Clinical relevance of antifungal resistance

The availability of standard guidelines (NCCLS M27 document) for antifungal susceptibility testing has facilitated the establishment of tentative interpretive breakpoints for fluconazole and itraconazole by the NCCLS. Based on correlations of MIC values with the outcomes of patients with mostly Candida infections, fluconazole MICs of > or = 64 and itraconazole MICs of > or = 1.0 microgram/mL are considered resistant. Fluconazole MICs of 16 to 32 micrograms/mL and itraconazole MICs of 0.2 to 0.5 microgram/mL were categorized as "susceptible dependent upon dose" (S-DD), that is, clinical response may be obtained with increased doses. Susceptible breakpoints for fluconazole and itraconazole correspond to < or = 8 and < or = 0.12 microgram/mL, respectively. For flucytosine, resistant and susceptible breakpoints for Candida were set at > or = 32 micrograms/mL and 4 micrograms/mL, respectively, based on historical data and the drug's pharmacokinetics for Candida. Although no breakpoints have been established for amphotericin B, clinical failure has been associated with MICs > 1.0 microgram/mL.