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

oleh: Ali Korhan Sig, Meliha Cagla Sonmezer, Dolunay Gülmez, Serhat Duyan, Ömrüm Uzun, Sevtap Arikan-Akdagli

Format: Article
Diterbitkan: MDPI AG 2021-08-01

Deskripsi

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 <i>Candida</i> species including <i>Candida glabrata</i> 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 <i>FKS</i> mutant and phenotypically echinocandin-resistant <i>C. glabrata</i> 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 <i>C. glabrata</i> 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 <i>FKS2</i> 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 <i>C. glabrata</i> strains with high echinocandin MICs were isolated from the urine cultures of two unrelated patients from different wards with different mutations in <i>FKS2</i> 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 <i>C. glabrata</i>.