemical descriptors will be carried out along with the description of reported strategies.

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“…MICs for fluconazole were >256 μg/mL, 2 μg/mL for amphotericin B, and 2–16 μg/mL for echinocandins. From the same laboratory, an analysis of the susceptibility of five pan-resistant C. auris isolates, defined as in vitro resistance to more than two azoles, all echinocandins, and amphotericin B, reported MIC values to fluconazole (>256 μg/mL), amphotericin B (2 μg/mL), and echinocandins (ranging from 2 to >16 μg/mL) [ 15 ]. However, all these pan-resistant isolates exhibited MICs for ibrexafungerp ranging from 0.12 to 1 μg/mL, which were within the wild-type MIC range reported for C. auris .…”

Section: Ibrexafungerp For Candida Aurismentioning

confidence: 99%

“…An outbreak of infections due to C. auris was identified in New York healthcare facilities with high rates of mortality [ 13 ]. Since 2016, more than 1000 C. auris isolates were tested at the New York State Department of Health where rates of resistance were >99% with fluconazole, approximately 60% with amphotericin B, and >80% with voriconazole [ 14 , 15 ]. The in vitro efficacy of antifungal drug combinations was evaluated against these resistant C. auris isolates, where combinations of flucytosine with echinocandins or amphotericin B were most active [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Antifungal resistance with C. auris is acquired rather than intrinsic, and the primary mechanisms of resistance were characterized for echinocandins and azoles [ 8 ]. Multidrug-resistant and pan-resistant isolates of C. auris were also identified from clinical isolates [ 15 , 16 , 18 ]. Thus, a need exists for novel antifungal agents that demonstrate high levels of activity against C. auris and address these treatment gaps.…”

Section: Introductionmentioning

confidence: 99%

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Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections

et al. 2020

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Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC50 and MIC90) values in >400 C. auris isolates were 0.5 μg/mL and 1.0 μg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections.

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Pan-resistant Candida auris isolates from the outbreak in New York are susceptible to ibrexafungerp (a glucan synthase inhibitor)

Cited by 29 publications

References 12 publications

Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor

Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections

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