MIC distributions for amphotericin B, fluconazole, itraconazole, voriconazole, flucytosine and anidulafungin and 35 uncommon pathogenic yeast species from the UK determined using the CLSI broth microdilution method

Abstract

Background Epidemiological cut-off values and clinical interpretive breakpoints have been developed for a number of antifungal agents with the most common Candida species that account for the majority of infections due to pathogenic yeasts species. However, less-common species, for which susceptibility data are limited, are increasingly reported in high-risk patients and breakthrough infections. Methods The UK National Mycology Reference Laboratory performs routine antifungal susceptibility testing of clinical yeast isolates submitted from across the UK. Between 2002 and 2016, >32 000 isolates representing 94 different yeast species were referred to the laboratory. Here we present antifungal susceptibility profiles generated over this period for amphotericin B, fluconazole, voriconazole, itraconazole, anidulafungin and flucytosine against 35 species of uncommon yeast using CLSI methodologies. MIC data were interpreted against epidemiological cut-off values and clinical breakpoints developed with Candida albicans, in order to identify species with unusually skewed MIC distributions that potentially indicate resistance. Results Potential resistance to at least one antifungal agent (>10% of isolates with MICs greater than the epidemiological cut-off or clinical breakpoint) was evidenced for 29/35 species examined here. Four species exhibited elevated MICs with all of the triazole antifungal drugs against which they were tested, and 21 species exhibited antifungal resistance to agents from at least two different classes of antifungal agent. Conclusions This study highlights a number of yeast species with unusual MIC distributions and provides data to aid clinicians in deciding which antifungal regimens may be appropriate when confronted with infections with rarer yeasts.

Name Changes for Fungi of Medical Importance, 2018 to 2019

“…In our laboratory, we have reported the identity of all clinical isolates using these revised names (including for the three species in the Nakaseomyces clade) since January 2019, together with a comment linking the novel names to the single most recent previous name listed in Table 3 (e.g., "isolate identified as Nakaseomyces glabrata, previously known as Candida glabrata"), without undue clinical confusion. We believe that this revised taxonomy that reflects phylogenetic relationships correlates better with unusual antifungal resistance profiles observed with many of the less common species of pathogenic yeasts (28,29). For example, the innate resistance of isolates of Pichia kudriavzevii (ex-Candida krusei) to fluconazole and flucytosine appears unusual compared with most other pathogenic "Candida" species but is a feature shared by many different Pichia species (28,29).…”

“…We believe that this revised taxonomy that reflects phylogenetic relationships correlates better with unusual antifungal resistance profiles observed with many of the less common species of pathogenic yeasts (28,29). For example, the innate resistance of isolates of Pichia kudriavzevii (ex-Candida krusei) to fluconazole and flucytosine appears unusual compared with most other pathogenic "Candida" species but is a feature shared by many different Pichia species (28,29). Thus, we believe that the practice of employing revised names for these pathogenic yeast species will be more informative to the clinician than persisting with the current misleading practice of using historical genera to group hundreds of genetically distantly related yeast species.…”

Antifungal Resistance among Less Prevalent Candida Non-albicans and Other Yeasts versus Established and under Development Agents: A Literature Review

“…MIC distribution dependent, the percentage of fluconazole mutants was higher (~11%) for C. glabrata [13,14,19]. Similar results were obtained for C. guilliermondii (2.4-8.4%), C. lusitaniae (9.2-12.7%), C. metapsilosis (3.3%) and C. orthopsilosis (4.4-10%), but overall lower for C. kefyr (1.9-5.6% [14,[18][19][20]25] (Table 2). High fluconazole modes also were reported for C. norvegensis [25,26].…”

“…Although the number of fluconazole MICs for C. albicans was substantial in most of the reports and by both methods, the MIC profiles were generally good with low modes/MIC 90 s as well as percentages of fluconazole mutants (0 to 5.6%, CLSI/EUC data) (Tables 1 and 2) [13,14,[18][19][20]22,25,26]. MIC distribution dependent, the percentage of fluconazole mutants was higher (~11%) for C. glabrata [13,14,19].…”

“…Although there are no CLSI BPs for this agent and any fungal pathogen, ECVs have been established by both reference methods for certain species [9,10] (Tables 1 and 2) [13][14][15][16][17][18][19][20][22][23][24]26]. In most instances, the highest MIC in the distribution is 1 µg/mL, with the exception of one distribution each of C. guilliermondii (0.03% NWT isolates) and C. lusitaniae (0% NWT) (Tables 1 and 2) [14,22,23,25]. As per the ECV definition, all these isolates will be considered WT.…”