<i>Candida auris</i>Candidemia in Kuwait, 2014

Emara, Maha; Ahmad, Suhail; Khan, Ziauddin; Joseph, Leena; Al‐Obaid, Inaam; Purohit, Prashant; Bafna, Ritu

doi:10.3201/eid2106.150270

Cited by 158 publications

(137 citation statements)

References 7 publications

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“…These findings are in agreement with those of recent studies from other investigators, who also reported that C. auris isolates were generally resistant or less susceptible to azoles but susceptible to echinocandins (2–6, 8, 9, 13, 14, 16). Our finding that amphotericin B demonstrated less activity against C.…”

Section: Discussionsupporting

confidence: 93%

The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation

Larkin

Hager

Chandra

et al. 2017

Antimicrob Agents Chemother

340

317

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Candida auris, a new multidrug-resistant Candida spp. which is associated with invasive infection and high rates of mortality, has recently emerged. Here, we determined the virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production) of 16 C. auris isolates and their susceptibilities to 11 drugs belonging to different antifungal classes, including a novel orally bioavailable 1,3-β-d-glucan synthesis inhibitor (SCY-078). We also examined the effect of SCY-078 on the growth, ultrastructure, and biofilm-forming abilities of C. auris. Our data showed that while the tested strains did not germinate, they did produce phospholipase and proteinase in a strain-dependent manner and had a significantly reduced ability to adhere and form biofilms compared to that of Candida albicans (P = 0.01). C. auris isolates demonstrated reduced susceptibility to fluconazole and amphotericin B, while, in general, they were susceptible to the remaining drugs tested. SCY-078 had an MIC90 of 1 mg/liter against C. auris and caused complete inhibition of the growth of C. auris and C. albicans. Scanning electron microscopy analysis showed that SCY-078 interrupted C. auris cell division, with the organism forming abnormal fused fungal cells. Additionally, SCY-078 possessed potent antibiofilm activity, wherein treated biofilms demonstrated significantly reduced metabolic activity and a significantly reduced thickness compared to the untreated control (P < 0.05 for both comparisons). Our study shows that C. auris expresses several virulence determinants (albeit to a lesser extent than C. albicans) and is resistant to fluconazole and amphotericin B. SCY-078, the new orally bioavailable antifungal, had potent antifungal/antibiofilm activity against C. auris, indicating that further evaluation of this antifungal is warranted.

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Section: Discussionsupporting

confidence: 93%

The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation

Larkin

Hager

Chandra

et al. 2017

Antimicrob Agents Chemother

340

317

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“…breakpoints have been set by EUCAST as well as by CLSI (susceptible, Յ2 mg/liter; resistant, Ͼ4 mg/liter), and for amphotericin B a susceptibility breakpoint of Յ1 mg/liter is generally used, although this has not been formally established. When we adopted these breakpoints, our data confirmed previously published findings, suggesting that C. auris is uniformly nonsusceptible to fluconazole (2,5,11,13,23,24) and is, in general, susceptible to amphotericin B (2,3,11,23,24). However, some surveys have reported higher amphotericin B nonsusceptibility rates.…”

Section: Discussionsupporting

confidence: 80%

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

214

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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“…C. auris was first isolated in Japan and described as a new species in 2009 ( 5 ). In 2011, it was described as a cause of fungemia in South Korea ( 4 ) and was later isolated from patients in India ( 2 ), South Africa ( 6 ), Kuwait ( 3 ), and Venezuela ( 1 ). …”

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confidence: 99%