Castaldo R A, Gump D W, McCormack J J
Antimicrob Agents Chemother. 1979 Jan;15(1):81-6. doi: 10.1128/AAC.15.1.81.
Forty recent clinical isolates of three different Candida sp. were tested in the microtiter system for susceptibility to two new 2,4-diaminoquinazoline (DAQ) compounds, amphotericin B and flucytosine. The two DAQ preparations showed activity similar to amphotericin B and flucytosine. The geometric mean minimal inhibitory concentrations for these four drugs were as follows: DAQ 1A, 0.64 mug/ml; DAQ 2A, 1.39 mug/ml; amphotericin B, 1.03 mug/ml; and flucytosine, 0.72 mug/ml. An additional seven DAQ compounds were tested but showed less or no activity against 17 Candida isolates. Forty-eight-hour viability studies with DAQ 2A alone or in combination with amphotericin B, flucytosine, or sulfamethoxazole were carried out with one isolate of intermediate susceptibility to each of these agents except sulfamethoxazole. For this isolate the combination of DAQ 2A and sulfamethoxazole was synergistic, and the combination of DAQ 2A and AMB was either synergistic or additive, whereas the combination of DAQ 2A and flucytosine was antagonistic. Although regrowth of cultures exposed to DAQ 2A was noted over a 48-h period, neither degradation of the drug nor development of resistance to the drug could be detected. Swiss white mice receiving DAQ 1A at a dose of 6 mg/kg for 5 days showed no obvious signs of toxicity, including weight loss.
对三种不同念珠菌属的40株近期临床分离株，在微量滴定系统中测试了它们对两种新型2,4 - 二氨基喹唑啉（DAQ）化合物、两性霉素B和氟胞嘧啶的敏感性。两种DAQ制剂显示出与两性霉素B和氟胞嘧啶相似的活性。这四种药物的几何平均最低抑菌浓度如下：DAQ 1A为0.64微克/毫升；DAQ 2A为1.39微克/毫升；两性霉素B为1.03微克/毫升；氟胞嘧啶为0.72微克/毫升。另外测试了七种DAQ化合物，但它们对17株念珠菌分离株的活性较低或无活性。对一株对除磺胺甲恶唑外的每种药物均呈中度敏感的分离株，单独使用DAQ 2A或与两性霉素B、氟胞嘧啶或磺胺甲恶唑联合进行了48小时生存力研究。对于该分离株，DAQ 2A与磺胺甲恶唑的联合具有协同作用，DAQ 2A与两性霉素B的联合要么具有协同作用要么具有相加作用，而DAQ 2A与氟胞嘧啶的联合具有拮抗作用。尽管在48小时内观察到暴露于DAQ 2A的培养物有再生长现象，但未检测到药物降解或对该药物的耐药性产生。接受剂量为6毫克/千克的DAQ 1A持续5天的瑞士小白鼠未表现出明显的毒性迹象，包括体重减轻。
