Recent developments in antifungal susceptibility testing

Abstract

The evolution of new test methods in laboratory medicine often subscribes to a well worn aphorism: “necessity is the mother of invention.” Current information does not support routine testing of antifungal agents (14–16, 41). The future availability of several drugs with similar antifungal and pharmacological properties, such as triazoles, may offer the clinician a variety of nontoxic, effective therapies for systemic fungal disease. With a selection of agents to choose from, it is likely that clinicians will perceive a need for in vitro susceptibility data and the demand placed on laboratories for on-line testing will increase. The work of the NCCLS Subcommittee on Antifungal Susceptibility Testing indicates that standardization of in vitro sensitivity testing is possible and perhaps close at hand. Three remaining issues regarding in vitro testing should be mentioned. The first relates to the broth dilution method. The NCCLS Subcommittee recommends a modification of the broth macrodilution technique of Shadomy et al. (17) for yeast susceptibility testing (16, 24). However, most clinical microbiology laboratories are more familiar with the broth microdilution techniques used for antibacterial agents. Furthermore, advances in automation and instrumentation in this area have been geared toward microdilution methods. Antifungal testing by broth microdilution would probably be preferred by most laboratories, provided accuracy and reproducibility could be maintained. Recent evidence suggests this to be true (22, 31, 42, 43) but more data are needed. The second issue regards the expansion of antifungal susceptibility testing beyond isolates of Candida and Cryptococcus. Differences in growth rates and morphology (yeast versus mold), for example, would impact on inoculum preparation and length of incubation. The propensity and clinical significance of Candida and Cryptococcus species as agents of mycotic disease, however, justify them as initial targets for a standardized assay. A final consideration relates to the establishment of clinically relevant interpretive guidelines. With an available standardized method for antifungal testing it should be possible to approach the issue of interpretive guidelines according to proven NCCLS methods (44). Derivation of breakpoints should consider the distribution pattern of MICs for each drug-organism group, the clinical pharmacology of the antifungal agent, and clinical efficacy data (45). These measures are essential for producing a test that is not only accurate and reproducible, but also of medical relevance.