Abstract
EUCAST has established clinical breakpoints for the six most common Candida species and Cryptococcus neoformans but not for less common yeasts because sufficient evidence is lacking. Consequently, the question “How to interpret the MIC?” for other yeasts often arises. We propose a pragmatic classification for amphotericin B, anidulafungin, fluconazole, and voriconazole MICs against 30 different rare yeasts. This classification takes advantage of MIC data for more than 4000 isolates generated in the EUCAST Development Laboratory for Fungi validated by alignment to published EUCAST MIC data. The classification relies on the following two important assumptions: first, that when isolates are genetically related, pathogenicity and intrinsic susceptibility patterns may be similar; and second, that even if species are not phylogenetically related, the rare yeasts will likely respond to therapy, provided the MIC is comparable to that against wild-type isolates of more prevalent susceptible species because rare yeasts are most likely “rare” due to a lower pathogenicity. In addition, the treatment recommendations available in the current guidelines based on the in vivo efficacy data and clinical experience are taken into consideration. Needless to say, it is of utmost importance (a) to ascertain that the species identification is correct (using MALDI-TOF or sequencing), and (b) to re-test the isolate once or twice to confirm that the MIC is representative for the isolate (because of the inherent variability in MIC determinations). We hope this pragmatic guidance is helpful until evidence-based EUCAST breakpoints can be formally established.
Highlights
The goal of in vitro antifungal susceptibility testing (AFST) according to the EUCAST (European Committee on Antimicrobial Susceptibility Testing) method is to inform the clinicians whether an antifungal drug is appropriate for an infection caused by a specific fungal isolate [1]
In most cases the breakpoint is the same value as the epidemiological cut-off values (ECOFFs) for susceptible species, either because the standard dose has been selected as the lowest dose that safely covers wild-type isolates or because sufficient evidence is not available to determine what degree of MIC elevation can occur without negatively affecting efficacy
C. guilliermondii (Meyerozyma guilliermondii) and C. fermentati (M. caribbica), which have even higher modal MICs of 0.5–1 mg/L, we found that the clinical data do not support any definitive recommendation regarding echinocandin monotherapy
Summary
The goal of in vitro antifungal susceptibility testing (AFST) according to the EUCAST (European Committee on Antimicrobial Susceptibility Testing) method is to inform the clinicians whether an antifungal drug is appropriate for an infection caused by a specific fungal isolate [1]. ESCMID and ECMM joint clinical guidelines were issued in 2014 for diagnosis and treatment of rare invasive yeast infections [13] and were recently revised as the global guideline as an initiative of ECMM in cooperation with ISHAM and ASM [14]. These guidelines do not include breakpoints for interpretation of individual MICs but do describe the level of evidence of clinical efficacy and recommended treatment. A list of current and previous yeast species names used in this document is available in Supplementary List S1
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