Schwartz S, Thiel E
Medizinische Klinik III, Charite Campus Benjamin Franklin, Berlin, Germany.
Med Mycol. 2009;47 Suppl 1:S387-93. doi: 10.1080/13693780802537953. Epub 2009 Feb 28.
Cerebral aspergillosis is increasingly recognized in severely immunocompromised patients and, until recently, this type of fungal infection was associated with a mortality approaching 100%. The central nervous system is a protected environment and penetration of drugs across the blood-brain barrier is mainly limited by their molecular size and physicochemical properties, as well as drug interaction with transporter systems (e.g., P-glycoprotein) at the blood-brain barrier. Most antifungal agents are large molecules (>700 Da), which makes sufficient penetration into the central nervous system unlikely. In fact, the available data indicate low levels of most antifungal agents in cerebrospinal fluid and brain tissue, except for fluconazole and voriconazole. Concentrations of voriconazole exceeding inhibitory concentrations for Aspergillus species were found repeatedly in cerebrospinal fluid and brain tissue, including brain abscess material. A recent retrospective study confirmed that voriconazole treatment resulted in improved response and survival rates in patients with cerebral aspergillosis. Data from animal models, which explored escalated doses or combinations of antifungal agents in experimental neuroaspergillosis, suggest that selected combination or dose-escalated therapies might further improve the still unsatisfactory prognosis in this particular type of Aspergillus infection.
在严重免疫功能低下的患者中，脑曲霉病越来越受到关注，直到最近，这种真菌感染的死亡率仍接近100%。中枢神经系统是一个受到保护的环境，药物穿过血脑屏障主要受其分子大小、理化性质以及药物与血脑屏障转运系统（如P-糖蛋白）相互作用的限制。大多数抗真菌药物是大分子（>700 Da），这使得它们不太可能充分渗透到中枢神经系统。事实上，现有数据表明，除氟康唑和伏立康唑外，大多数抗真菌药物在脑脊液和脑组织中的水平较低。在脑脊液和脑组织（包括脑脓肿材料）中反复发现伏立康唑的浓度超过了对曲霉菌的抑制浓度。最近一项回顾性研究证实，伏立康唑治疗可改善脑曲霉病患者的反应和生存率。动物模型的数据探索了在实验性神经曲霉病中增加抗真菌药物剂量或联合用药，结果表明，对于这种特殊类型的曲霉感染，选择联合用药或增加剂量的疗法可能会进一步改善仍不尽人意的预后。
