The Emergence of Echinocandin-Resistant Candida glabrata Exhibiting High MICs and Related FKS Mutations in Turkey

Abstract

The frequency of invasive fungal infections shows a rising trend as well as a high morbidity and mortality. Among the causative agents, a shift toward the non-albicans Candida species including Candida glabrata species complex is being observed in several centers. Echinocandin resistance is increasingly published; however, isolates presenting with an in vitro resistance have not yet been reported from Turkey. We, herein, report the first FKS mutant and phenotypically echinocandin-resistant C. glabrata clinical strains from a single center in Turkey. In a 43-year-old female patient, several enterocutaneous fistulae developed after a long term hospitalization period and several complicated surgeries. She eventually required parenteral nutrition via a tunneled central venous catheter (CVC). Following a number of bacteremic and fungemic episodes as well as intensive antimicrobial interventions (including fluconazole, caspofungin and anidulafungin), a CVC-related candidemia caused by C. glabrata was detected. The isolated strain yielded high minimum inhibitory concentration (MIC) values for echinocandins and was categorized as resistant. A resistance-related mutation was detected in FKS2 HS1 (D666V). Blood cultures remained negative after the removal of the CVC and treatment with caspofungin and high-dose fluconazole. Following this first case, two additional C. glabrata strains with high echinocandin MICs were isolated from the urine cultures of two unrelated patients from different wards with different mutations in FKS2 HS1 (S663P and delF659). Our findings indicate that routine antifungal susceptibility testing is crucial and underlines the need for attention for the increasing trend of acquired echinocandin resistance in C. glabrata.

Blinded Comparison in Identification of Yeasts: Conventional Methods vs Bd Phoenixtm

“…In the first multicenter candidemia study from Turkey, 7.7% of C. parapsilosis complex isolates were fluconazole resistant, while unexpectedly low fluconazole resistance was observed in C.glabrata complex isolates and there was no fluconazole-resistant isolate of C. tropicalis, along with absence of any echinocandin-resistant strain of any species (18). However, in 2021, Sig et al (19) from Turkey stated the first unfortunate news of C. glabrata complex isolates that showed both phenotypic and molecular echinocandin resistance. In addition, the recent spreading threat of C. auris has changed the general perspective substantially, since 93%, 35% and 7% of C. auris isolates are resistant to fluconazole, amphotericin B and echinocandins, respectively (4).…”

A multidimensional assessment of in-host fitness costs of drug resistance in the opportunistic fungal pathogenCandida glabrata

“…Candida (Nakaseomyces) glabrata is a major human fungal pathogen and the second leading cause of candidemia in many countries (11). C. glabrata rapidly develops resistance during antifungal treatment, with numerous studies reporting alarming increases in the prevalence of fluconazole-, echinocandin-, and multidrug-resistance (FLZR, ECR, and MDR, respectively) (12)(13)(14)(15)(16)(17). Fluconazole exerts fungistatic activity in Candida and targets Erg11, one of the critical proteins involved in ergosterol biosynthesis, whereas echinocandins (caspofungin, micafungin, and anidulafungin) are fungicidal and act by inhibiting the catalytic subunits of β-1,3-glucan synthase, Fks1 and Fks2.…”