Invasive aspergillosis (IA) causes significant morbidity and mortality among immunocompromised hosts. Combination therapy with mold-active triazoles and echinocandins has been used with the hope of improving outcomes over monotherapy, especially in the setting of refractory disease. Herein, I update our prior systematic review and meta-analysis on combination therapy for salvage IA in the context of the recently published randomized clinical trial of combination therapy for primary IA. Clinicians should consider combination antifungals for IA in refractory disease despite immune reconstitution when there are concerns for resistance or pharmacokinetic variability.
The controversies surrounding the use of combination antifungal therapy for invasive aspergillosis (IA) are ongoing. Initially sparked by encouraging in vitro and animal studies that demonstrated synergistic or additive effects when combining a mold-active triazole (itraconazole, voriconazole, or posaconazole) or an amphotericin B with an echinocandin (caspofungin, micafungin, or anidulafungin), such as the neutropenia rabbit model of IA in which a correlation between in vitro synergy in plasma and fungal tissue burden decrease was noted, application to human clinical care in patients with IA became part of the approach to management in several small studies.