Antifungal susceptibility of 262 bloodstream yeast isolates from a mixed cancer and non-cancer patient population: is there a correlation between in-vitro resistance to fluconazole and the outcome of fungemia?

The aim of this study was to test the antifungal susceptibility of 262 bloodstream yeast isolates (164 Candida albicans strain, 88 non-albicans Candida spp. and 10 non-Candida yeasts) recovered from 169 surgical, neonatal, critically ill intensive care unit patients (ICU), and cancer patients (mixed patient population) to amphotericin B (AmB), fluconazole (FLU), 5-flucytosine (5-FC), itraconazole (ITRA), ketoconazole (KETO), miconazole (MICO), and nystatin (NYS), in order to correlate in-vitro resistance to fluconazole with the outcome of fungemia. The agar disk diffusion test was used to assess the susceptibility of the 262 bloodstream yeasts isolates. In addition, 78 strains isolated from cancer patients were also tested with the E-test. There were no differences in the susceptibility of the various C. albicans strains tested, except in 40 isolates from surgery patients, which showed a somewhat lower susceptibility to KETO and MICO to (3.7–5.5% resistance). There were no C. albicans strains resistant to AmB, NYS, or FLU. There were slight differences in the susceptibility patterns of the 88 non-albicans Candida spp. (NAC) isolates. Resistance to AmB and NYS appeared in 1 strain of C. guillermondii (minimum inhibitory concentration; MIC to AmB; 4 μg/ml) and in 1 strain of C. parapsilosis (MIC to NYS, 8 μg/ml and MIC to AmB, 2 μg/ml). All other NACs were susceptible to both polyenes (AmB and NYS). Nine of the 11 strains of C. krusei were resistant to FLU (MIC ≥ 64 μg/ml), the 2 exceptions showed, respectively, MICs for FLU of 6 and 32 μg/ml ("dose-dependent" susceptibility). However, only 2 of 29 C. glabrata strains were fully FLU-resistant (MIC ≥ 64 μg/ml), 27 being susceptible with MIC values of 0.5–8 μg/ml. Apart from 9 C. krusei and 2 C. glabrata strains, 2 C. parapsilosis strains and 1 strain of C. tropicalis were also FLU-resistant. Among the 88 NACs, 17.04% were FLU-resistant and 3.7% were KETO- and ITRA-resistant. Resistance to 5-FC and AmB was minimal. We compared the outcomes of patients infected with FLU-resistant vs FLU-susceptible yeasts in 161 evaluable patients treated with FLU. Attributable mortality was significantly higher (19.0% vs 8.6%; P < 0.01) in patients infected with the FLU-resistant yeasts.