Echinocandin resistance

Abstract

Purpose of review Echinocandin resistance in Candida is a great concern, as the echinocandin drugs are recommended as 1st line therapy for patients with invasive candidiasis. Here we review recent advances in our understanding of the epidemiology, underlying mechanisms, methods for detection and clinical implications. Recent findings Echinocandin resistance has emerged over the recent years. It has been found in most clinically relevant Candida species, but is most common in C. glabrata with rates exceeding 10% at selected institutions. It is most commonly detected after 3–4 weeks of treatment and is associated with a dismal outcome. An extensive list of mutations in hot-spot regions of the genes encoding the target has been characterised and associated with species and drug specific loss of susceptibility. The updated antifungal susceptibility testing reference methods identify echinocandin resistant isolates reliably; while the performance of commercial tests is somewhat more variable. Alternative technologies are being developed including molecular detection and MALDI-TOF. Summary Echinocandin resistance is an increasingly encountered and mandates susceptibility testing particularly in patients with prior exposure. The further development of rapid and user-friendly commercially available susceptibility platforms is warranted. Antifungal stewardship is important in order to minimise unnecessary selection pressure.

CD101: a novel long‐acting echinocandin

“…While drug resistance has emerged with echinocandins over the last decade (Arendrup and Perlin, 2014), strategies to efficiently suppress the acquisition of resistance have not been successfully established. A key consideration to this dilemma is that it lacks proper measures of how to overcome development of resistant mutant subpopulations with antifungal drugs.…”

Rapid Detection and Identification of Candidemia by Direct Blood Culturing on Solid Medium by Use of Lysis-Centrifugation Method Combined with Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry (MALDI-TOF MS)

“…The prevalence of non-albicans Candida spp., particularly C. glabrata, and antifungal resistance have been increasing over time (16)(17)(18). The occurrence of resistant yeasts, including multidrug-resistant strains (19), renders the rapid identification and susceptibility testing of fungi isolated from blood essential (17). The availability of colonies on agar is a requirement for definitive testing.…”

“…While a Gram stain indicating yeast cells provides important information for the initiation of antifungal therapy, species identification and AST results are critical for the administration of appropriate targeted treatment (15). The prevalence of non-albicans Candida spp., particularly C. glabrata, and antifungal resistance have been increasing over time (16)(17)(18). The occurrence of resistant yeasts, including multidrug-resistant strains (19), renders the rapid identification and susceptibility testing of fungi isolated from blood essential (17).…”

Rapid Detection of FKS -Associated Echinocandin Resistance in Candida glabrata

“…The goal of current echinocandin breakpoints is to distinguish C. glabrata isolates with a WT FKS from those containing FKS mutations that are unlikely to respond to echinocandin therapy (9). While mutations at almost every amino acid position within the FKS hot spot 1 and 2 regions confer some degree of resistance (20), recent studies have shown that the majority of mutations that affect C. glabrata susceptibility to the echinocandins are located within FKS1 and FKS2 HS1 regions. Accordingly, these regions are the primary targets for molecular assays to detect drug resistance (6,21).…”