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.
Highlights
Invasive fungal infections are observed more frequently due to an increased number of patients harboring major risk factors and, they have high mortality rates [1].The mortality rate of candidemia can vary according to the immune status, age and comorbidities of the host
The antifungal treatment was not revised as multiple follow-up blood cultures remained sterile after the central venous catheter (CVC) removal with the clearance of the infecting C. glabrata and C. albicans strains at day 5
More than a year after the isolation of the echinocandin-resistant strain from this first case, two additional C. glabrata strains (Strains No 2 and 3; Table 1) with high micafungin and anidulafungin minimum inhibitory concentration (MIC) were isolated from the urine cultures of two patients who were hospitalized in different wards located in different hospital buildings in our center
Summary
Invasive fungal infections are observed more frequently due to an increased number of patients harboring major risk factors and, they have high mortality rates [1].The mortality rate of candidemia can vary according to the immune status, age and comorbidities of the host. Echinocandin resistance in C. glabrata SC, defined as a determination of the minimum inhibitory concentration (MIC) values above the established breakpoints and accompanied by a demonstration of related FKS mutations in several studies, has been reported previously from many regions including Europe, Asia, Africa and the Americas [10,14]. These strains were in the susceptible (n = 1) or intermediate (n = 2) category when tested by the CLSI microdilution method for anidulafungin and micafungin and no in vitro echinocandin resistance could be detected [14,21].
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