Real-World Experience with Echinocandin MICs against Candida Species in a Multicenter Study of Hospitals That Routinely Perform Susceptibility Testing of Bloodstream Isolates

Eschenauer, Gregory A.; Nguyen, M. Hong; Shoham, Shmuel; Vázquez, José Antonio; Morris, Arthur J.; Pasculle, William; Kubin, Christine J.; Klinker, Kenneth P.; Carver, Peggy L.; Hanson, Kimberly E.; Chen, Sharon; Lam, Simon W.; Potoski, Brian A.; Clarke, Lloyd; Shields, Ryan K.; Clancy, Cornelius J.

doi:10.1128/aac.02163-13

Cited by 58 publications

(61 citation statements)

References 17 publications

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“…The C. albicans isolate was found to harbor a point mutation (S645F) in HS1 of fks1, whereas the C. guilliermondii isolate (except for a constitutive polymorphism) and the C. krusei isolate were wild type for the fks gene; of note, the C. guilliermondii isolate showed an intermediate phenotype for susceptibility to caspofungin and anidulafungin (Table 3). It was noticed that adoption of the revised CLSI CBPs for caspofungin may overstate the rates at which isolates are nonsusceptible (especially intermediate) to caspofungin among C. glabrata and C. krusei isolates (18), and the interlaboratory variability in caspofungin MICs for C. albicans, C. glabrata, C. tropicalis, and C. krusei may considerably limit the use of both the CLSI and EUCAST reference methods (42). Thus, while clinical microbiology laboratories should use micafungin or anidulafungin as a surrogate marker to predict caspofungin susceptibility (43,44), the use of SYO assays was recently advised for hospitals that routinely perform echinocandin susceptibility testing of bloodstream isolates (18).…”

Section: Resultsmentioning

confidence: 99%

Antifungal Susceptibility Profiles of Bloodstream Yeast Isolates by Sensititre YeastOne over Nine Years at a Large Italian Teaching Hospital

Posteraro

Spanu

Fiori

et al. 2015

Antimicrob Agents Chemother

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Sensititre YeastOne (SYO) is an affordable alternative to the Clinical and Laboratory Standards Institute (CLSI) reference method for antifungal susceptibility testing. In this study, the MICs of yeast isolates from 1,214 bloodstream infection episodes, generated by SYO during hospital laboratory activity (January 2005 to December 2013), were reanalyzed using current CLSI clinical breakpoints/epidemiological cutoff values to assign susceptibility (or the wild-type [WT] phenotype) to systemic antifungal agents. Excluding Candida albicans (57.4% of all isolates [n ‫؍‬ 1,250]), the most predominant species were Candida parapsilosis complex (20.9%), Candida tropicalis (8.2%), Candida glabrata (6.4%), Candida guilliermondii (1.6%), and Candida krusei (1.3%). Among the non-Candida species (1.9%), 7 were Cryptococcus neoformans and 17 were other species, mainly Rhodotorula species. Over 97% of Candida isolates were susceptible (WT phenotype) to amphotericin B and flucytosine. Rates of susceptibility (WT phenotype) to fluconazole, itraconazole, and voriconazole were 98.7% in C. albicans, 92.3% in the C. parapsilosis complex, 96.1% in C. tropicalis, 92.5% in C. glabrata, 100% in C. guilliermondii, and 100% (excluding fluconazole) in C. krusei. The fluconazole-resistant isolates consisted of 6 C. parapsilosis complex isolates, 3 C. glabrata isolates, 2 C. albicans isolates, 2 C. tropicalis isolates, and 1 Candida lusitaniae isolate. Of the non-Candida isolates, 2 C. neoformans isolates had the non-WT phenotype for susceptibility to fluconazole, whereas Rhodotorula isolates had elevated azole MICs. Overall, 99.7% to 99.8% of Candida isolates were susceptible (WT phenotype) to echinocandins, but 3 isolates were nonsusceptible (either intermediate or resistant) to caspofungin (C. albicans, C. guilliermondii, and C. krusei), anidulafungin (C. albicans and C. guilliermondii), and micafungin (C. albicans). However, when the intrinsically resistant non-Candida isolates were included, the rate of echinocandin nonsusceptibility reached 1.8%. In summary, the SYO method proved to be able to detect yeast species showing antifungal resistance or reduced susceptibility.

