Updated EUCAST Clinical Breakpoints against Aspergillus, Implications for the Clinical Microbiology Laboratory

Abstract

Azole resistance poses a problem for the management of patients with invasive aspergillosis. Former species are in fact groups of closely related species (or complexes); cryptic species frequently show high antifungal resistance. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) Definitive Document (E.Def) 9.3.2 includes guidelines for antifungal susceptibility testing on Aspergillus spp. and clinical breakpoints for amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole against A. flavus, A. fumigatus, A. nidulans, A. niger, and A. terreus. New clinical breakpoints were released in February 2020 and one of the most relevant modifications was the definition of the new “susceptible, increased exposure” (formerly “intermediate”) category. Another relevant change was the adoption of the concept of area of technical uncertainty (ATU) that refers to problematic areas which involve uncertainty of susceptibility categorisation (e.g., when minimum inhibitory concentrations (MICs) for susceptible and resistant organisms overlap). To accommodate both the new “susceptible, increased exposure” category and the concept of ATU, MICs of azoles and amphotericin B that fall in the former “intermediate” category have been automatically categorized as either R (amphotericin B) or ATU (triazoles). Finally, EUCAST-AFST (Antifungal Susceptibility Testing) decided to adopt new breakpoints for less common species provided that the epidemiological cut-off value (ECOFF) is below or comparable to the breakpoint for the type species (A. fumigatus).

First Investigative Study of Azole-Resistant Aspergillus fumigatus in the Environment in Burkina Faso

“…The MICs for voriconazole (MIC = 2 mg/L) fell under the area of technical uncertainty (ATU) suggested by the EUCAST committee in which voriconazole could be still used in clinical settings (non-invasive infections) if sufficient exposure is assured, but to our knowledge this is not performed in our screened region [15].…”

An expanded agar‐based screening method for azole‐resistant Aspergillus fumigatus

“…This new classification was designed as a warning to those problematics MICs overlapping the susceptible and resistant category. The uncertainty of this category gives an instruction to categorise and report the susceptibility based on the MICs to the other azoles tested 33 . [https://www.eucast.org/astoffungi/clinicalbreakpointsforantifungals/].…”

Mucormycosis in CAPA, a Possible Fungal Super-Infection

“…The commercial methods E-test (BioMèrieux) with RPMI-1640 medium (BioMèrieux) was used for the antifungal susceptibility. For Aspergillus spp., the EUCAST clinical breakpoint for fungi was employed [ 17 ]. No interpretative clinical breakpoints are available for Mucorales spp., and the classification of isolates as susceptible or resistant is not possible.…”