CLINICAL RELEVANCE OF ANTIFUNGAL RESISTANCE

The availability of standard guidelines (NCCLS M27 document) for antif ungal susceptibility testing has facilitated the establishment of tent ative Interpretive breakpoints for fluconazole and itraconazole by the NCCLS. Based on correlations of MIC values with the outcomes of patie nts with mostly Candida infections, fluconazole MICs of greater than o r equal to 64 and itraconazole MICs of greater than or equal to 1.0 mu g/mL are considered resistant. Fluconazole MICs of 16 to 32 mu g/mL a nd itraconazole MICs of 0.2 to 0.5 mu g/mL were categorized as ''susce ptible dependent upon dose'' (S-DD), that is, clinical response may be obtained with increased doses. Susceptible breakpoints for fluconazol e and itraconazole correspond to less than or equal to 8 and less than or equal to 0.12 mu g/mL, respectively. For flucytosine, resistant an d susceptible breakpoints for Candida were set at greater than or equa l to 32 mu g/mL and 4 mu g/mL, respectively, based on historical data and the drug's pharmacokinetics for Candida. Although no breakpoints h ave been established for amphotericin B, clinical failure has been ass ociated with MICs > 1.0 mu g/mL.