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Section: Resultsmentioning

confidence: 99%

Antifungal Susceptibility Profiles of Bloodstream Yeast Isolates by Sensititre YeastOne over Nine Years at a Large Italian Teaching Hospital

Posteraro

Spanu

Fiori

et al. 2015

Antimicrob Agents Chemother

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“…Although this variability can be observed among different species, the differences are most pronounced with C. glabrata and C. krusei (1,2,12). The issue of variable caspofungin MICs is important to address because of the lowering of the CLSI clinical breakpoints for the echinocandins against most Candida species.…”

Section: Discussionmentioning

confidence: 99%

Effects of Treated versus Untreated Polystyrene on Caspofungin In Vitro Activity against Candida Species

et al. 2016

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Significant interlaboratory variability is observed in testing the caspofungin susceptibility of Candida species by both the CLSI and EUCAST broth microdilution methodologies. We evaluated the influence of treated versus untreated polystyrene microtiter trays on caspofungin MICs using 209 isolates of four Candida species, including 16 C. albicans and 11 C. glabrata isolates with defined FKS mutations. Caspofungin MICs were also determined using the commercially available YeastOne and Etest assays and 102 isolates. All C. glabrata isolates had caspofungin MICs of >0.5 g/ml, the clinical breakpoint for caspofungin resistance in this species, measured using trays made of treated polystyrene, regardless of the FKS status. In contrast, susceptible isolates could readily be distinguished from resistant/non-wild-type isolates when caspofungin MICs were measured using untreated polystyrene trays and both the YeastOne and Etest assays. Similar results were also observed for C. krusei isolates, as all isolates had caspofungin MICs above the threshold for resistance measured using treated polystyrene trays. In contrast, C. albicans isolates could be correctly identified as susceptible or resistant when caspofungin MICs were measured with treated or untreated trays and with the YeastOne and Etest assays. MICs falsely elevated above the resistance breakpoint were also not observed for C. tropicalis isolates. These results demonstrated that the use of treated polystyrene may be one factor that leads to falsely elevated caspofungin in vitro susceptibility results and that this may also be a greater issue for some Candida species than for others. Significant interlaboratory variability has been reported for caspofungin susceptibility testing, with some laboratories reporting MIC values elevated above the revised CLSI clinical breakpoints (1). The interlaboratory variability is not without consequences, as it may result in major errors for caspofungin use (i.e., falsely interpreting an isolate as resistant to this echinocandin). In a retrospective review of our antifungal susceptibility database using data from 2008 to 2012, we found that 95.6% of C. glabrata and 74.3% of C. krusei isolates would be classified as resistant to caspofungin on the basis of the revised CLSI echinocandin clinical breakpoints (2). Other laboratories have reported similar results (3). As the factors that lead to interlaboratory variability are unknown, we sought to determine if the choice of plastic used in the microtiter trays, either treated or untreated polystyrene, could affect caspofungin MIC values. These trays are designed for cell cultures, and treatment of the plastic, either by coating or corona discharge to impart an electrical charge to the plastic, allows the cells to adhere. Our laboratory has historically used 96-well microtiter trays made of treated polystyrene, while other laboratories have used those made of untreated plastic. The CLSI M27-A3 standard for yeast antifungal susceptibility testing has not addressed plastic type or recomm...

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“…The CLSI further suggested that either micafungin or anidulafungin MIC CBPs can be used as predictors of susceptibility or resistance of Candida species to caspofungin. assays in hospitals may reduce the interlaboratory variability in caspofungin MICs against Candida species (28). Among the 14 patients with candidemia due to fluconazoleresistant Candida species, half of the patients had previous exposure to fluconazole.…”

Section: Discussionmentioning

confidence: 99%

Antifungal Susceptibilities of Candida Isolates Causing Bloodstream Infections at a Medical Center in Taiwan, 2009-2010

Huang

Liu

Liao

et al. 2014

Antimicrob Agents Chemother

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Nearly all isolates of C. albicans, C. parapsilosis, and C. krusei were susceptible to voriconazole; however, rates of voriconazole susceptibility were 78.6% in C. tropicalis. Few isolates of C. albicans (n ‫؍‬ 5; 2.1%) and C. glabrata (n ‫؍‬ 3; 3.9%), no isolates of C. parapsilosis, C. krusei, and C. guilliermondii, but 62.2% (n ‫؍‬ 51) of C. tropicalis isolates were non-wild type for posaconazole susceptibility. For itraconazole susceptibility, 98.3% of C. albicans isolates were wild type, and 3.9% (n ‫؍‬ 3) of C. glabrata isolates were non-wild type. Almost all of the isolates tested (>97% for all species) were susceptible to both micafungin and anidulafungin. All isolates tested were found to be wild type for amphotericin B susceptibility, with MICs of <1g/ml. Further evaluation is needed to establish CBPs of antifungal agents by the 24-h SYO method for the management of patients with candidemia or other invasive candida infections.

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Real-World Experience with Echinocandin MICs against Candida Species in a Multicenter Study of Hospitals That Routinely Perform Susceptibility Testing of Bloodstream Isolates

Cited by 58 publications

References 17 publications

Antifungal Susceptibility Profiles of Bloodstream Yeast Isolates by Sensititre YeastOne over Nine Years at a Large Italian Teaching Hospital

Antifungal Susceptibility Profiles of Bloodstream Yeast Isolates by Sensititre YeastOne over Nine Years at a Large Italian Teaching Hospital

Effects of Treated versus Untreated Polystyrene on Caspofungin In Vitro Activity against Candida Species

Antifungal Susceptibilities of Candida Isolates Causing Bloodstream Infections at a Medical Center in Taiwan, 2009-2010

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