We report a case of Candida glabrata candidemia that developed resistance to micafungin within 8 days of initiation of therapy in a patient without previous echinocandin exposure or other known risk factors for clinical or microbiological failure. Pre-and postresistant isolates were confirmed to be isogenic, and sequencing of hot spots known to confer echinocandin resistance revealed a phenylalanine deletion at codon 659 within FKS2.
Echinocandins are now first-line agents for the treatment of invasive candidiasis (1-4). Their fungicidal activity, tolerability, perceived lack of resistance issues, and clinical superiority over fluconazole for candidemia have made them a cornerstone of anti-Candida therapy (5). However, there are increasing reports of Candida spp. becoming resistant to the echinocandins, usually in immunocompromised patients receiving prolonged therapy (6, 7). In addition, there is debate over the recent changes to the CLSI echinocandin breakpoints for Candida spp., which significantly lowered the threshold for resistance for many species, including Candida glabrata (8). We describe a case of rapid emergence of echinocandin resistance and clinical failure in a patient with C. glabrata fungemia who lacked the usual risk factors for echinocandin resistance (6, 9, 10).Case. A female patient in her mid-50s presented to the emergency department with acute pyelonephritis and persistent vomiting for the past 6 days. Her medical history was significant for a cerebrovascular accident 5 years previously, poorly controlled type 2 diabetes, and hypertension. Blood and urine cultures obtained in the emergency department grew Escherichia coli that was resistant to ciprofloxacin and trimethoprim-sulfamethoxazole. In the emergency department, her blood glucose was Ͼ500 mg/dl, she was treated for an anion gap metabolic acidosis, and she received vancomycin and piperacillin-tazobactam. She improved initially but was transferred to the medical intensive care unit (MICU) due to hypotension and respiratory failure requiring intubation. On hospital day (HD) 3, antibiotics were de-escalated to ceftriaxone when culture and susceptibility results returned. The patient developed acute kidney injury that required dialysis through a left femoral vein catheter but otherwise experienced a relatively uncomplicated ICU stay. On HD 11, she was transferred to the medical service, but on HD 13 she developed fever to 102.9°F and was restarted on vancomycin and piperacillin-tazobactam. No bacterial pathogens were isolated for the remainder of her hospital stay. The next day, fluconazole at 200 mg daily was initiated. On HD 15, blood cultures from HD 13 were positive for Candida sp., which was later identified as C. glabrata using the YST card with Vitek 2 and was susceptible-dose dependent (SDD) to fluconazole with an MIC of 16 g/ml and susceptible to micafungin, anidulafungin, and caspofungin with MICs of 0.015, 0.06, and 0.06 g/ml, respectively (Trek Sensititre YeastOne broth microdilution panel). On HD 15, fluconazole was discont...