Emergence of resistant in Germany.

BACKGROUND

is the second leading fungal pathogen causing candidaemia and invasive candidiasis in Europe. This yeast is recognized for its rapid ability to acquire antifungal drug resistance.

OBJECTIVES

We systematically evaluated 176 isolates submitted to the German National Reference Center for Invasive Fungal Infections (NRZMyk) between 2015 and 2019 with regard to echinocandin and fluconazole susceptibility.

METHODS

Susceptibility testing was performed using a reference protocol (EUCAST) and a range of commercial assays. Hot spot regions of the echinocandin target genes were sequenced using Sanger sequencing.

RESULTS

In total, 84 of 176 isolates were initially classified as anidulafungin-resistant based on EUCAST testing. Of those, 71 harboured mutations in the glucan synthase encoding genes (13% in , 87% in 2). Significant differences in anidulafungin MICs were found between distinct mutation sites. 11 wild-type (WT) isolates initially classified as resistant exhibited anidulafungin MICs fluctuating around the interpretation breakpoint upon re-testing with multiple assays. Two WT isolates consistently showed high anidulafungin MICs and thus must be considered resistant despite the absence of target gene mutations. Over one-third of echinocandin-resistant strains displayed concomitant fluconazole resistance. Of those, isolates linked to bloodstream infection carrying a change at Ser-663 were associated with adverse clinical outcome.

CONCLUSIONS

Resistant strains are emerging in Germany. Phenotypic echinocandin testing can result in misclassification of susceptible strains. genotyping aids in detecting these strains, however, echinocandin resistance may occur despite a wild-type genotype.