Emergence of novel mutations of caspofungin resistance in candida glabrata with prolonged therapy

Abstract

Background Resistance to echinocandin is rare but resistance emerging during therapy has been reported in the literature. In candida glabrata , mutations in the FKS1 and FKS2 regions of the glucan synthase complex has been reported. Two clinical isolates of candida glabrata from Queensland were noted to be caspofungin resistant after prolonged caspofungin therapy. Aim The aim of this study is to look at the resistance mutation in the candida glabrata isolates. Method The caspofungin minimum inhibitory concentration (MIC) for all isolates was confirmed using CLSI M27-A2 methodology. Isogenicity of the isolates was verified by multi-locus sequence typing (MLST). DNA was extracted from the isolates and the regions of interest of the glucan synthase enzyme complex were then sequenced against wild type sequences. Results The raised MIC to caspofungin of the clinical cases was confirmed. Isogenicity was verified with the presence of a persistent unique strain. Two novel mutations in the FKS2 glucan synthase enxyme complex were identified on sequencing, which has not been previously reported. Discussion Candidaemia by non- Candida albicans is increasing. Resistance to caspofungin may lead to treatment failure. It also leaves few alternatives for treatment of life-threatening candidiasis. Emerging resistance to caspofungin in C. glabrata , especially in cases of prolonged caspofungin exposure, creates the need for increased surveillance and heightened suspicion in the microbiology laboratory as well as in the clinical setting.