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Background: Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis., Objective: The 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 ., Methods: Ibrexafungerp, 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., Results: Ibrexafungerp 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/MIC 50 s (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 ., Conclusion: Ibrexafungerp showed a potent in vitro activity against Candida ., Competing Interests: Outside the current study, we declare the following potential conflicts: GQ has received research grants from Astellas Pharma, Pfizer, Merck Sharp & Dohme, and SCYNEXIS. GQ has served on advisory/consultant boards for Merck, Sharp & Dohme, and SCYNEXIS, and he has received speaker honoraria from Abbvie, Astellas Pharma, Merck Sharp & Dohme, Pfizer, and SCYNEXIS. KB-E and DA are employed by SCYNEXIS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Quindós, Miranda-Cadena, San-Millán, Borroto-Esoda, Cantón, Linares-Sicilia, Hamprecht, Montesinos, Tortorano, Prigitano, Vidal-García, Marcos-Arias, Guridi, Sanchez-Reus, Machuca-Bárcena, Rodríguez-Iglesias, Martín-Mazuelos, Castro-Méndez, López-Soria, Ruiz-Gaitán, Fernandez-Rivero, Lorenzo, Capilla, Rezusta, Pemán, Guarro, Pereira, Pais, Romeo, Ezpeleta, Jauregizar, Angulo and Eraso.)

Objectives: We aimed to assess the percentage of azole resistance in Aspergillus fumigatus in Spain., Methods: Thirty participating Spanish hospitals stored all morphologically identified A. fumigatus sensu lato clinical isolates-regardless their clinical significance-from 15 February to 14 May 2019. Isolates showing azole resistance according to the EUCAST 9.3.2 methodology were molecularly identified and the cyp51A gene was studied in A. fumigatus sensu stricto isolates., Results: Eight hundred and forty-seven isolates from 725 patients were collected in 29 hospitals (A. fumigatus sensu stricto (n = 828) and cryptic species (n = 19)). Isolates were mostly from the lower respiratory tract (94.0%; 797/847). Only cryptic species were amphotericin B resistant. Sixty-three (7.4%) out of the 847 isolates were resistant to ≥1 azole(s). Azole resistance was higher in cryptic species than in A. fumigatus sensu stricto (95%, 18/19 vs. 5.5%, 45/828); isavuconazole was associated to the lowest number of non-wild type isolates. The dominant mechanism of resistance was the presence of TR 34 -L98H substitutions (n = 24 out of 63). Out of the 725 patients, 48 (6.6%) carried either cryptic species (n = 14) or A. fumigatus sensu stricto (n = 34; 4.7%) resistant isolates. Aspergillus fumigatus sensu stricto harbouring either the TR 34 -L98H (n = 19) or TR 46 /Y121F/T289A (n = 1) mutations were detected in patients in hospitals located at 7/24 studied cities., Discussion: Of the patients, 6.6% carry azole-resistant A. fumigatus sensu lato isolates in Spain. TR 34 -L98H is the dominant cyp51A gene substitutions, although its presence is not widespread., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans , 215  C. dubliniensis , 4,418  C. glabrata species complex, 157  C. guilliermondii ( Meyerozyma guilliermondii ), 676  C. krusei ( Pichia kudriavzevii ), 298  C. lusitaniae ( Clavispora lusitaniae ), 911  C. parapsilosis sensu stricto , 3,691  C. parapsilosis species complex, 36  C. metapsilosis , 110  C. orthopsilosis , 1,854  C. tropicalis , 244 Saccharomyces cerevisiae , 1,409 Aspergillus fumigatus , 389  A. flavus , 130  A. nidulans , 233  A. niger , and 302  A. terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 ( C. albicans ), ERG11 and MRR1 ( C. parapsilosis ), cyp51A ( A. fumigatus ), and CDR2 and CDR1 overexpression ( C. albicans and C. glabrata , respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 µg/ml for C. albicans and the Etest itraconazole ECV of 2 µg/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants., (Copyright © 2018 American Society for Microbiology.)

Background: Saprochaete capitata (formerly known as Geotrichum capitatum and Blastoschizomyces capitatus) is a ubiquitous fungus found in soil, water, air, plants and dairy products. It colonizes the skin, and bronchial and intestinal tract of healthy people producing serious opportunistic infections in patients with haematological malignancies, especially in those with acute leukaemia. Since 1960s its presence is being increasingly recognized in this group of patients. The clinical spectrum of S. capitata disseminated infections is very similar to that produced by Candida, being easily misinterpreted. The associated high mortality and low susceptibility to fluconazole and echinocandins of S. capitata require the acknowledgement of this emergent infection so that it can be properly treated., Case Report: We report 5 new cases of S. capitata disseminated infection in patients with advanced haematological malignancies observed in the haematology unit between the years 2004 and 2010, and review the state-of-the-art for diagnosis and treatment of this infection., Conclusions: Based on our experience, the prophylactic use of or the empirical antifungal treatment with fluconazole and/or echinocandins would not be adequate for oncohaematological patients in those hospitals where S. capitata infection may be highly prevalent., (Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)