Combination therapy in treatment of experimental pulmonary aspergillosis: Synergistic interaction between an antifungal triazole and an echinocandin
Combination therapy in treatment of experimental pulmonary aspergillosis: Synergistic interaction between an antifungal triazole and an echinocandin
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DOI：
10.1086/375420
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发表时间：
2003-06-15
影响因子：
6.4
通讯作者：
Walsh, TJ
中科院分区：
文献类型：
--
作者：
Petraitis, V;Petraitiene, R;Walsh, TJ
侵袭性肺曲霉病是免疫功能低下患者发病和死亡的重要原因。同时抑制真菌细胞壁和细胞膜的生物合成可能会导致协同作用对烟曲霉。我们研究了米卡方净，一种新的棘白菌素，与雷康唑，第二代三唑，对实验性侵袭性肺曲霉病在持续性贫血兔的抗真菌活性。与单独使用任何一种药物相比，这种组合导致死亡率（P小于或等于0.001）、残余真菌负荷（P小于或等于0.05）和血清半乳甘露聚糖抗原血症（P小于或等于0.01）显著降低。联合治疗还导致有机体介导的肺损伤和胸部计算机断层扫描检测到的肺浸润减少（P小于或等于.05）（P小于或等于.001）。棘白菌素-三唑组合未观察到毒性。MTT菌丝损伤试验表明，三唑类抗真菌剂和棘白菌素之间存在显著的体外协同作用。抗真菌三唑和棘白菌素的组合可能代表了治疗侵袭性肺曲霉病的新策略。
Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Simultaneous inhibition of fungal cell-wall and cell-membrane biosynthesis may result in synergistic interaction against Aspergillus fumigatus. We studied the antifungal activity of micafangin, a new echinocandin, in combination with ravuconazole, a second-generation triazole, against experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. This combination led to significant reductions in mortality (P less than or equal to .001), residual fungal burden (P less than or equal to .05), and serum galactomannan antigenemia (P less than or equal to .01), compared with either agent alone. Combination therapy also resulted in reduction (P less than or equal to .05) of organism-mediated pulmonary injury and of pulmonary infiltrates detected by thoracic computed tomography (P less than or equal to .001). No toxicity was observed with the echinocandin-triazole combination. An MTT hyphal damage assay demonstrated significant in vitro synergistic interaction between the antifungal triazole and the echinocandin. The combination of an antifungal triazole and echinocandin may represent a new strategy for treatment of invasive pulmonary aspergillosis.