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Antimicrobial Agents and Chemotherapy, April 2004, p. 1197-1203, Vol. 48, No. 4
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.4.1197-1203.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Aspergillus fumigatus Variant with Decreased Susceptibility to Multiple Antifungals

S. Arunmozhi Balajee,1 Molly Weaver,1 Alexander Imhof,1 Jennifer Gribskov,1 and Kieren A. Marr1,2*

Program in Infectious Diseases, Fred Hutchinson Cancer Research Center,1 Department of Medicine, University of Washington, Seattle, Washington2

Received 30 June 2003/ Returned for modification 10 September 2003/ Accepted 9 December 2003

Isolates of Aspergillus fumigatus that demonstrate resistance to itraconazole (ITZ) have been described previously; however, the prevalence and clinical significance of ITZ resistance are not completely understood. In this study we assessed the ITZ susceptibilities of 128 A. fumigatus isolates that caused invasive infection in 82 stem cell transplant patients before and after the use of ITZ in our institution (study period, 1991 to 2000). The MICs for 10 isolates obtained from seven patients were high, >=1 µg/ml. The average ITZ MIC increased after institutional use of the drug began in 1995. The majority of the isolates for which MICs were high (6 of 10) and one isolate for which the MIC was low (0.06 µg/ml) demonstrated an unusual phenotype, appearing as predominantly white colonies. For all seven atypical isolates, voriconazole MICs were high (>=2 µg/ml), and minimal effective concentrations of caspofungin were high (>=4 µg/ml). For two of the seven atypical isolates, amphotericin B MICs were high (>=2 µg/ml). The isolates appeared white due to slow sporulation; however, after prolonged incubations, the isolates sporulated with no difference in conidial color or conidiophore morphology compared with typical isolates. Randomly amplified polymorphic DNA-PCR patterns of these isolates were distinct compared with those of other A. fumigatus isolates. Sequencing of 18S rRNA genes confirmed that all were A. fumigatus; however, the mitochondrial cytochrome b gene sequences of all the atypical isolates were unique. These data suggest the potential presence of a genetically unique, poorly sporulating variant of A. fumigatus that demonstrates decreased susceptibilities to several antifungals.

* Corresponding author. Mailing address: Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., D3-100, Seattle, WA 98109. Phone: (206) 667-6702. Fax: (206) 667-4411. E-mail: Kmarr{at}fhcrc.org.

Antimicrobial Agents and Chemotherapy, April 2004, p. 1197-1203, Vol. 48, No. 4
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.4.1197-1203.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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