Antifungal susceptibility trend and analysis of resistance mechanism for Candida species isolated from bloodstream at a Japanese university hospital

Abstract

We compared the susceptibility of six commercially available antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin, micafungin, and amphotericin B) against 133 Candida bloodstream isolates between 2008 and 2013at Aichi Medical University Hospital. C.albicans was the most common isolate, followed by C.parapsilosis, C. glabrata, and C.tropicalis. MIC90s of voriconazole against C.albicans, C.parapsilosis, and C.tropicalis were the lowest and that of micafungin against C.glabrata was the lowest among the agents tested. Of the 133 isolates, two strains were identified as drug-resistant. One was a fluconazole-resistant C.glabrata strain, in which the ATP-binding cassette (ABC) transporter gene expression was upregulated. The other was a micafungin-resistant C.glabrata strain, that had 13 amino acid substitutions in FKS1 and FKS2, including a novel substitution V1342I in FKS1 hotspot 2. We also evaluated the susceptibility of T-2307, a novel class of antifungal agents used in clinical trials, against the fluconazole- and micafungin-resistant C.glabrata strain; the MICs of T-2307 were 0.0039 and 0.0078μg/mL, respectively. In conclusion, the incidence of bloodstream infection caused by drug-resistant Candida spp. was rare from 2008 to 2013at our hospital. Of 133 isolates, only two strains of C.glabrata were resistant to azoles or echinocandins, that upregulated the ABC transporter genes or had novel FKS mutations, respectively.