title: Successful treatment of Batrachochytrium salamandrivorans infections in salamanders requires synergy between voriconazole, polymyxin E and temperature.
abstract: Chytridiomycosis caused by the chytrid fungus Batrachochytrium salamandrivorans (Bsal) poses a serious threat to urodelan diversity worldwide. Antimycotic treatment of this disease using protocols developed for the related fungus Batrachochytrium dendrobatidis (Bd), results in therapeutic failure. Here, we reveal that this therapeutic failure is partly due to different minimum inhibitory concentrations (MICs) of antimycotics against Bsal and Bd. In vitro growth inhibition of Bsal occurs after exposure to voriconazole, polymyxin E, itraconazole and terbinafine but not to florfenicol. Synergistic effects between polymyxin E and voriconazole or itraconazole significantly decreased the combined MICs necessary to inhibit Bsal growth. Topical treatment of infected fire salamanders (Salamandra salamandra), with voriconazole or itraconazole alone (12.5 μg/ml and 0.6 μg/ml respectively) or in combination with polymyxin E (2000 IU/ml) at an ambient temperature of 15 °C during 10 days decreased fungal loads but did not clear Bsal infections. However, topical treatment of Bsal infected animals with a combination of polymyxin E (2000 IU/ml) and voriconazole (12.5 μg/ml) at an ambient temperature of 20 °C resulted in clearance of Bsal infections. This treatment protocol was validated in 12 fire salamanders infected with Bsal during a field outbreak and resulted in clearance of infection in all animals.
authors.affiliation: 1] Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium [2] Centre for Research and Conservation, Royal Zoological Society of Antwerp, Koningin Astridplein 26, 2018 Antwerp, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Blooi
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Pasmans
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Rouffaer
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Haesebrouck
authors.affiliation: Centre for Research and Conservation, Royal Zoological Society of Antwerp, Koningin Astridplein 26, 2018 Antwerp, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Vercammen
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Martel
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008411:Chytridiomycota / Q000187:drug effects*; D003091:Colistin / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy / Q000662:veterinary*; D013696:Temperature; D014562:Caudata / Q000382:microbiology; D065819:Voriconazole / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole; D003091:Colistin