title: Activity of antifungal combinations against Aspergillus species evaluated by isothermal microcalorimetry.
abstract: We evaluated the activity of antifungals alone or in combination against Aspergillus fumigatus and Aspergillus terreus by real-time measurement of fungal growth-related heat production. Amphotericin B, voriconazole, caspofungin, and anidulafungin were tested alone or in combination. Heat production was measured in Sabouraud dextrose broth containing 10(5)Aspergillus conidia/mL for 48 h at 37 °C. Antifungal activity was evaluated by measuring the heat detection time relative to the growth control. Against A. fumigatus, the voriconazole-echinocandin combination demonstrated longer heat detection time than each antifungal alone. Against A. terreus, the combination amphotericin B-echinocandin prolonged the heat detection time, compared to each antifungal alone. In contrast, the echinocandin-voriconazole combination did not increase the heat detection time, compared to voriconazole alone. None of the antifungal combinations decreased the heat detection time compared to the antifungals alone (e.g. antagonism was not observed). Microcalorimetry has the potential for real-time evaluation of antifungal combinations against Aspergillus spp.
authors.affiliation: Department of Medicine, Infectious Diseases Service, Lausanne University Hospital, Lausanne, Switzerland. ulrika.furustrand@gmail.com
authors.forename: Ulrika
authors.initials: U
authors.lastname: Furustrand Tafin
authors.forename: Christina
authors.initials: C
authors.lastname: Orasch
authors.forename: Andrej
authors.initials: A
authors.lastname: Trampuz
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development; D002151:Calorimetry / Q000379:methods*; D004347:Drug Interactions; D006358:Hot Temperature; D008826:Microbial Sensitivity Tests / Q000379:methods
chemical_list: D000935:Antifungal Agents
keywords: Antifungals; Aspergillus spp.; Heat production; In vitro; Microcalorimetry