Progressive loss of echinocandin activity following prolonged use for treatment of Candida albicans oesophagitis.
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.
Laverdière
Michel
M
Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada. laverdim@courrier.umontreal.ca
Lalonde
Richard G
RG
Baril
Jean-Guy
JG
Sheppard
Donald C
DC
Park
Steven
S
Perlin
David S
DS
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
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