Wild-Type MIC Distributions and Epidemiological Cutoff Values for the Echinocandins and
            <i>Candida</i>
            spp

Pfaller, Michael A.; Boyken, L.; Hollis, Richard J.; Kroeger, J.; Messer, S. A.; Tendolkar, S.; Jones, Ronald N.; Turnidge, John; Diekema, Daniel J.

doi:10.1128/jcm.01590-09

Cited by 156 publications

(160 citation statements)

References 28 publications

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“…The recently described CLSI ECVs for each agent and species (25,28) were used to obtain CA percentages between the MIC values determined with the EUCAST method and those determined by the CLSI method. The ECV for each triazole and each species of Candida was obtained by considering the WT MIC distribution (population of strains with no acquired resistance mechanisms), the modal MIC for each distribution, and the inherent variability of the test (25)(26)(27)(28). In general, the ECV encompasses at least 95% of isolates in the WT distribution (36).…”

Section: Methodsmentioning

confidence: 99%

“…The upper limit to the WT distribution is defined as the ECV. Organisms with acquired resistance mechanisms may be included among those for which the MICs are higher than the ECVs (14,15,25,26).…”

Section: % [Eucast]) Duration Of Incubation (24 and 48 H [Clsi] Vermentioning

confidence: 99%

“…ECVs (24 h) for posaconazole and Candida have been defined by the CLSI (28) but are not yet available for the EUCAST method. The WT MIC distribution for a species is defined as the MIC distribution for isolates that exhibit no acquired or mutational resistance to the drug in question, whereas the non-WT isolates may possess acquired or mutational resistance mechanisms (11,12,14,15,25,26,36,37). The upper limit to the WT distribution is defined as the ECV.…”

Section: % [Eucast]) Duration Of Incubation (24 and 48 H [Clsi] Vermentioning

confidence: 99%

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Comparison of the Broth Microdilution (BMD) Method of the European Committee on Antimicrobial Susceptibility Testing with the 24-Hour CLSI BMD Method for Testing Susceptibility of Candida Species to Fluconazole, Posaconazole, and Voriconazole by Use of Epidemiological Cutoff Values

et al. 2011

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The antifungal broth microdilution (BMD) method of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) was compared with CLSI BMD method M27-A3 for fluconazole, posaconazole, and voriconazole susceptibility testing of 1,056 isolates of Candida. The isolates were obtained in 2009 from more than 60 centers worldwide and included 560 isolates of C. albicans, 175 of C. glabrata, 162 of C. parapsilosis, 124 of C. tropicalis, and 35 of C. krusei. The overall essential agreement (EA) between EUCAST and CLSI results ranged from 96.9% (voriconazole) to 98.6% (fluconazole). The categorical agreement (CA) between methods and species of Candida was assessed using previously determined epidemiological cutoff values (ECVs). The ECVs (expressed as g/ml) for fluconazole, posaconazole, and voriconazole, respectively, were as follows: 0.12, 0.06, and 0.03 for C. albicans; 32, 2, and 0.5 for C. glabrata; 2, 0.25, and 0.12 for C. parapsilosis; 2, 0.12, and 0.06 for C. tropicalis; 64, 0.5, and 0.5 for C. krusei. Excellent CA was observed for all comparisons between the EUCAST and CLSI results for fluconazole, posaconazole, and voriconazole, respectively, for each species: 98.9%, 93.6%, and 98.6% for C. albicans; 96.0%, 98.9%, and 93.7% for C. glabrata; 90.8%, 98.1%, and 98.1% for C. parapsilosis; 99.2%, 99.2%, and 96.8% for C. tropicalis; 97.1%, 97.1%, and 97.1% for C. krusei. We demonstrate high levels of EA and CA between the CLSI and EUCAST BMD methods for testing of triazoles against Candida when the MICs were determined after 24 h and ECVs were used to differentiate wild-type (WT) from non-WT strains. These results provide additional data in favor of the harmonization of these two methods.The triazole class of antifungal agents includes fluconazole, posaconazole, and voriconazole. Each of these agents has good in vitro and clinical activity against most species of Candida (3, 32). Despite the broad utilization of these agents in the prevention and treatment of invasive candidiasis (2,6,16,34), longitudinal surveillance studies have documented the sustained potency of all three triazoles since the introduction of fluconazole in 1990 (8, 9, 18, 21, 25, 28, 31). Although resistance to the triazoles remains relatively uncommon among cases of invasive candidiasis (IC) (19,23,25), numerous examples of clinical failure associated with elevated MICs to one or more of these agents have been reported (1,17,20,22,23,27). Indeed, one of the pressing concerns surrounding this class of antifungal agents is the emergence of cross-resistance within the class, particularly involving IC due to C. glabrata (1,17,19,20,23,24,35).Currently, there are two independent standards for broth microdilution (BMD) antifungal susceptibility testing of the triazoles against Candida species: the Clinical and Laboratory Standards Institute (CLSI) method (5) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method (30).The two methods are similar in that both use BMD, RPMI 1640 broth, 35 to 37°C incubation temperatur...

