Wayne State University, Detroit, MI, USA.
Diagn Microbiol Infect Dis. 2012 Jun;73(2):135-7. doi: 10.1016/j.diagmicrobio.2012.02.003.
We selected voriconazole-resistant (VCZ-R) Aspergillus fumigatus in the laboratory, characterized the cyp51A gene for possible mutations and evaluated the in vitro activities of voriconazole and anidulafungin alone and in combination against VCZ-R isolates of A. fumigatus using a fractional inhibitory concentration index (FICI) methodology. Voriconazole-resistant isolates were selected from wild-type A. fumigatus isolates in the laboratory by a 2-step selection process (plus 1 clinical isolate). The MICs of azoles (VCZ, posaconazole, itraconazole) and echinocandins (anidulafungin, micafungin, and caspofungin) for all A. fumigatus isolates were then determined in RPMI1640 using the broth microdilution technique recommended by the Clinical Laboratory and Standards Institute M38-A2 methodology and the FICI calculated. The combination of VCZ and anidulafungin was synergistic (FICI <0.5) not only against VCZ-susceptible isolates, but also against 8 of 10 VCZ-R, G448S mutants of A. fumigatus. The combination demonstrated synergy against the VCZ-R clinical isolate as well.
我们在实验室中选择了伏立康唑耐药（VCZ-R）烟曲霉，对可能的突变进行了 cyp51A 基因特征分析，并使用微量稀释法和棋盘微量稀释法测定了伏立康唑和安尼拉芬净单独及联合应用对 VCZ-R 烟曲霉分离株的体外活性（FICI）。采用两步筛选法（外加 1 例临床分离株），从实验室野生型烟曲霉分离株中筛选出 VCZ-R 分离株。使用临床实验室标准化研究所 M38-A2 方法推荐的 RPMI1640 肉汤微量稀释法测定所有烟曲霉分离株的唑类（伏立康唑、泊沙康唑、伊曲康唑）和棘白菌素类（安尼拉芬净、米卡芬净、卡泊芬净）的 MIC，并计算 FICI。伏立康唑和安尼拉芬净联合应用不仅对 VCZ 敏感的分离株具有协同作用（FICI<0.5），而且对烟曲霉 8 株中的 10 株 G448S 突变株也具有协同作用。该联合方案对 VCZ-R 临床分离株也表现出协同作用。
