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

Abstract

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 0.25mg/l, 0.25mg/l, 0.5mg/l, and 0.06mg/l for fluconazole, amphotericin B, caspofungin, and micafungin, respectively. Fluconazole showed at least 50% fungal damage at ≥4mg/l (51.5%±6.63% to 78.38%±1.44%) and at ≥128mg/l (57.88%±9.2% to 67.25%±9.59%), while amphotericin B produced an even higher anti-biofilm effect at ≥0.5mg/l (64.63%±6.79% to 79.5%±5.9%) and at ≥0.12mg/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 ≥0.06mg/l (66.88%±10.16% to 98.63%±1.24%) and ≥0.25mg/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 0.015mg/l to 1mg/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 0.5mg/l (59.75%±3.16%) and at 0.06mg/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.