Candida glabrata Resistance to Echinocandins Associated with FKS Genes Mutations: How Urgent is the Problem?

Clinical Microbiology and Antimicrobial Chemotherapy. 2016; 18(2):130-145

Journal article


The resistance of the systemic Candida infections causative agents is a cornerstone of the selection of an effective therapy. But if before the problem was limited to resistance to azole antifungals, then by now we have enough data about cases of treatment failures with echinocandins, which for today are the drugs of choice for treating most clinical form of invasive candidiasis. The largest number of reports connected to such problematic species as C. glabrata, frequency allocation is a steady tendency to growth, and which has a number of unique structural and functional features. The underlying mechanism of the development of resistance of Candida species in general, and C. glabrata in particular, are acquired, in most cases, after long-term therapy, mutations in the FKS1/FKS2 genes, which are responsible for the activity of the target for echinocandins –β-1,3-D-glucansynthase enzyme. The problems associated with the detection of such strains by conventional methods for determining the sensitivity, led in particular to the revision of interpretive criteria applied to existing protocols. Evidence to date information about the types of mutational changes could potentially help in the future in the development of genetic methods for detecting certain changes in the genes that can predict the likely ineffectiveness of echinocandins therapy. Identification of C. glabrata strains resistant to echinocandins is an important clinical problem in terms of the choice of therapy, and therefore we need to develop new approaches to therapy, including searching for new targets of action of drugs. In the absence of those now, the policy for antifungals use in the hospital should help to reduce unnecessary administration of echinocandins for therapeutic or prophylactic purposes — the main promoter of the emergence of resistant Candida strains.

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