Patterson Thomas F
Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Med Mycol. 2006 Sep 1;44(Supplement_1):S357-S362. doi: 10.1080/13693780600826715.
Three classes of antifungals - the polyenes, the echinocandins, and the extended spectrum azoles - are now availabel for treating invasive aspergillosis (IA). New agents and formulations in these classes offer the possibility of decreased toxicity and improved outcomes. With the availability of newer antifungals, clinicians are challenged to understand the advantages and limitations of these new choices. Standard amphotericin B deoxycholate is associated with poor outcomes in addition to unacceptable toxicity and is no longer recommended as primary therapy for most patients. Lipid formulations of amphotericin reduce toxicity, but because of cost and toxicity concerns, they may not be used at optimal doses. Interestingly, a recent trial showed that initial use of higher doses of liposomal amphotericin at 10 mg kg-1 d-1 did not improve efficacy and was associated with more toxicity. Due to lack of complete killing or inhibition of Aspergillus, the echinocandins are not frequently used as primary therapy for aspergillosis, although their minimal toxicity and potential for combination therapy remains attractive. The newer triazoles, including voriconazole and posaconazole, offer fungicidal activity against Aspergillus and, for voriconazole, both intravenous as well as oral therapy. Voriconazole was compared with amphotericin B followed by other licensed therapy in a global trial that showed better outcomes and improved survival so that voriconazole is recommended as primary therapy for most patients with this disease. These studies also show that early, effective therapy is a key factor for a successful outcome. Consideration of risk for IA and early initiation of therapy may improve outcomes in this often lethal infection.
目前有三类抗真菌药物——多烯类、棘白菌素类和广谱唑类——可用于治疗侵袭性曲霉病（IA）。这些类别的新型药物和制剂有可能降低毒性并改善治疗效果。随着新型抗真菌药物的出现，临床医生面临着了解这些新选择的优势和局限性的挑战。标准的两性霉素B脱氧胆酸盐除了毒性不可接受外，治疗效果也不佳，不再推荐作为大多数患者的一线治疗药物。两性霉素的脂质制剂可降低毒性，但由于成本和毒性问题，可能无法以最佳剂量使用。有趣的是，最近一项试验表明，初始使用更高剂量的脂质体两性霉素，即10mg·kg-1·d-1，并没有提高疗效，反而增加了毒性。由于对曲霉菌缺乏完全杀灭或抑制作用，棘白菌素类药物虽然毒性极小且具有联合治疗的潜力，但并不常被用作曲霉病的一线治疗药物。新型三唑类药物，包括伏立康唑和泊沙康唑，对曲霉菌具有杀菌活性，对于伏立康唑，既有静脉注射剂型也有口服剂型。在一项全球试验中，将伏立康唑与两性霉素B及其他已获许可的治疗方法进行了比较，结果显示伏立康唑的治疗效果更好，生存率更高，因此推荐伏立康唑作为大多数患有这种疾病患者的一线治疗药物。这些研究还表明，早期、有效的治疗是取得成功治疗效果的关键因素。考虑IA的风险并尽早开始治疗可能会改善这种往往致命的感染的治疗效果。
