Species identification and in vitro antifungal susceptibility of aspergillus terreus species complex clinical isolates from a French multicenter study

Abstract

Aspergillus section Terrei is a species complex currently comprised of 14 cryptic species whose prevalence in clinical samples as well as antifungal susceptibility are poorly known. The aims of this study were to investigate A. Terrei clinical isolates at the species level and to perform antifungal susceptibility analyses by reference and commercial methods. Eighty-two clinical A. Terrei isolates were collected from 8 French university hospitals. Molecular identification was performed by sequencing parts of beta-tubulin and calmodulin genes. MICs or minimum effective concentrations (MECs) were determined for 8 antifungal drugs using both EUCAST broth microdilution (BMD) methods and concentration gradient strips (CGS). Among the 79 A. Terrei isolates, A. terreus stricto sensu (n 61), A. citrinoterreus (n 13), A. hortai (n 3), and A. alabamensis (n 2) were identified. All strains had MICs of 1 mg/liter for amphotericin B, except for two isolates (both A. hortai) that had MICs of 0.25 mg/liter. Four A. terreus isolates were resistant to at least one azole drug, including one with pan-azole resistance, yet no mutation in the CYP51A gene was found. All strains had low MECs for the three echinocandins. The essential agreements (EAs) between BMD and CGS were 90%, except for those of amphotericin B (79.7%) and itraconazole (73.4%). Isolates belonging to the A. section Terrei identified in clinical samples show wider species diversity beyond the known A. terreus sensu stricto. Azole resistance inside the section Terrei is uncommon and is not related to CYP51A mutations here. Finally, CGS is an interesting alternative for routine antifungal susceptibility testing.