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.