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Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans , 215  C. dubliniensis , 4,418  C. glabrata species complex, 157  C. guilliermondii ( Meyerozyma guilliermondii ), 676  C. krusei ( Pichia kudriavzevii ), 298  C. lusitaniae ( Clavispora lusitaniae ), 911  C. parapsilosis sensu stricto , 3,691  C. parapsilosis species complex, 36  C. metapsilosis , 110  C. orthopsilosis , 1,854  C. tropicalis , 244 Saccharomyces cerevisiae , 1,409 Aspergillus fumigatus , 389  A. flavus , 130  A. nidulans , 233  A. niger , and 302  A. terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 ( C. albicans ), ERG11 and MRR1 ( C. parapsilosis ), cyp51A ( A. fumigatus ), and CDR2 and CDR1 overexpression ( C. albicans and C. glabrata , respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 µg/ml for C. albicans and the Etest itraconazole ECV of 2 µg/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants., (Copyright © 2018 American Society for Microbiology.)

A prospective, observational, multicentre study of invasive candidosis (IC) in surgical patients in intensive care units (ICUs) was conducted from 2006 to 2008 in 72 ICUs in 14 European countries. A total of 779 patients (62.5% males, median age 63 years) with IC were included. The median rate of candidaemia was 9 per 1000 admissions. In 10.8% the infection was already present at the time of admission to ICU. Candida albicans accounted for 54% of the isolates, followed by Candida parapsilosis 18.5%, Candida glabrata 13.8%, Candida tropicalis 6%, Candida krusei 2.5%, and other species 5.3%. Infections due to C. krusei (57.9%) and C. glabrata (43.6%) had the highest crude mortality rate. The most common preceding surgery was abdominal (51.5%), followed by thoracic (20%) and neurosurgery (8.2%). Candida glabrata was more often isolated after abdominal surgery in patients ≥60 years, and C. parapsilosis was more often isolated in neurosurgery and multiple trauma patients as well as children ≤1 year of age. The most common first-line treatment was fluconazole (60%), followed by caspofungin (18.7%), liposomal amphotericin B (13%), voriconazole (4.8%) and other drugs (3.5%). Mortality in surgical patients with IC in ICU was 38.8%. Multivariate analysis showed that factors independently associated with mortality were: patient age ≥60 years (hazard ratio (HR) 1.9, p 0.001), central venous catheter (HR 1.8, p 0.05), corticosteroids (HR 1.5, p 0.03), not receiving systemic antifungal treatment for IC (HR 2.8, p <0.0001), and not removing intravascular lines (HR 1.6, p 0.02)., (Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) have been established for several Candida spp. and the newer triazoles and echinocandins but are not yet available for older antifungal agents, such as amphotericin B, flucytosine, or itraconazole. We determined species-specific ECVs for amphotericin B (AMB), flucytosine (FC) and itraconazole (ITR) for eight Candida spp. (30,221 strains) using isolates from 16 different laboratories in Brazil, Canada, Europe, and the United States, all tested by the CLSI reference microdilution method. The calculated 24- and 48-h ECVs expressed in μg/ml (and the percentages of isolates that had MICs less than or equal to the ECV) for AMB, FC, and ITR, respectively, were 2 (99.8)/2 (99.2), 0.5 (94.2)/1 (91.4), and 0.12 (95.0)/0.12 (92.9) for C. albicans; 2 (99.6)/2 (98.7), 0.5 (98.0)/0.5 (97.5), and 2 (95.2)/4 (93.5) for C. glabrata; 2 (99.7)/2 (97.3), 0.5 (98.7)/0.5 (97.8), and 05. (99.7)/0.5 (98.5) for C. parapsilosis; 2 (99.8)/2 (99.2), 0.5 (93.0)/1 (90.5), and 0.5 (97.8)/0.5 (93.9) for C. tropicalis; 2 (99.3)/4 (100.0), 32 (99.4)/32 (99.3), and 1 (99.0)/2 (100.0) for C. krusei; 2 (100.0)/4 (100.0), 0.5 (95.3)/1 (92.9), and 0.5 (95.8)/0.5 (98.1) for C. lusitaniae; -/2 (100.0), 0.5 (98.8)/0.5 (97.7), and 0.25 (97.6)/0.25 (96.9) for C. dubliniensis; and 2 (100.0)/2 (100.0), 1 (92.7)/-, and 1 (100.0)/2 (100.0) for C. guilliermondii. In the absence of species-specific CBP values, these wild-type (WT) MIC distributions and ECVs will be useful for monitoring the emergence of reduced susceptibility to these well-established antifungal agents.

Anidulafungin Etest and CLSI MICs were compared for 143 Candida sp. isolates to assess essential (within 2 log(2) dilutions) and categorical agreements (according to three susceptibility breakpoints). Based on agreement percentages, our data indicated that Etest is not suitable to test anidulafungin against Candida parapsilosis and C. guilliermondii (54.4 to 82.4% essential and categorical agreements) but is more suitable for C. albicans, C. glabrata, C. krusei, and C. tropicalis (87.9 to 100% categorical agreement).

We evaluated the performance of the 24-h broth microdilution voriconazole MIC by obtaining MICs for 2,162 clinical isolates of Candida spp. and other yeasts; the 24-h results were compared to 48-h reference MICs to assess essential, as well as categorical, agreement. Although the overall essential agreement was 88.6%, it ranged from 96.4 to 100% for 6 of the 11 species or groups of yeasts tested. The overall categorical agreement was 93.2%, and it was above 90% for eight species. However, unacceptable percentages of very major errors (false susceptibility) were observed for Candida albicans (2.7%), C. glabrata (4.1%), C. tropicalis (9.7%), and other less common yeast species (9.8%). Since it is essential to identify potentially resistant isolates and breakpoints are based on 48-h MICs, it appears that the 24-h MIC is not as clinically useful as the 48-h reference MIC. However, further characterization of these falsely susceptible MICs for three of the four common Candida spp. is needed to understand whether these errors are due to trailing misinterpretation or if the 48-h incubation is required to detect voriconazole resistance. Either in vivo versus in vitro correlations or the determination of resistance mechanisms should be investigated.

In order to update the epidemiological and mycological profile of candidaemia in Europe, the European Confederation of Medical Mycology conducted a prospective, sequential, hospital population-based study from September 1997 to December 1999. A total of 2,089 cases were documented by 106 institutions in seven European countries. Rates of candidaemia ranging from 0.20 to 0.38 per 1,000 admissions were reported. Candida albicans was identified in 56% of cases. Non-albicans Candida species were most frequently isolated from patients with haematological malignancies (65%). With increasing age, an increasing incidence of Candida glabrata was seen. The 30-day mortality rate was 37.9%. The survey results underline the burden of candidaemia in a wide range of patient populations, confirm the importance of non- albicans species, and provide baseline data for future surveillance studies at a European level.

An abstract of the article "Fungicidal Activity of Voriconazole Against Candida Krusei by Time-Kill Curves," by A. Espinel-Ingroff and colleagues is presented.