Antifungal Susceptibility Testing: Practical Aspects and Current Challenges

Authors: John H. Rex, Michael A. Pfaller, Thomas J. Walsh, Vishnu Chaturvedi, Ana Espinel-Ingroff, Mahmoud A. Ghannoum, Linda L. Gosey, Frank C. Odds, Michael G. Rinaldi, Daniel J. Sheehan, and David W. Warnock

Publication Year: 2001

PMID: 11585779

Antifungal susceptibility testing remains an area of intense interest. Susceptibility testing can be used for drug discovery and epidemiology, but this review will focus on use of antifungal susceptibility testing to predict therapeutic outcome. With the demonstration that susceptibility of Candida spp. to azole antifungal agents (particularly fluconazole) generated correlations with clinical outcome for some forms of candidiasis that were qualitatively similar to that seen for antibacterial agents (182) and the steady introduction of new drugs of both preexisting and new classes (9), the interest in and need for clinically relevant susceptibility testing has increased. The need extends beyond testing Candida spp. With resistance demonstrated among such diverse fungi as Cryptococcus neoformans (1, 150, 167, 185, 227), Aspergillus fumigatus (40, 47, 96, 104, 130), Aspergillus terreus (207, 216), Histoplasma capsulatum (224), Pseudallescheria boydii (Scedosporium apiospermum) (219), and Trichosporon spp. (217, 218), it is clear that the need for meaningful susceptibility test results is as great for the fungi as it is for the bacteria.

Although antifungal susceptibility testing remains less well developed and utilized than antibacterial testing, the scientific support for its validity has benefited greatly by extrapolation from antibacterial testing. Knowledge of mechanisms of antifungal resistance has been valuable in identifying resistant isolates and using them to validate in vitro measurement systems (75, 130, 213, 225). The application of the concepts of pharmacodynamics (W. A. Craig, Abstr. 36th Annu. Meet. Infect. Dis. Soc. Am., abstr. S67, 1998) to antifungal susceptibility testing (4–7; 23, 52, 54, 81, 85, 99, 100, 113; D. A. Andes, M. van Ogtrop, T. Stamsted, and B. Conklin, Abstr. 98th Gen. Meet. Am. Soc. Microbiol. 1998, abstr. F-88, 1998; E. J. Wolfe, M. E. Klepser, and M. A. Pfaller, Abstr. 34th Annu. Meet. Infect. Dis. Soc. Am., abstr. 76, 1996) has provided significant new insights into both the methods for and interpretation of antifungal susceptibility testing. In addition, novel techniques for susceptibility testing provide useful additional tools and insights. It is the purpose of this review to summarize developments in this area since the last major reviews on this topic (59, 67, 74, 160, 183). This paper is not an exhaustive review of all prior work in this area, and it will focus on the issues that are important to testing in the clinical laboratory with special emphasis on the well-studied National Committee for Clinical Laboratory Standards (NCCLS) methodologies. For additional background information, the interested reader is referred to these reviews for additional data.

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