Nagy Fruzsina, Bozó Aliz, Tóth Zoltán, Daróczi Lajos, Majoros László, Kovács Renátó
Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Hungary.
Department of Solid State Physics, Faculty of Science and Technology, University of Debrecen, Hungary.
Med Mycol. 2018 Jun 1;56(4):493-500. doi: 10.1093/mmy/myx062.
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.
采用基于XTT的真菌损伤试验，测定了氟康唑、两性霉素B、卡泊芬净和米卡芬净对解脂耶氏酵母浮游细胞、早期和成熟生物被膜的活性。氟康唑、两性霉素B、卡泊芬净和米卡芬净对浮游细胞的MIC50分别为0.25mg/l、0.25mg/l、0.5mg/l和0.06mg/l。氟康唑在≥4mg/l（51.5%±6.63%至78.38%±1.44%）和≥128mg/l（57.88%±9.2%至67.25%±9.59%）时显示至少50%的真菌损伤，而两性霉素B在≥0.5mg/l（64.63%±6.79%至79.5%±5.9%）和≥0.12mg/l（77.63%±8.43%至92.75%±1.89%）时分别对早期和成熟生物被膜产生更高的抗生物被膜效果。对于米卡芬净，在≥0.06mg/l（66.88%±10.16%至98.63%±1.24%）和≥0.25mg/l（74.13%±10.77%至99.38%±0.38%）时分别观察到早期和成熟生物被膜有50%的真菌损伤。卡泊芬净处理的细胞呈现出意外的敏感性模式，即与生物被膜相比，浮游细胞在0.015mg/l至1mg/l浓度范围内敏感性显著降低（P<0.05 - 0.01）。在较高浓度下，浮游细胞和生物被膜的损伤相当。对于浮游细胞和生物被膜，分别在0.5mg/l（59.75%±3.16%）和0.06mg/l（70.25%±10.95%）时首次观察到50%的真菌损伤。使用扫描电子显微镜证实了这种意外模式。在较低卡泊芬净浓度下观察到的异常敏感性模式可能解释了在某些患者群体中卡泊芬净治疗解脂耶氏酵母感染效果较差。由于这种现象在米卡芬净的情况下明显不那么明显，这些数据表明米卡芬净可能是比卡泊芬净更可靠的治疗解脂耶氏酵母感染的选择。
