Combination antifungal therapy: the new frontier

The past decade has seen a significant increase in the incidence of invasive fungal infections. The antifungal armamentarium for the treatment of serious fungal infections remains limited. A possible approach to overcoming antifungal drug resistance and high mortality rates seen in severe fungal infections is to combine two or three classes of antifungals, especially if the drugs have different mechanisms of action. Combinations of new agents along with more traditional antifungals have now been shown to possess some synergistic or at least additive activity against many fungi in in vitro and animal studies. On the other hand, caution is still needed since some antifungal combinations have also demonstrated antagonistic activity. Well-controlled clinical trials are still required to define the most efficacious antifungal regimen. Furthermore, these trials should also evaluate the side-effect potential of combination regimens and the pharmacoeconomic impact these regimens may have.