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Clinical Microbiology Reviews, April 1998, p. 382-402, Vol. 11, No. 2
0893-8512/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance

Theodore C. White,1,2,* Kieren A. Marr,3,4 and Raleigh A. Bowden3,5

Department of Pathobiology, School of Public Health and Community Medicine,1 Department of Medicine,4 and Department of Pediatrics,5 University of Washington, Seattle Biomedical Research Institute,2 and Fred Hutchinson Cancer Research Center,3 Seattle, Washington

In the past decade, the frequency of diagnosed fungal infections has risen sharply due to several factors, including the increase in the number of immunosuppressed patients resulting from the AIDS epidemic and treatments during and after organ and bone marrow transplants. Linked with the increase in fungal infections is a recent increase in the frequency with which these infections are recalcitrant to standard antifungal therapy. This review summarizes the factors that contribute to antifungal drug resistance on three levels: (i) clinical factors that result in the inability to successfully treat refractory disease; (ii) cellular factors associated with a resistant fungal strain; and (iii) molecular factors that are ultimately responsible for the resistance phenotype in the cell. Many of the clinical factors that contribute to resistance are associated with the immune status of the patient, with the pharmacology of the drugs, or with the degree or type of fungal infection present. At a cellular level, antifungal drug resistance can be the result of replacement of a susceptible strain with a more resistant strain or species or the alteration of an endogenous strain (by mutation or gene expression) to a resistant phenotype. The molecular mechanisms of resistance that have been identified to date in Candida albicans include overexpression of two types of efflux pumps, overexpression or mutation of the target enzyme, and alteration of other enzymes in the same biosynthetic pathway as the target enzyme. Since the study of antifungal drug resistance is relatively new, other factors that may also contribute to resistance are discussed.

* Corresponding author. Mailing address: Seattle Biomedical Research Institute, 4 Nickerson St., Ste. 200, Seattle, WA 98109-1651. Phone: (206) 284-8846, ext. 344. Fax: (206) 284-0313. E-mail: tedwhite{at}u.washington.edu.

Clinical Microbiology Reviews, April 1998, p. 382-402, Vol. 11, No. 2
0893-8512/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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Copyright © 1998 by the American Society for Microbiology. All rights reserved.