Intra- and Interlaboratory Agreement in Assessing the In Vitro Activity of Micafungin against Common and Rare Candida Species with the EUCAST, CLSI, and Etest Methods

Abstract

dThe emergence of resistant strains among common and rare Candida species necessitates continuous monitoring of the in vitro susceptibilities of those isolates. We therefore assessed the in vitro activities of micafungin against 1,099 molecularly identified isolates belonging to 5 common and 20 rare Candida species by the EUCAST, CLSI, and Etest methods, assessing both the intralaboratory agreement and the interlaboratory agreement for two centers. The median micafungin EUCAST MICs were as follows, from the lowest to the highest: for Candida albicans, 0.004 mg/liter; for C. glabrata, 0.016 mg/liter; for C. tropicalis, 0.031 mg/liter; for C. krusei, 0.125 mg/liter; for C. parapsilosis, 2 mg/liter. Among rare Candida species, high MICs were found for C. guilliermondii, C. lipolytica, C. orthopsilosis, C. metapsilosis, and C. fermentati. No resistant isolates were found by the CLSI method, whereas resistance rates of 1 to 2% were found by the EUCAST method. Overall, the EUCAST method resulted in MICs 1 to 2 dilutions higher than those found by the CLSI and Etest methods. The intra-and interlaboratory agreement between methods was >92%, except for the interlaboratory agreement between the EUCAST and CLSI methods (81%), where 17 to 31% of the differences were >2 2-fold dilutions for C. albicans, C. glabrata, C. tropicalis, and other rare Candida species and <6% for C. parapsilosis and C. krusei. For the other interlaboratory comparisons, the EUCAST method resulted in higher MICs than the Etest method for all species, but <7% of these differences were >2 2-fold dilutions. Overall, the CLSI method resulted in lower MICs than the Etest method, with 11% of all isolates demonstrating >2 2-fold-dilution differences (6 to 20% for C. albicans, C. tropicalis, and rare Candida species; <5% for C. glabrata, C. krusei, and C. parapsilosis) and smaller differences found after 24 h. Despite these differences, categorical agreement was excellent (>97%), with only 1 to 2% very major errors between the EUCAST method and the other two methods. Micafungin is an echinocandin used for the treatment and prophylaxis of Candida infections in both neutropenic and nonneutropenic patients (1, 2). Although micafungin has a broad spectrum of activity against different Candida species, including azole-resistant isolates, the emergence of resistance in common and rare Candida species necessitates in vitro susceptibility testing of those isolates (3). Methods for the determination of MICs have recently been published by the Clinical and Laboratory Standards Institute (CLSI) (4) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (5). Both of these methods are broth microdilution methods; they differ in glucose concentration, inoculum size, the shape of microplates, and the mode of reading. In addition, the Etest is often used to determine susceptibility in routine laboratories (6).Although all these methods are reproducible and reliable in testing the in vitro susceptibility of Candida isolates, there are few comparative stu...

Etest and Sensititre YeastOne Susceptibility Testing of Echinocandins against Candida Species from a Single Center in Austria

“…In contrast, with a large collection of Ͼ1,000 Candida isolates tested against micafungin, EUCAST MICs were shown to be 1 to 2 dilutions higher than those observed by Etest (13). However, as in our study, these MIC differences did not effectively influence CA and the susceptibility classification of isolates.…”

“…Differences in MICs obtained by different laboratories have been described as being Ͼ2 2-fold dilutions (13). Minor MIC differences without a major impact on the final susceptibility result may be due to interlaboratory variability rather than to real differences in action among the echinocandins.…”

In Vitro Antifungal Susceptibility Testing of Candida Isolates with the EUCAST Methodology, a New Method for ECOFF Determination

“…Since WT distributions and ECOFFs are species specific, all strains were reidentified in our laboratory using molecular techniques, including amplified fragment length polymorphism (AFLP) and the internal transcribed spacer (ITS) technique, where appropriate (5). In total, 584 strains (53.1%) were identified as C. albicans, 180 (16.4%) as C. tropicalis, 122 (11.1%) as C. parapsilosis, 86 (7.8%) as C. glabrata, and 30 (2.7%) as C. krusei, as previously described (6) (6). No C. dubliniensis and no C. glabrata cryptic species were found, whereas within the C. parapsilosis complex (n ϭ 140), 87.2% (n ϭ 122) were C. parapsilosis sensu stricto, 10.7% (n ϭ 15) were C. orthopsilosis, and 2.1% (n ϭ 3) were C. metapsilosis.…”

First report on echinocandin resistant Polish Candida isolates

“…According to a variety of data, C. palmioleophila could be resistant to fluconazole and susceptible to other antimycotics, e.g. echinocandins (Liu et al, 2017;Meletiadis et al, 2016), but there is also some information about elevated caspofungin MIC of C. palmioleophila (Brilhante et al, 2017). C. palmioleophila were found in animal microflora (Sokół et al, 2018) and there are only a few data available on C. palmioleophila as an etiological agent of human infections (Trouvé et al, 2017).…”