Do Isolates with Borderline Resistant Micafungin MICs Always Harbor Hot Spot Mutations?

Antifungal susceptibility testing is important in guiding patient therapy due to an increasing number of resistant isolates. In the clinical strain collection of the Austrian resistance report (AURES), a high number of micafungin-resistant isolates (18.2% 49/269) was detected in seven different centres in Austria from 2011-2016. Most of these isolates showed a micafungin MIC value that was just above the clinical breakpoint (CB) established by EUCAST (0.016 mg/L). The aim of this study was to analyse whether strains showing a micafungin MIC value of 1-2 dilutions above the CB (0.032 mg/L and 0.064 mg/L) are associated with mutations in hotspot (HS) regions. 115 candidemia strains showing a micafungin MIC one or two dilutions above the EUCAST CB (0.032 mg/L and 0.064 mg/L) were categorized as borderline resistant and screened for mutations in HS1, HS2, and HS3 regions, which are known locations for the development of echinocandin resistance. For this purpose, we implemented targeted resequencing utilizing a next generation sequencing technology. No missense mutations could be detected in HS1, HS2, and HS3 in any of the 115 isolates, which indicated that resistance conferred by alteration of seems unlikely.