title: FKS mutant Candida glabrata: risk factors and outcomes in patients with candidemia.
abstract: BACKGROUND
  Echinocandins are recommended for Candia glabrata candidemia. Mutations in the FKS1 and FKS2 genes are associated with echinocandin resistance. Few studies have assessed risk factors for FKS mutant isolates and outcomes in patients receiving micafungin treatment.
  
  
  METHODS
  Patients with C. glabrata bloodstream infection admitted to a large, tertiary care hospital between 2009 and 2012 were included in this study. For each isolate, FKS1 and FKS2 genes were sequenced to identify mutations. Risk factors for FKS mutations and treatment outcomes in patients receiving an echinocandin were assessed using multivariate logistic regression.
  
  
  RESULTS
  Seventy-two patients were included in the study of which 13 (18%) had an FKS mutant isolate. The only significant predictor for FKS mutations was prior echinocandin exposure (odds ratio [OR], 19.9; 95% confidence interval [CI], 4.7-84.7; P ≤ .01). Treatment failure occurred in 17 (30%) of 57 patients who received an echinocandin and was more common in patients with FKS mutants (6 of 10; 60%) compared with non-FKS mutants (11 of 47; 23%). Underlying gastrointestinal disorder (OR, 4.7; 95% CI, 1.1-20.9; P = .04) and prior echinocandin exposure (OR, 8.3; 95% CI, 1.7-40.4; P ≤ .01) were independent predictors of echinocandin treatment failure. Treatment response and echinocandin minimum inhibitory concentrations varied among specific FKS mutations.
  
  
  CONCLUSIONS
  FKS mutations were identified in 18% of 72 patients with C. glabrata candidemia. Common risk factors for FKS mutant isolates included previous echinocandin exposure, which also influenced response rates.
authors.affiliation: Department of Clinical Sciences & Administration, University of Houston College of Pharmacy.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Beyda
authors.affiliation: Department of Clinical Sciences & Administration, University of Houston College of Pharmacy.
authors.forename: Julie
authors.initials: J
authors.lastname: John
authors.affiliation: Department of Clinical Sciences & Administration, University of Houston College of Pharmacy.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kilic
authors.affiliation: Department of Clinical Sciences & Administration, University of Houston College of Pharmacy.
authors.forename: Mohammad J
authors.initials: MJ
authors.lastname: Alam
authors.affiliation: Department of Microbiology, Baylor St. Luke's Medical Center, Houston, Texas.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Lasco
authors.affiliation: Department of Clinical Sciences & Administration, University of Houston College of Pharmacy.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Garey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use; D041221:Candida glabrata / Q000187:drug effects / Q000235:genetics*; D058387:Candidemia; D002177:Candidiasis / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*; D000077336:Caspofungin; D025141:Drug Resistance, Fungal / Q000235:genetics; D054714:Echinocandins / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005656:Fungal Proteins / Q000235:genetics*; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D063868:Patient Outcome Assessment; D011379:Prognosis; D012307:Risk Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D000077336:Caspofungin; D000077551:Micafungin
keywords: Candida glabrata; antifungal resistance; echinocandins; micafungin; systemic candidiasis