Combination Antifungal Therapy: When, Where, and Why

Combination antifungal therapy in the treatment of invasive fungal infections remains a controversial topic despite its increasing use based off case reports and series. There remains a paucity of well-controlled clinical studies to address which combination, the timing, and the benefits to the underlying host without causing toxicity. The evidence for using amphotericin B with 5 flucytosine for cryptococcal infections to reduce mortality has been effectively proven but the inaccessibility to 5 flucytosine requires the utilization of less effective combinations in many countries. For invasive aspergillosis, a large controlled clinical study in hematologic malignancy patients showed a trend for combination of voriconazole and anidulafungin to reduce mortality, especially in a subgroup of patients with positive galactomannan results. Outside of these two indications, the use of combination antifungal therapy in other patients and those with rare mold infections has not been proven and outcomes are heavily influenced by host factors rather than the combinations of antifungal treatment selected. © 2015, Springer International Publishing AG.