title: Progressive loss of echinocandin activity following prolonged use for treatment of Candida albicans oesophagitis.
abstract: OBJECTIVE
  To illustrate the progressive loss of cross-echinocandin activity on Candida albicans isolates with strong clonal homology from a patient with advanced HIV infection and chronic oesophagitis progressively resistant to uninterrupted micafungin treatment.
  
  
  METHODS
  Antifungal susceptibility profiles for different antifungal agents were determined against serial C. albicans isolates retrieved before and during therapy. Multilocus sequencing typing (MLST) was performed on each of the isolates. FKS1 mutations conferring reduced susceptibility to echinocandin drugs were determined by DNA sequence analysis.
  
  
  RESULTS
  Four C. albicans isolates showing identical allelic homology were retrieved from the patient at the initiation and during therapy with micafungin. The progressive lack of clinical response to micafungin therapy was associated with increased MICs of all three echinocandin drugs (caspofungin, micafungin and anidulafungin) in association with the acquisition of mutations in the FKS1 gene.
  
  
  CONCLUSIONS
  This report documents for the first time a progressive loss of activity of all three echinocandin drugs against clonally related C. albicans isolates following long-term clinical exposure to this new class of antifungal agents.
authors.affiliation: Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada. laverdim@courrier.umontreal.ca
authors.forename: Michel
authors.initials: M
authors.lastname: Laverdière
authors.forename: Richard G
authors.initials: RG
authors.lastname: Lalonde
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Baril
authors.forename: Donald C
authors.initials: DC
authors.lastname: Sheppard
authors.forename: Steven
authors.initials: S
authors.lastname: Park
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000382:microbiology; D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D025141:Drug Resistance, Fungal / Q000235:genetics; D054714:Echinocandins; D004941:Esophagitis / Q000188:drug therapy* / Q000382:microbiology; D017809:Fatal Outcome; D005964:Glucosyltransferases / Q000235:genetics; D015658:HIV Infections / Q000150:complications; D006801:Humans; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D008565:Membrane Proteins; D010456:Peptides, Cyclic; D029701:Saccharomyces cerevisiae Proteins; D005964:Glucosyltransferases; C091618:FKS1 protein, S cerevisiae; D000077551:Micafungin