Treatment of invasive aspergillosis: Polyenes, echinocandins, or azoles?

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.