Combination antifungal therapy for the treatment of invasive yeast and mold infections

Abstract

Combination antifungal therapy has been an area of great research and clinical interest since antifungals became available decades ago, in part driven by the severe morbidity and mortality associated with invasive fungal infections. Because of the availability of newer antifungal agents including echinocandins and expanded-spectrum triazoles, interest in combination antifungal therapy for invasive mold disease, especially invasive aspergillosis, has grown. This review examines combination antifungal therapy for the treatment of yeast and molds, including current studies evaluating combination antifungal therapy in three clinically important invasive fungal infections: candidiasis, cryptococcosis, and aspergillosis. This article focuses on recent clinical data and potential future clinical directions.

Sensitization of Candida albicans biofilms to various antifungal drugs by cyclosporine A

“…Combining azoles with flucytosine was found to result in either indifference or antagonism [11,12]. Also, combinations of AmB, azoles and echinocandin with azoles/ polyenes did not show significant antifungal activity [13]. Not many studies are available which have discussed efficacy of drug combinations against biofilm growth of C. albicans [14].…”

Treatment of invasive fungal diseases in cancer patients—Revised 2019 Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

“…The benefit of combination of D‐AmB plus 5‐flucytosine has not been substantiated by appropriate clinical trials 94,95 . There are limited data from uncontrolled trials with response rates of 42% for combinations of L‐AmB and caspofungin as primary or salvage therapy, 96 55% for combinations of caspofungin and polyenes or triazoles in cancer patients, 97 and a significantly reduced mortality rate for patients receiving caspofungin plus voriconazole vs voriconazole alone in refractory aspergillosis in a historically controlled trial among stem cell transplant recipients 98 .…”

An update on the pharmacoeconomics of antifungal pharmacotherapy

“…Each agent's mechanism of action and metabolism must be taken into consideration when choosing to combine antifungal drugs in order to prevent antagonism between the two drugs, drug-drug interactions, and severe toxicities. Unfortunately, there are limited data to establish the role of combination therapy in current practice aside from its use for the treatment of cryptococcal meningitis [52][53][54]. Furthermore, none of these papers have included a cost analysis of combination therapy.…”