Detection of Amphotericin B Resistance in Candida haemulonii and Closely Related Species by Use of the Etest, Vitek-2 Yeast Susceptibility System, and CLSI and EUCAST Broth Microdilution Methods

Shin, Jong Hee; Kim, Mina; Jang, Sook Jin; Ju, Min; Kim, Soo Hyun; Shin, Myung Geun; Suh, Soon Pal; Ryang, Dong‐Wook

doi:10.1128/jcm.06440-11

Cited by 53 publications

(45 citation statements)

References 19 publications

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“…Notably, the reference CLSI-BMD method in the present series showed reduced AMB MICs in 84% of C. auris isolates. Similarly, low AMB MICs (0.25 to 1 g/ml) by CLSI-BMD were reported for 20 C. auris isolates from South Korea by Shin et al (25). However, these authors observed a high EA (100%) between the CLSI-BMD and Vitek method for AMB, which is in contrast with the observations in the present study.…”

Section: Discussioncontrasting

confidence: 56%

“…However, these authors observed a high EA (100%) between the CLSI-BMD and Vitek method for AMB, which is in contrast with the observations in the present study. This deviation could be attributed to the low number of isolates tested (25). Major errors of azole susceptibility in 218 isolates of 5 Candida species using another commercial automated reading system (ATB FUNGUS 3) have been reported recently from China, resulting in pseudohigh rates of antifungal resistance (26).…”

Section: Discussionmentioning

confidence: 99%

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Multidrug-Resistant Candida auris Misidentified as Candida haemulonii: Characterization by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and DNA Sequencing and Its Antifungal Susceptibility Profile Variability by Vitek 2, CLSI Broth Microdilution, and Etest Method

et al. 2015

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dCandida auris is a multidrug-resistant yeast that causes a wide spectrum of infections, especially in intensive care settings. We investigated C. auris prevalence among 102 clinical isolates previously identified as Candida haemulonii or Candida famata by the Vitek 2 system. Internal transcribed spacer region (ITS) sequencing confirmed 88.2% of the isolates as C. auris, and matrixassisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) easily separated all related species, viz., C. auris (n ‫؍‬ 90), C. haemulonii (n ‫؍‬ 6), C. haemulonii var. vulnera (n ‫؍‬ 1), and Candida duobushaemulonii (n ‫؍‬ 5). The in vitro antifungal susceptibility was determined using CLSI broth microdilution (CLSI-BMD), the Vitek 2 antifungal susceptibility test, and the Etest method. C. auris isolates revealed uniformly elevated fluconazole MICs (MIC 50 , 64 g/ml), and an alarming percentage of isolates (37%) exhibited elevated caspofungin MICs by CLSI-BMD. Notably, 34% of C. auris isolates had coexisting elevated MICs (>2 g/ml) for both fluconazole and voriconazole, and 10% of the isolates had elevated coexisting MICs (>2 g/ml) to two additional azoles, i.e., posaconazole and isavuconazole. In contrast to reduced amphotericin B MICs by CLSI-BMD (MIC 50 , 1 g/ml) for C. auris, elevated MICs were noted by Vitek 2 (MIC 50 , 8 g/ml), which were statistically significant. Candida auris remains an unnoticed pathogen in routine microbiology laboratories, as 90% of the isolates characterized by commercial identification systems are misidentified as C. haemulonii. MALDI-TOF MS proved to be a more robust diagnostic technique for rapid identification of C. auris. Considering that misleading elevated MICs of amphotericin B by the Vitek AST-YS07 card may lead to the selection of inappropriate therapy, a cautionary approach is recommended for laboratories relying on commercial systems for identification and antifungal susceptibility testing of rare yeasts. In recent years, two species, namely, Candida pseudohaemulonii and Candida auris, which are phylogenetically closely related to Candida haemulonii in the Metschnikowiaceae clade, have been described (1). The yeast C. auris, isolated from the external ear canal of a Japanese patient, was described as a new species in 2009 (2). This pathogen was recently recognized as an emerging multidrug-resistant (MDR) yeast that can cause a wide spectrum of infections, ranging from fungemia to deep-seated infections, especially in intensive care settings (3-8). Candida auris is reported to be misidentified as C. haemulonii, Candida famata, and Rhodotorula glutinis by commercial identification systems, such as Vitek 2 and API20C-AUX, and exhibits a unique susceptibility profile (5-8). Notably, the potential of clonal transmission of C. auris, highly elevated MICs to fluconazole, and reduced susceptibility to voriconazole, caspofungin, and flucytosine are matters of serious concern (7-9). Therefore, accurate identification is important, because treatment strategies are often directed ...

