J&P Medical Research Ltd., Vienna, Austria.
Pharmacology. 2011;88(3-4):213-24. doi: 10.1159/000331860. Epub 2011 Oct 6.
Invasive aspergillosis (IA) is a potentially lethal infection that affects mostly immunocompromised patients. The therapeutic goals are to restore leucocyte function and to reduce the fungal burden by effective antifungal agents and, contingently, by surgery. Several drugs for the treatment of IA are currently licensed. The longest known among them is amphotericin B (AmB). In well-performed clinical trials, approximately 30-50% of participants treated with AmB showed complete or partial response. However, this drug is associated with considerable acute and chronic toxicity which was somewhat mitigated by the development of lipid-based formulations. In contrast, voriconazole (VRC) is better tolerated, penetrates well into the central nervous system and may be given intravenously and orally in a sequential manner. The overall rates of favourable response to VRC were similar to that for AmB. Most notably, double-digit rates of complete remission were observed in studies including extraordinarily high proportions of patients with proven IA and specific risk factors. Disadvantages of VRC include the genetically determined interindividual variability of pharmacokinetics and the potential for drug-drug interactions that may require therapeutic drug monitoring. The recently introduced caspofungin (CPF) offers an excellent safety profile, but underperformed in terms of efficacy against mold infections. Other antifungals such as itraconazole and posaconazole are presently recommended as second-line option for the therapy or prophylaxis of (non-)IA. The value of micafungin and anidulafungin remains to be investigated in randomized clinical trials. In guidelines released by relevant medical societies, VRC is recommended as the first choice in the treatment of IA. AmB, preferably given as a liposomal preparation, or combinatory antifungal regimens combining VRC or liposomal AmB with CPF are stated as alternative options.
侵袭性曲霉病（IA）是一种潜在致命的感染，主要影响免疫功能低下的患者。治疗目标是通过有效的抗真菌药物恢复白细胞功能并降低真菌负荷，并在必要时通过手术。目前有几种治疗 IA 的药物获得了许可。其中最久的是两性霉素 B（AmB）。在表现良好的临床试验中，大约 30-50%用 AmB 治疗的参与者表现出完全或部分反应。然而，这种药物与相当大的急性和慢性毒性相关，这在一定程度上通过开发基于脂质的制剂得到缓解。相比之下，伏立康唑（VRC）的耐受性更好，能很好地渗透到中枢神经系统，并且可以静脉内和口服序贯给予。VRC 的总体有利反应率与 AmB 相似。最值得注意的是，在包括证明有 IA 和特定危险因素的患者比例极高的研究中，观察到完全缓解的双位数率。VRC 的缺点包括个体间药代动力学的遗传决定的变异性和药物相互作用的潜力，这可能需要治疗药物监测。最近推出的卡泊芬净（CPF）具有出色的安全性特征，但在针对霉菌感染的疗效方面表现不佳。其他抗真菌药物，如伊曲康唑和泊沙康唑，目前被推荐作为（非）IA 治疗或预防的二线选择。米卡芬净和阿尼芬净的价值仍有待在随机临床试验中进行研究。在相关医学协会发布的指南中，VRC 被推荐为治疗 IA 的首选药物。AmB，最好给予脂质体制剂，或联合抗真菌方案，将 VRC 或脂质体 AmB 与 CPF 联合使用，被列为替代选择。
