Acquisition of flucytosine, azole, and caspofungin resistance in Candida glabrata bloodstream isolates serially obtained from a hematopoietic stem cell transplant recipient

Abstract

We describe the acquisition of flucytosine, azole, and caspofungin resistance in sequential Candida glabrata bloodstream isolates collected from a bone marrow transplant patient with clinical failure. Point mutations in C. glabrata FUR1 (CgFUR1) and CgFKS2 and overexpression of CgCDR1 and CgCDR2 were observed in resistant isolates.

FIG. 1.

Schematic representation of Candida glabrata bloodstream infection in an allogeneic HSCT recipient. Day 0 was the day of the first HSCT. The two HSCTs are represented with black arrows. Each plus symbol represents a C. glabrata-positive blood culture. Each isolate studied is indicated by a number. Dosages of antifungal drugs were as follows: FLC at 200 mg/day for the first two periods and 600 mg/day for the last period, 5FC at 150 mg/kg of body weight/day, LAMB at 3 mg/kg/day, CSF at 50 mg/day, and VRC at 300 mg/day.

FIG. 2.

Expression analysis of C. glabrata CgCDR1 and CgCDR2 genes in clinical isolates and in wild-type strain CBS138 (138). Northern blot analysis of total RNA from the clinical isolates 1, 2, 3, 4, and 5 and from strain CBS138 hybridized with CgCDR1 and CgCDR2 RNA probes. The ethidium bromide-stained 28S/18S rRNAs are shown as a control for loading.