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Multidrug-Resistant Candida auris Misidentified as Candida haemulonii: Characterization by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and DNA Sequencing and Its Antifungal Susceptibility Profile Variability by Vitek 2, CLSI Broth Microdilution, and Etest Method

et al. 2015

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“…In an earlier work, Shin et al. () used 38 species of Candida including 20 C. auris isolates to evaluate the capacity of five phenotypic tests namely, E‐test on Mueller‐Hinton agar supplemented with glucose and methylene blue (E‐test‐MH), E‐test on RPMI agar supplemented with 2% glucose (E‐test‐RPG), Vitek 2, as well as CLSI and EUCAST MBD protocols to determine AMB resistance in vitro. The E‐test‐MH method was adjudged the best in detecting AMB resistance followed by the Vitek 2 among C. haemulonii and C. auris .…”

Section: Diagnostics and Typing Methodsmentioning

confidence: 99%

“…The E‐test‐MH method was adjudged the best in detecting AMB resistance followed by the Vitek 2 among C. haemulonii and C. auris . The CLSI and EUCAST MBD protocols yielded very narrow AMB MICs, which made them unable to efficiently discriminate between AMB susceptible and resistant strains (Shin et al., ). Further tests will be necessary to confirm this preliminary finding.…”

Section: Diagnostics and Typing Methodsmentioning

confidence: 99%

Candida auris: A systematic review and meta‐analysis of current updates on an emerging multidrug‐resistant pathogen

2018

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From 2009, Candida auris has emerged as a multidrug‐resistant ascomycete yeast pathogen with the capacity for easy transmission between patients and hospitals, as well as persistence on environmental surfaces. Its association with high mortalities, breakthrough and persistent candidaemia, inconsistencies in susceptibility testing results, misidentification by available commercial identification systems and treatment failure, complicates its management and detection. Within the last nine years, C. auris has been increasingly reported from far‐Eastern Asia, the Middle East, Africa, Europe, South and North America with substantial fatalities and misidentification. Herein, I provide a systematic and thorough review of this emerging pathogen. Meta‐analysis showed that at least 742 C. auris isolates have been reported in 16 countries, with most of these being from India (≥243), USA (≥232) and UK (≥103) (p‐value = .0355) within 2013–2017. Most isolates were from males (64.76%) (p‐value = .0329) and blood (67.48%) (p‐value < .0001), with substantial crude mortality (29.75%) (p‐value = .0488). Affected patients presented with other comorbidities: diabetes (≥52), sepsis (≥48), lung diseases (≥39), kidney diseases (≥32) etc. (p‐value < .0001). Resistance to fluconazole (44.29%), amphotericin B (15.46%), voriconazole (12.67%), caspofungin (3.48%) etc. were common (p‐value = .0059). Commonly used diagnostic tools included PCR (30.38%), Bruker MALDI‐TOF MS (14.00%), Vitek 2 YST ID (11.93%), AFLP (11.55%) and WGS (10.04%) (p‐value = .002). Multidrug resistance, high attributable mortality and persistence are associated with C. auris infections. Two novel drugs, SCY‐078 and VT‐1598, are currently in the pipeline. Contact precautions, strict infection control, periodic surveillance and cleaning with chlorine‐based detergents, efficient, faster and cheaper detection tools are necessary for prevention, containment and early diagnosis of C. auris infections.

