Echinocandin antifungal drug resistance in Candida species: a cause for concern?

The echinocandins, the newest generation of antifungal agents, are inhibitors of β-1,3-D-glucan synthesis, an action that damages fungal cell walls. Despite a relatively broad spectrum of activity, these drugs are rapidly fungicidal against most Candida spp and have established noninferiority over existing antifungal drugs in the treatment of invasive candidiasis. Clinical resistance to this class of agent is rare, although point mutations in the target Fksp have been shown to confer in vitro resistance to echinocandins in a range of Candida spp, which can result in clinical failures. In addition, the echinocandin treatment can induce a salvage mechanism involving the compensatory upregulation of chitin synthesis in the cell wall. Further elucidation of the echinocandin resistance mechanisms could be exploited to envisage new therapeutic strategies for the treatment of life-threatening Candida infections.