The role of combination antifungal therapy in the treatment of invasive aspergillosis: a systematic review

Abstract

Background: Because treatment outcomes of invasive aspergillosis (IA) remain suboptimal, clinicians have resorted to the use of combination antifungal therapy. We therefore sought to systematically review the evidence that addresses the role of combination antifungal therapy in the treatment of invasive aspergillosis.

Methods: We retrieved the literature from MEDLINE, EMBASE, Web of Science, Cochrane Controlled Trials Register, and Scopus from inception up to March 2011 for cohort and randomized controlled trial (RCT) studies that assessed the efficacy of combination antifungal therapy for IA and reported on clinical outcomes.

Results: Eight studies (one RCT and seven cohort studies) that enrolled a total of 1071 patients met our inclusion criteria. Six cohort studies examined the role of combination therapy for the primary treatment of IA and two for salvage therapy. Various antifungal combinations were used, mainly azoles with either an echinocandin or a polyene. Of the seven cohort studies, four reported adjusted effect estimates, one of which showed a better outcome with combination antifungal therapy and one a trend towards a better outcome, while the remaining two revealed that there was no added advantage of combination antifungal therapy over monotherapy or a better response with monotherapy, respectively. The randomized controlled trial revealed that the use of combination therapy was associated with a better outcome.

Conclusion: Cumulative evidence supporting the use of combination antifungal therapy in IA is conflicting and of moderate strength. Well-designed RCTs are required to adequately address the issue of the usefulness of this approach.