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“…So far, the majority of the MIC data for C. auris isolates reported worldwide have been based on the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, and only a very few, limited to amphotericin B, have been based on the European Committee for Antimicrobial Susceptibility Testing (EUCAST) reference method (16). MICs obtained by the CLSI and EUCAST methods show a good correlation for Candida species and fluconazole and voriconazole in general, whereas MICs obtained by the EUCAST method are typically lower for amphotericin B, anidulafungin, micafungin, and posaconazole (17,18).…”

mentioning

confidence: 99%

Comparison of EUCAST and CLSI Reference Microdilution MICs of Eight Antifungal Compounds for Candida auris and Associated Tentative Epidemiological Cutoff Values

Arendrup

Prakash

Meletiadis

et al. 2017

Antimicrob Agents Chemother

209

189

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Candida auris is an emerging multidrug-resistant yeast. So far, all but two susceptibility testing studies have examined Յ50 isolates, mostly with the CLSI method. We investigated CLSI and EUCAST MICs for 123 C. auris isolates and eight antifungals and evaluated various methods for epidemiological cutoff (ECOFF) determinations. MICs (in milligrams per liter) were determined using CLSI method M27-A3, and the EUCAST E.Def 7.3. ANOVA analysis of variance with Bonferroni's multiple-comparison test and Pearson analysis were used on log 2 MICs (significance at P values of Ͻ0.05). The percent agreement (within Ϯ0 to Ϯ2 2-fold dilutions) between the methods was calculated. ECOFFs were determined visually, statistically (using the ECOFF Finder program and MicDat1.23 software with 95% to 99% endpoints), and via the derivatization method (dECOFFs). The CLSI and EUCAST MIC distributions were wide, with several peaks for all compounds except amphotericin B, suggesting possible acquired resistance. Modal MIC, geometric MIC, MIC 50 , and MIC 90 values were Յ1 2-fold dilutions apart, and no significant differences were found. The quantitative agreement was best for amphotericin B (80%/97% within Ϯ1/Ϯ2 dilutions) and lowest for isavuconazole and anidulafungin (58%/76% to 75% within Ϯ1/Ϯ2 dilutions). We found that 90.2%/100% of the isolates were amphotericin B susceptible based on CLSI/EUCAST methods, respectively (i.e., with MICs of Յ1 mg/liter), and 100%/ 97.6% were fluconazole nonsusceptible by CLSI/EUCAST (MICs Ͼ 2). The ECOFFs (in milligrams per liter) were similar across the three different methods for itraconazole (ranges for CLSI/EUCAST, 0.25 to 0.5/0.5 to 1), posaconazole (0.125/0.125 to 0.25), amphotericin B (0.25 to 0.5/1 to 2), micafungin (0.25 to 0.5), and anidulafungin (0.25 to 0.5/0.25 to 1). In contrast, the estimated ECOFFs were dependent on the method applied for voriconazole (1 to 32) and isavuconazole (0.125 to 4). CLSI and EUCAST MICs were remarkably similar and confirmed uniform fluconazole resistance and variable acquired resistance to the other agents.

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Detection of Amphotericin B Resistance in Candida haemulonii and Closely Related Species by Use of the Etest, Vitek-2 Yeast Susceptibility System, and CLSI and EUCAST Broth Microdilution Methods

Cited by 53 publications

References 19 publications

Multidrug-Resistant Candida auris Misidentified as Candida haemulonii: Characterization by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and DNA Sequencing and Its Antifungal Susceptibility Profile Variability by Vitek 2, CLSI Broth Microdilution, and Etest Method

Multidrug-Resistant Candida auris Misidentified as Candida haemulonii: Characterization by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and DNA Sequencing and Its Antifungal Susceptibility Profile Variability by Vitek 2, CLSI Broth Microdilution, and Etest Method

Candida auris: A systematic review and meta‐analysis of current updates on an emerging multidrug‐resistant pathogen

Comparison of EUCAST and CLSI Reference Microdilution MICs of Eight Antifungal Compounds for Candida auris and Associated Tentative Epidemiological Cutoff Values

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