Case Report: Echinocandin-Resistance Candida glabrata FKS Mutants From Patient Following Radical Cystoprostatectomy Due to Muscle-Invasive Bladder Cancer

Abstract

Invasive Candida glabrata infections are not common complications after radical cystoprostatectomy. Furthermore, resistance to echinocandins arising during the course of a patient’s treatment is rarely recognised. We described a case of development of echinocandin resistance in a patient with muscle-invasive bladder cancer (pT2b N0 M0, high grade) diagnosis, subjected to radical cystoprostatectomy and exposed to echinocandins. A male patient with a previous surgical history after a traffic accident, who was operated on due to bladder cancer, underwent an episode of candidemia and mixed postoperative wound and urinary tract infection caused by C. glabrata and extended spectrum β-lactamase (ESBL)-producing Escherichia coli during hospital treatment. The patient was started on caspofungin. Repeat blood cultures showed clearance of the bloodstream infection; however, infection persisted at the surgical site. Resistance to echinocandins developed within 2 months from the day of initiation of therapy with caspofungin in the C. glabrata strain obtained from the surgical site. The isolates sequentially obtained during the patient’s treatment demonstrated resistance to echinocandins due to the mutation in hotspot 1 FKS2. Although resistance to echinocandins is relatively rare, it should be considered in oncological patients with increased complexity of treatment and intestinal surgery.

Reshaping Echinocandin Antifungal Drugs To Circumvent Glucan Synthase Point‐Mutation‐Mediated Resistance

“…To investigate if exposure of yeast to RZF‐1 versus rezafungin results in similar levels of echinocandin resistance, we used both echinocandins for adaptive laboratory evolution experiments [38] using C. glabrata strain 10, a clinical isolate, as a model. We chose strain 10 because it carries a deletion of phenylalanine 659 in Fks2p, a mutation frequently found in echinocandin‐resistant clinical isolates [31,39,40] . In strain 10, the RZF‐1 MIC 80 value was 8‐fold lower than the MIC 80 for rezafungin (Table S6).…”

Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis

“…This is consistent with the finding that none of the adaptors had mutations of FKS genes, since FKS mutations in clinical isolates of Candida spp. usually cause increased resistance to CSP (Balashov et al, 2006 ; Garcia-Effron et al, 2010 ; Imtiaz et al, 2012 ; Beyda et al, 2014 ; Marti-Carrizosa et al, 2015 ; Naicker et al, 2016 ; Szymankiewicz et al, 2021 ).…”

Reshaping Echinocandin Antifungal Drugs To Circumvent Glucan Synthase Point‐Mutation‐Mediated Resistance

“…We chose strain 10 because it carries a deletion of phenylalanine 659 in Fks2p, a mutation frequently found in echinocandin-resistant clinical isolates. [31,39,40] In strain 10, the RZF-1 MIC 80 value was 8fold lower than the MIC 80 for rezafungin (Table S6).…”