PATTERNS OF IN-VITRO ACTIVITY OF ITRACONAZOLE AND IMIDAZOLE ANTIFUNGAL AGENTS AGAINST CANDIDA-ALBICANS WITH DECREASED SUSCEPTIBILITY TO FLUCONAZOLE FROM SPAIN

Two groups of recent clinical isolates of Candida albicans consisting of 101 isolates for which fluconazole MICs were less than or equal to 0.5 mu g/ml (n = 50) and greater than or equal to 4.0 mu g/ml (n = 51) , respectively, were compared for their susceptibilities to fluconazol e, clotrimazole, miconazole, ketoconazole, and itraconazole. Susceptib ility tests were performed by a photometer-read broth microdilution me thod with an improved RPMI 1640 medium supplemented with 18 g of gluco se per liter (RPMI-2% glucose; J. L. Rodriguez-Tudela and J. V. Martin ez-Suarez, Antimicrob. Agents Chemother. 38:45-48, 1994). Preparation of drugs, basal medium, and inocula was done by the recommendations of the National Committee for Clinical Laboratory Standards. The MIC end point was calculated objectively from the turbidimetric data read at 2 4 h as the lowest drug concentration at which growth was just equal to or less than 20% of that in the positive control well (MIG 80%), In v itro susceptibility testing separated azole-susceptible strains from t he strains with decreased susceptibilities to azoles if wide ranges of concentrations (20 doubling dilutions) were used for ketoconazole, mi conazole, and clotrimazole. By comparison with isolates for which fluc onazole MICs were less than or equal to 0.5 mu g/ml, those isolates fo r which fluconazole MICs were greater than or equal to 4.0 mu g/ml wer e in general less susceptible to other azole drugs, but different patt erns of decreased susceptibility were found, including uniform increas es in the MICs of all azole derivatives, higher MICs of several azoles but not others, and elevated MICs of fluconazole only. On the other h and, decreased susceptibility to any other azole drug was never found among strains for which MICs of fluconazole were lower.