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JAC Advance Access published online on March 26, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn129
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Post-antifungal effect of amphotericin B and voriconazole against germinated Aspergillus fumigatus conidia

Erja Chryssanthou1,*, Alissha Loebig1 and Jan Sjölin2

1 Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden 2 Section of Infectious Diseases, Department of Medical Sciences, University Hospital, Uppsala, Sweden

Received 14 December 2007; returned 20 February 2008; revised 18 January 2008; accepted 4 March 2008

* Corresponding author. Tel: +46-851773566; Fax: +46-8308099; E-mail: erja.chryssanthou{at}karolinska.se

Objectives: The post-antifungal effect (PAFE) of amphotericin B and voriconazole on germinated Aspergillus fumigatus conidia was studied using the BacT/Alert detection system based on fungal CO2 production.

Methods: Germinated conidia of A. fumigatus were exposed to 1–10x MIC of amphotericin B for 1 and 4 h and to 2.5–40x MIC of voriconazole for 4 and 24 h. After removal of the drug by washing, similar numbers of exposed and control germlings were inoculated into Pedi-BacT culture bottles. CO2 production was automatically monitored until the bottles signalled positive. The difference in time for positive signals in drug-exposed and control bottles was used to calculate the PAFE.

Results: The killing rate of amphotericin B against germlings was both concentration- and time-dependent, as has been previously found for actively growing hyphae. Similarly, voriconazole showed fungicidal effect after 24 h of exposure, but not after 4 h. Amphotericin B induced a long concentration- and time-dependent PAFE, whereas voriconazole resulted in a short and dose-independent PAFE that was significantly longer after 24 h than after 4 h of exposure.

Conclusions: An automated method is presented for the determination of PAFE on filamentous fungi using quantifiable numbers of germinated conidia. In contrast to previous results obtained from conidia, this method could demonstrate a PAFE of amphotericin B on Aspergillus that shared characteristics similar to that on Candida spp.

Key Words: azoles , filamentous fungi , polyenes


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