Ganesan L T, Manavathu E K, Cutright J L, Alangaden G J, Chandrasekar P H
Division of Infectious Diseases, Department of Medicine, Wayne State University, Detroit, MI 48201, USA.
Clin Microbiol Infect. 2004 Nov;10(11):961-6. doi: 10.1111/j.1469-0691.2004.00996.x.
The in-vitro activity of nikkomycin Z was investigated in combination with polyenes, triazoles or echinocandins against 20 clinical isolates of Aspergillus fumigatus with the fractional inhibitory concentration index (FICI) method. The drug interactions were classified as synergic (FICI < or = 0.5), no interaction (FICI > 0.5, but FICI < or = 4) or antagonistic (FICI > 4). The fungicidal activity of nikkomycin Z alone and in combination with a representative echinocandin (caspofungin) or triazole (voriconazole) was also examined with time-kill experiments and fungal cell viability assays. Two-drug combinations of nikkomycin Z with amphotericin B (FICI 3.59 +/- 0.57), amphotericin B lipid complex (FICI 3.95 +/- 0.74), liposomal amphotericin B (FICI 3.62 +/- 0.98), itraconazole (FICI 2.0 +/- 0.0), voriconazole (FICI 1.07 +/- 0.37), posaconazole (FICI 2.20 +/- 0.44) or ravuconazole (FICI 1.76 +/- 0.44) showed no interactions, but the pairwise combination of nikkomycin Z with caspofungin (FICI 0.22 +/- 0.19) or micafungin (FICI 0.35 +/- 0.27) showed synergic activity against A. fumigatus. Time-kill studies and fungal cell viability assays showed that neither nikkomycin Z nor caspofungin alone possessed fungicidal activity against A. fumigatus, whereas a combination of these two drugs at concentrations > or = 2 mg/L (> or = 0.031 x the concentration of drug that produced no visible growth) killed germinated conidia within 24 h in a concentration-dependent manner. These data suggest that two-drug combinations of nikkomycin Z with echinocandins, but not with polyenes and triazoles, have a synergic effect against A. fumigatus.
采用部分抑制浓度指数（FICI）法，研究了尼可霉素Z与多烯类、三唑类或棘白菌素类药物联合对20株烟曲霉临床分离株的体外活性。药物相互作用分为协同作用（FICI≤0.5）、无相互作用（FICI＞0.5但FICI≤4）或拮抗作用（FICI＞4）。还通过时间杀菌实验和真菌细胞活力测定，检测了尼可霉素Z单独以及与代表性棘白菌素（卡泊芬净）或三唑类（伏立康唑）联合使用时的杀真菌活性。尼可霉素Z与两性霉素B（FICI 3.59±0.57）、两性霉素B脂质复合物（FICI 3.95±0.74）、脂质体两性霉素B（FICI 3.62±0.98）、伊曲康唑（FICI 2.0±0.0）、伏立康唑（FICI 1.07±0.37）、泊沙康唑（FICI 2.20±0.44）或雷夫康唑（FICI 1.76±0.44）的两药联合未显示相互作用，但尼可霉素Z与卡泊芬净（FICI 0.22±0.19）或米卡芬净（FICI 0.35±0.27）的两两联合对烟曲霉显示出协同活性。时间杀菌研究和真菌细胞活力测定表明，尼可霉素Z和卡泊芬净单独对烟曲霉均无杀真菌活性，而这两种药物浓度≥2mg/L（≥产生无可见生长的药物浓度的0.031倍）的联合用药在24小时内以浓度依赖方式杀死了萌发的分生孢子。这些数据表明，尼可霉素Z与棘白菌素类药物的两药联合，而非与多烯类和三唑类药物联合，对烟曲霉具有协同作用。
