JAC Advance Access originally published online on February 7, 2006
Journal of Antimicrobial Chemotherapy 2006 57(4):705-708; doi:10.1093/jac/dkl022
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Progressive loss of echinocandin activity following prolonged use for treatment of Candida albicans oesophagitis
1 Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; 2 McGill University Health Centre, Montreal, Quebec, Canada; 3 Clinique Médicale du Quartier Latin and Centre Hospitalier Universitaire de Montréal, Montreal, Quebec, Canada; 4 Public Health Research Institute, International Center for Public Health, Newark, NJ, USA
Received 5 October 2005; returned 15 December 2005; revised 19 December 2005; accepted 17 January 2006
* Corresponding author. Department of Microbiology—Infectious Disease, Hôpital Maisonneuve-Rosemont, 5415 boul de l'Assomption, Montreal, Quebec, Canada H1T 2M4. Tel: +1-514-252-3817; Fax: +1-514-252-3898; E-mail: laverdim{at}courrier.umontreal.ca
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
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