Journal Article

Progressive loss of echinocandin activity following prolonged use for treatment of <i>Candida albicans</i> oesophagitis

Michel Laverdière, Richard G. Lalonde, Jean-Guy Baril, Donald C. Sheppard, Steven Park and David S. Perlin

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 57, issue 4, pages 705-708
Published in print April 2006 | ISSN: 0305-7453
Published online February 2006 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkl022
Progressive loss of echinocandin activity following prolonged use for treatment of Candida albicans oesophagitis

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  • Medical Oncology
  • Critical Care

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Objectives: 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.

Keywords: micafungin; Candida infections; antifungal therapy; resistance to echinocandins; HIV infection

Journal Article.  2341 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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