In vitro antifungal susceptibility patterns of planktonic and sessile Candida kefyr clinical isolates

The activity of fluconazole, amphotericin B, caspofungin and micafungin was determined using XTT-based fungal damage assays against planktonic cells, early and mature biofilms of Candida kefyr. Median MICs of planktonic cells were 0.25 mg/l, 0.25 mg/l, 0.5 mg/l, and 0.06 mg/l for fluconazole, amphotericin B, caspofungin, and micafungin, respectively. Fluconazole showed at least 50% fungal damage at ≥4 mg/l (51.5% ± 6.63% to 78.38% ± 1.44%) and at ≥128 mg/l (57.88% ± 9.2% to 67.25% ± 9.59%), while amphotericin B produced an even higher anti-biofilm effect at ≥0.5 mg/l (64.63% ± 6.79% to 79.5% ± 5.9%) and at ≥0.12 mg/l (77.63% ± 8.43% to 92.75% ± 1.89%) against early and mature biofilms, respectively. In case of micafungin, 50% fungal damage was observed at ≥0.06 mg/l (66.88% ± 10.16% to 98.63% ± 1.24%) and ≥0.25 mg/l (74.13% ± 10.77% to 99.38% ± 0.38%) for early and mature biofilms, respectively. Caspofungin-exposed cells showed an unexpected susceptibility pattern, that is, planktonic cells showed significantly decreased susceptibility at concentrations ranging from 0.015 mg/l to 1 mg/l compared to biofilms (P < .05-.01). The damage in planktonic cells and biofilms was comparable at higher concentrations. For planktonic cells and biofilms, 50% fungal damage was observed first at 0.5 mg/l (59.75% ± 3.16%) and at 0.06 mg/l (70.25% ± 10.95%), respectively. This unexpected pattern was confirmed using scanning electron microscopy. The unusual susceptibility pattern observed at lower caspofungin concentrations may explain the poorer outcome of caspofungin-treated C. kefyr infections documented in certain patient populations. As this phenomenon was markedly less apparent in case of micafungin, these data suggest that micafungin may be a more reliable option than caspofungin for the treatment of C. kefyr infections.