Echinocandin Resistance in Candida Species Isolates from Liver Transplant Recipients

Abstract

Liver transplant recipients are at risk of invasive fungal infections, especially candidiasis. Echinocandin is recommended as prophylactic treatment but is increasingly associated with resistance. Our aim was to assess echinocandin drug resistance in Candida spp. isolated from liver transplant recipients treated with this antifungal class. For this, all liver-transplanted patients in a University Hospital (Créteil, France) between January and June of 2013 and 2015 were included. Susceptibilities of Candida isolates to echinocandins were tested by Etest and the EUCAST reference method. Isolates were analyzed by FKS sequencing and genotyped based on microsatellites or multilocus sequence typing (MLST) profiles. Ninety-four patients were included, and 39 patients were colonized or infected and treated with echinocandin. Echinocandin resistance appeared in 3 (8%) of the treated patients within 1 month of treatment. One patient was colonized by resistant Candida glabrata, one by resistant Candida dubliniensis, and one by resistant Candida albicans Molecular analysis found three mutations in FKS2 HS1 (F659S, S663A, and D666E) for C. glabrata and one mutation in FKS1 HS1 (S645P) for C. dubliniensis and C. albicans Susceptible and resistant isolates belonged to the same genotype. To our knowledge, this is the first study on echinocandin resistance in Candida spp. in a liver transplant population. Most resistant isolates were found around/in digestive sites, perhaps due to lower diffusion of echinocandin in these sites. This work documents the risk of emergence of resistance to echinocandin, even after short-term treatment.

Keywords: Candida; Candida albicans; Candida dubliniensis; Candida glabrata; echinocandin; liver transplantation; resistance.

FIG 1

DNA sequencing chromatogram (A) and amino acid alignments (B) of the FKS2HS1 region in different C. glabrata isolates from patients. Lines 1, C. glabrata wild-type genome database sequence used for alignment (GenBank accession number XM_448401); lines 2, C. glabrata wild-type isolate; lines 3, F659S mutation found in resistant isolates from D12 to D61; lines 4, F659S and S663A mutations found in resistant isolates from D61 to D89; lines 5, F659S and D666E mutations found only in the D89 anus isolate. This isolate harbors another population with F659S and S663A mutations (lines 4).