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

Mesquida, Aina; Díaz-García, Judith; Sánchez‐Carrillo, Carlos; Muñóz, Patricia; Escribano, Pilar; Guinea, Jesús

doi:10.1016/j.cmi.2021.09.030

Cited by 20 publications

(22 citation statements)

References 14 publications

(17 reference statements)

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“…In both studies, ibrexafungerp displayed remarkably lower MICs than micafungin against C. parapsilosis . Although Mesquida et al. (2022) did not differentiate among C. parapsilosis species complex, they also reported lower MICs for ibrexafungerp than for echinocandins.…”

Section: Discussionmentioning

confidence: 82%

“…Although there are no clinical breakpoints (CBPs) or ECVs available for ibrexafungerp, the study by Mesquida et al. (2022) as well as the present work have proposed WTULs.…”

Section: Discussionmentioning

confidence: 86%

“…(2022) did not differentiate among C. parapsilosis species complex, they also reported lower MICs for ibrexafungerp than for echinocandins. These high MIC values reported for echinocandins against C. parapsilosis have been associated with substitutions in the hs1 region of FKS1 ( Garcia-Effron et al., 2008 ; Dudiuk et al., 2017 ; Marcos-Zambrano et al., 2017 ; Mesquida et al., 2022 ). Schell et al.…”

Section: Discussionmentioning

confidence: 94%

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

Quindós

Miranda-Cadena

San-Millán

et al. 2022

Front. Cell. Infect. Microbiol.

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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.

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Section: Discussionmentioning

confidence: 82%

“…Although there are no clinical breakpoints (CBPs) or ECVs available for ibrexafungerp, the study by Mesquida et al. (2022) as well as the present work have proposed WTULs.…”

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 94%

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

Quindós

Miranda-Cadena

San-Millán

et al. 2022

Front. Cell. Infect. Microbiol.

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“…The triterpenoid ibrexafungerp, a new class of glucan synthase inhibitor currently being evaluated in various phase III trials, has shown excellent bioavailability after oral intake [ 43 ]; this drug may eventually be a good alternative when the use of azoles or echinocandins is contraindicated for any reason. We found that all isolates here tested, including those showing resistance to fluconazole and/or echinocandins, were considered ibrexafungerp wild type, which is in line with the high activity of this drug against isolates from blood and other clinical sources [ 27 ]. Clonal outbreaks of fluconazole-resistant C. parapsilosis isolates have been reported in different hospitals [ 44 ].…”

Section: Discussionmentioning

confidence: 84%

“…Isolates were categorized as resistant, susceptible, wild type, or non-wild-type according to clinical breakpoints or tentative epidemiological cutoff values (ECOFFs) provided by EUCAST [ 25 ]. Since there are no available clinical breakpoints for isavuconazole and ibrexafungerp, we used previously proposed tentative ECOFFs or wild-type upper limits [ 26 , 27 ]. All C. krusei isolates were considered intrinsically resistant to fluconazole.…”

Section: Methodsmentioning

confidence: 99%

Incidence of Candidemia Is Higher in COVID-19 versus Non-COVID-19 Patients, but Not Driven by Intrahospital Transmission

Machado

Estévez

Sánchez‐Carrillo

et al. 2022

JoF

Self Cite

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There is scarce information on the actual incidence of candidemia in COVID-19 patients. In addition, comparative studies of candidemia episodes in COVID-19 and non-COVID-19 patients are heterogeneous. Here, we assessed the real incidence, epidemiology, and etiology of candidemia in COVID-19 patients, and compared them with those without COVID-19 (2020 vs. 2019 and 2020, respectively). We also genotyped all C. albicans, C. parapsilosis, and C. tropicalis isolates (n = 88), causing candidemia in both groups, providing for the first time a genotypic characterization of isolates gathered in patients with either COVID-19 or non-COVID-19. Incidence of candidemia was higher in patients with COVID-19 than non-COVID-19 (4.73 vs. 0.85 per 1000 admissions; 3.22 vs. 1.14 per 10,000 days of stay). No substantial intergroup differences were found, including mortality. Genotyping proved the presence of a low number of patients involved in clusters, allowing us to rule out rampant patient-to-patient Candida transmission. The four patients, involved in two clusters, had catheter-related candidemia diagnosed in the first COVID-19 wave, which demonstrates breaches in catheter management policies occurring in such an overwhelming situation. In conclusion, the incidence of candidemia in patients with COVID-19 is significantly higher than in those without COVID-19. However, genotyping shows that this increase is not due to uncontrolled intrahospital transmission.

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Management of invasive candidiasis: A focus on rezafungin, ibrexafungerp, and fosmanogepix

August,

Kale‐Pradhan

2024

Pharmacotherapy

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Management of invasive fungal infections is challenging with growing antifungal resistance. Broad antifungal use has resulted in greater intrinsic and acquired resistance among Candida spp. It is important for clinicians to recognize the relationship between host susceptibility, site of infection, Candida resistance profiles, specific drug pharmacokinetics and pharmacodynamics, and the role of novel antifungal agents. This narrative review covers the role of rezafungin, ibrexafungerp, and fosmanogepix in the management of invasive candidiasis (IC). The PubMed Database, Embase, and ClinicalTrials.gov were searched between January 2006 and January 2024 using the following terms: rezafungin, CD101, ibrexafungerp, SCY‐078, fosmanogepix, APX001, candidemia, and invasive candidiasis. Review articles, prospective clinical trials, and observational studies published in the English language were reviewed. Studies evaluating pharmacology, pharmacokinetics, efficacy, and safety in animals and humans were also reviewed. Promising data continues to emerge in support of novel drug therapies for IC and candidemia. Rezafungin possesses a unique pharmacodynamic profile that might be advantageous compared to other echinocandins, with a practical, once‐weekly dosing interval. Ibrexafungerp, currently approved for vulvovaginal candidiasis, has been studied off‐label for use in IC and candidemia, and initial data is encouraging. Lastly, fosmanogepix, a mechanistically novel, investigational antifungal agent, may be a potential future option in the management of IC and candidemia. Future research is needed to evaluate the potential use of these agents among diverse patient populations.

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

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

Cited by 20 publications

References 14 publications

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

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

Incidence of Candidemia Is Higher in COVID-19 versus Non-COVID-19 Patients, but Not Driven by Intrahospital Transmission

Management of invasive candidiasis: A focus on rezafungin, ibrexafungerp, and fosmanogepix

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