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Successful treatment of Batrachochytrium salamandrivorans infections in salamanders requires synergy between voriconazole, polymyxin E and temperature

Mark Blooi (UGent) , Frank Pasmans (UGent) , Lieze Rouffaer (UGent) , Freddy Haesebrouck (UGent) , Francis Vercammen and An Martel (UGent)
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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 mu g/ml and 0.6 mu g/ml respectively) or in combination with polymyxin E (2000 IU/ml) at an ambient temperature of 15 degrees 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 mu g/ml) at an ambient temperature of 20 degrees 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.
Keywords
ITRACONAZOLE, COMBINATION, DENDROBATIDIS, TIME-KILL, AMPHOTERICIN-B, DISEASE, ANTAGONISM, CHYTRIDIOMYCOSIS, antimicrobial therapy, Infectious diseases, amphibians, AMPHIBIAN PATHOGEN, POPULATION DECLINES

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MLA
Blooi, Mark et al. “Successful Treatment of Batrachochytrium Salamandrivorans Infections in Salamanders Requires Synergy Between Voriconazole, Polymyxin E and Temperature.” SCIENTIFIC REPORTS 5 (2015): n. pag. Print.
APA
Blooi, M., Pasmans, F., Rouffaer, L., Haesebrouck, F., Vercammen, F., & Martel, A. (2015). Successful treatment of Batrachochytrium salamandrivorans infections in salamanders requires synergy between voriconazole, polymyxin E and temperature. SCIENTIFIC REPORTS, 5.
Chicago author-date
Blooi, Mark, Frank Pasmans, Lieze Rouffaer, Freddy Haesebrouck, Francis Vercammen, and An Martel. 2015. “Successful Treatment of Batrachochytrium Salamandrivorans Infections in Salamanders Requires Synergy Between Voriconazole, Polymyxin E and Temperature.” Scientific Reports 5.
Chicago author-date (all authors)
Blooi, Mark, Frank Pasmans, Lieze Rouffaer, Freddy Haesebrouck, Francis Vercammen, and An Martel. 2015. “Successful Treatment of Batrachochytrium Salamandrivorans Infections in Salamanders Requires Synergy Between Voriconazole, Polymyxin E and Temperature.” Scientific Reports 5.
Vancouver
1.
Blooi M, Pasmans F, Rouffaer L, Haesebrouck F, Vercammen F, Martel A. Successful treatment of Batrachochytrium salamandrivorans infections in salamanders requires synergy between voriconazole, polymyxin E and temperature. SCIENTIFIC REPORTS. 2015;5.
IEEE
[1]
M. Blooi, F. Pasmans, L. Rouffaer, F. Haesebrouck, F. Vercammen, and A. Martel, “Successful treatment of Batrachochytrium salamandrivorans infections in salamanders requires synergy between voriconazole, polymyxin E and temperature,” SCIENTIFIC REPORTS, vol. 5, 2015.
@article{6854155,
  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 mu g/ml and 0.6 mu g/ml respectively) or in combination with polymyxin E (2000 IU/ml) at an ambient temperature of 15 degrees 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 mu g/ml) at an ambient temperature of 20 degrees 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.},
  articleno    = {11788},
  author       = {Blooi, Mark and Pasmans, Frank and Rouffaer, Lieze and Haesebrouck, Freddy and Vercammen, Francis and Martel, An},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keywords     = {ITRACONAZOLE,COMBINATION,DENDROBATIDIS,TIME-KILL,AMPHOTERICIN-B,DISEASE,ANTAGONISM,CHYTRIDIOMYCOSIS,antimicrobial therapy,Infectious diseases,amphibians,AMPHIBIAN PATHOGEN,POPULATION DECLINES},
  language     = {eng},
  pages        = {8},
  title        = {Successful treatment of Batrachochytrium salamandrivorans infections in salamanders requires synergy between voriconazole, polymyxin E and temperature},
  url          = {http://dx.doi.org/10.1038/srep11788},
  volume       = {5},
  year         = {2015},
}

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