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Section: Methodsmentioning

confidence: 99%

Section: % [Eucast]) Duration Of Incubation (24 and 48 H [Clsi] Vermentioning

confidence: 99%

Section: % [Eucast]) Duration Of Incubation (24 and 48 H [Clsi] Vermentioning

confidence: 99%

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Comparison of the Broth Microdilution (BMD) Method of the European Committee on Antimicrobial Susceptibility Testing with the 24-Hour CLSI BMD Method for Testing Susceptibility of Candida Species to Fluconazole, Posaconazole, and Voriconazole by Use of Epidemiological Cutoff Values

et al. 2011

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“…The C. parapsilosis complex (C. parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis) and Candida guilliermondii display higher echinocandin MIC values relative to other susceptible Candida species (Pfaller et al 2008a(Pfaller et al , 2010Tortorano et al 2013). The mechanism underlying reduced echinocandin susceptibility involves naturally occurring polymorphisms in FKS hot-spot regions (GarciaEffron et al 2008).…”

Section: Hot-spot Polymorphisms and Inherent Reduced Susceptibilitymentioning

confidence: 99%

Mechanisms of Antifungal Drug Resistance

Cowen

Sanglard

Howard

et al. 2014

Cold Spring Harb Perspect Med

492

399

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Antifungal therapy is a central component of patient management for acute and chronic mycoses. Yet, treatment choices are restricted because of the sparse number of antifungal drug classes. Clinical management of fungal diseases is further compromised by the emergence of antifungal drug resistance, which eliminates available drug classes as treatment options. Once considered a rare occurrence, antifungal drug resistance is on the rise in many high-risk medical centers. Most concerning is the evolution of multidrug-resistant organisms refractory to several different classes of antifungal agents, especially among common Candida species. The mechanisms responsible are mostly shared by both resistant strains displaying inherently reduced susceptibility and those acquiring resistance during therapy. The molecular mechanisms include altered drug affinity and target abundance, reduced intracellular drug levels caused by efflux pumps, and formation of biofilms. New insights into genetic factors regulating these mechanisms, as well as cellular factors important for stress adaptation, provide a foundation to better understand the emergence of antifungal drug resistance.

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“…CDR1 and CDR2 genes have been shown to be upregulated in resistant strains, leading to an enhanced efflux of the drug [10] and hence leading to resistance to multiple azoles [12,13]. Cross-resistance between fluconazole and other azoles has been reported [14][15][16], the mechanistic basis for this cross-resistance most often involves the upregulation of genes encoding the CDR pumps that act as ATP-binding cassette efflux transporters [13,17,18].…”

Section: Introductionmentioning

confidence: 99%

Association of ADH1 and DDR48 expression with azole resistance in Candida albicans

Mostafa

Awad

2014

int. arab. j antimicrob. agents

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Background: Candida albicans is a frequent opportunistic pathogenic fungus that causes mucosal and systemic infections. The alcohol dehydrogenase 1 (ADH1) and DDR48 genes were found to be upregulated in fluconazole resistant Candida albicans. Therefore, understanding the function of drug resistance of genes will help in the development of new antifungal agents that can reverse drug resistance. This study aimed to investigate the role of ADH1 and DDR48 genes in development of fluconazole resistant C. albicans.

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Wild-Type MIC Distributions and Epidemiological Cutoff Values for the Echinocandins and Candida spp

Abstract: We tested a global collection of Candida sp. strains against anidulafungin, caspofungin, and micafungin, using CLSI M27-A3 broth microdilution (BMD) methods, in order to define wild-type (

Cited by 156 publications

References 28 publications

Comparison of the Broth Microdilution (BMD) Method of the European Committee on Antimicrobial Susceptibility Testing with the 24-Hour CLSI BMD Method for Testing Susceptibility of Candida Species to Fluconazole, Posaconazole, and Voriconazole by Use of Epidemiological Cutoff Values

Comparison of the Broth Microdilution (BMD) Method of the European Committee on Antimicrobial Susceptibility Testing with the 24-Hour CLSI BMD Method for Testing Susceptibility of Candida Species to Fluconazole, Posaconazole, and Voriconazole by Use of Epidemiological Cutoff Values

Mechanisms of Antifungal Drug Resistance

Association of ADH1 and DDR48 expression with azole resistance in Candida albicans

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