title: Clinical perspectives on echinocandin resistance among Candida species.
abstract: OBJECTIVE
  We review and offer our clinical perspectives on the emergence of echinocandin-resistant Candida.
  
  
  RESULTS
  Candida FKS gene mutations attenuate echinocandin activity, but overall mutation rates among clinical isolates remain low (Candida glabrata, ∼4%; other species, <1%). Rates are higher with prior echinocandin exposure, exceeding 50% among C. glabrata or Candida albicans isolates causing breakthrough invasive candidiasis. The median duration of prior echinocandin exposure among FKS mutant isolates is ∼100 days. The clinical usefulness of echinocandin susceptibility testing is limited by the low overall prevalence of resistance, and uncertainties surrounding testing methods and interpretation of minimum inhibitory concentrations (MICs). In single-center studies, caspofungin resistance (defined using institution-specific MIC breakpoints) was 32-53% sensitive and 75-95% specific for predicting treatment outcomes of C. glabrata invasive candidiasis; corresponding values for the presence of an FKS mutation were 35-41% and 90-98%. Results were similar using anidulafungin and micafungin MICs. Clinical data are scarce for non-C. glabrata species.
  
  
  CONCLUSIONS
  Echinocandins remain preferred agents against invasive Candida infections. Susceptibility testing and FKS genotypic testing do not have roles in routine clinical practice, but may be useful in newly-diagnosed patients who are echinocandin-experienced or those who have not responded to echinocandin treatment.
authors.affiliation: aDepartment of Medicine, University of Pittsburgh bVA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Shields
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002175:Candida / Q000187:drug effects* / Q000235:genetics; D002177:Candidiasis / Q000188:drug therapy* / Q000235:genetics; D058365:Candidiasis, Invasive / Q000188:drug therapy* / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D054714:Echinocandins / Q000494:pharmacology* / Q000627:therapeutic use; D005656:Fungal Proteins / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins