POSITIVE INTERACTION OF NIKKOMYCINS AND AZOLES AGAINST CANDIDA-ALBICANS INVITRO AND INVIVO
POSITIVE INTERACTION OF NIKKOMYCINS AND AZOLES AGAINST CANDIDA-ALBICANS INVITRO AND INVIVO
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DOI：
10.1128/aac.36.6.1284
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发表时间：
1992-06-01
影响因子：
4.9
通讯作者：
SCHALLER, K
中科院分区：
文献类型：
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作者：
HECTOR, RF;SCHALLER, K
真菌几丁质合成酶的竞争性抑制剂尼克霉素X和Z（NZ）与唑类化合物在一系列体外棋盘测定中组合以测试对念珠菌属的协同作用。尼可霉素和唑类的所有组合测试导致显着的协同活性对分离的白色念珠菌，分数抑制浓度指数范围从0.016到0.28。与C. tropicalis、热带假丝酵母C. parapsilosis或C. krusei，尽管后两者的结果表明存在累加效应。在小鼠静脉感染C.白色念珠菌，NZ以5至50 mg/kg体重的剂量范围每天两次单独给药能够延迟死亡的发生，但没有显示出剂量-反应效应。以8：1至40：1或更大的比例（wt/wt）口服NZ和唑类R 3783的组合比单独给予药物更能提高生存率，但这种效果在涉及氟康唑的组合中不太明显。在静脉感染C.的远交小鼠的短期器官负荷试验中。白色念珠菌，NZ与R 3783的高比例降低肾脏中每克CFU比单独药物更显著。在对念珠菌病更敏感的远交系小鼠或近交系小鼠中，使用NZ和氟康唑组合的短期真菌负荷测定未观察到统计学显著降低。在大鼠阴道念珠菌病模型中，口服或阴道给药的NZ和R 3783的组合比单独使用药物更有效。因此，在某些条件下，尼可霉素和选择唑类的联合治疗可能会增加念珠菌病的治疗效果。
Nikkomycins X and Z (NZ), competitive inhibitors of fungal chitin synthetase, were combined with azoles in a series of in vitro checkerboard assays to test for synergism against Candida spp. All combinations of nikkomycins and azoles tested resulted in marked synergistic activity against an isolate of Candida albicans, with fractional inhibitory concentration indices ranging from 0.016 to 0.28. No synergistic effect was demonstrable with isolates of C. tropicalis, C. parapsilosis, or C. krusei, though results for the latter two were suggestive of an additive effect. In survival models of mice infected intravenously with C. albicans, NZ administered singly in doses ranging from 5 to 50 mg/kg of body weight twice a day was able to delay the onset of mortality but showed no dose-response effect. The combination of NZ and the azole R 3783 administered orally in a ratio of 8:1 to 40:1 or greater (wt/wt) enhanced survival better than did the drugs given individually, but this effect was less evident for combinations involving fluconazole. In short-term organ load assays with outbred mice infected intravenously with C. albicans, high ratios of NZ to R 3783 reduced the CFU per gram in kidneys more significantly than did the drugs individually. Statistically significant reductions were not seen for short-term fungal burden assays using combinations of NZ and fluconazole in outbred mice or in inbred mice more susceptible to candidiasis. In a model of rat vaginal candidiasis, the combination of NZ and R 3783 administered either orally or vaginally was more effective than the drugs used singly. Thus, under certain conditions, combination therapy with nikkomycin and select azoles may offer promise for an increased therapeutic effect in candidiasis.