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Antimicrobial Agents and Chemotherapy, March 2009, p. 1185-1193, Vol. 53, No. 3
0066-4804/09/$08.00+0 doi:10.1128/AAC.01292-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Breakthrough Aspergillus fumigatus and Candida albicans Double Infection during Caspofungin Treatment: Laboratory Characteristics and Implication for Susceptibility Testing
Maiken Cavling Arendrup,1*
Guillermo Garcia-Effron,2
Walter Buzina,3
Klaus Leth Mortensen,1
Nanna Reiter,4
Christian Lundin,1
Henrik Elvang Jensen,5
Cornelia Lass-Flörl,6
David S. Perlin,2 and
Brita Bruun7
Unit of Mycology and Parasitology, Statens Serum Institut, Copenhagen, Denmark,1 Public Health Research Institute, New Jersey Medical School, UMDNJ, Newark, New Jersey,2 Institute of Hygiene, Microbiology, and Environmental Medicine, Medical University Graz, Graz, Austria,3 Department of Intensive Care Medicine, Roskilde Hospital, Roskilde, Denmark,4 Department of Disease Biology, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark,5 Department of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria,6 Department of Clinical Microbiology, Hillerød Hospital, Hillerød, Denmark7
Received 26 September 2008/ Returned for modification 24 November 2008/ Accepted 11 December 2008
Caspofungin is used for the treatment of acute invasive candidiasis and as salvage treatment for invasive aspergillosis. We report characteristics of isolates of Candida albicans and Aspergillus fumigatus detected in a patient with breakthrough infection complicating severe gastrointestinal surgery and evaluate the capability of susceptibility methods to identify candin resistance. The susceptibility of C. albicans to caspofungin and anidulafungin was investigated by Etest, microdilution (European Committee on Antibiotic Susceptibility Testing [EUCAST] and CLSI), disk diffusion, agar dilution, and FKS1 sequencing and in a mouse model. Tissue was examined by immunohistochemistry, PCR, and sequencing for the presence of A. fumigatus and resistance mutations. The MICs for the C. albicans isolate were as follows: >32 µg/ml caspofungin and 0.5 µg/ml anidulafungin by Etest, 2 µg/ml caspofungin and 0.125 µg/ml anidulafungin by EUCAST methods, and 1 µg/ml caspofungin and 0.5 µg/ml anidulafungin by CLSI methods. Sequencing of the FKS1 gene revealed a mutation leading to an S645P substitution. Caspofungin and anidulafungin failed to reduce kidney CFU counts in animals inoculated with this isolate (P > 0.05 compared to untreated control animals), while both candins completely sterilized the kidneys in animals infected with a control isolate. Disk diffusion and agar dilution methods clearly separated the two isolates. Immunohistochemistry and sequencing confirmed the presence of A. fumigatus without FSK1 resistance mutations in liver and lung tissues. Breakthrough disseminated aspergillosis and candidiasis developed despite an absence of characteristic FKS1 resistance mutations in the Aspergillus isolates. EUCAST and CLSI methodology did not separate the candin-resistant clinical isolate from the sensitive control isolate as well as did the Etest and agar methods.
* Corresponding author. Mailing address: Unit of Mycology and Parasitology (43/117), Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. Phone: 45 22 63 27 85. Fax: 45 3268 8180. E-mail: mad{at}ssi.dk
Published ahead of print on 22 December 2008.
Antimicrobial Agents and Chemotherapy, March 2009, p. 1185-1193, Vol. 53, No. 3
0066-4804/09/$08.00+0 doi:10.1128/AAC.01292-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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