In Vitro Activity of Antifungal Drugs against a Global Collection of 28 Clinical and Environmental Exserohilum Species Isolates

J. F. Meis, H. Madrid, I. Breuker, F. Hagen, G. S. De Hoog, A. Chowdhary

Author address: 

Canisius-Wilhelmina Hosp., Nijmegen, NETHERLANDS

Abstract: 

Background: Exserohilum species are common environmental moulds which have recently been implicated in a large outbreak of iatrogenic meningitis in the USA. Previously these moulds were rarely regarded as human pathogens therefore in vitro antifungal susceptibility data of these emerging moulds is scarce. Methods: A total of 28 clinical and environmental isolates of Exserohilum including 13 known species obtained from the CBS-KNAW Fungal Biodiversity Centre, Netherlands and VP Chest Institute, India were studied for in vitro susceptibility to antifungals according to CLSI guidelines. Identities of isolates were re-confirmed using AFLP fingerprinting and ITS sequencing. Results: Molecular identification revealed Exserohilum rostratum represented 28.5% (n=8) of isolates, and remaining species comprised one or two isolates of E. antillanum, E. gedarefense, E. heteropogonicola, E. holmii, E. curvatum, E. neoregeliae, E. pedicellatum, E. prolatum, and E. fusiforme. MIC90s of amphotericin B (0.5 μg/ml), posaconazole (0.5 μg/ml), and itraconazole (0.5 μg/ml) revealed excellent activity among all of the species. In contrast, higher MIC90s of voriconazole (2 μg/ml), isavuconazole (4 μg/ml ) and fluconazole(>64 μg/ml ) were observed. The echinocandins, micafungin and caspofungin showed similar MEC90s (2 μg /ml). E. rostratum MIC ranges were as follows: amphotericin B (0.063-1 μg/ml), posaconazole (0.125-0.5 μg/ml), itraconazole (0.125-0.5 μg/ml), voriconazole (0.5-2 μg/ml), isavuconazole (1-8 μg/ml ) and fluconazole(8->64 μg/ml ). E. holmii, E. curvatum and an unknown Exserohilum species (CBS 128064) had MICs of itraconazole of > 16 μg/ml and clustered together in the AFLP dendrogram. Conclusion: Amphotericin B, posaconazole and itraconazole had good in vitro activities against most Exserohilum species. Although variable azole MICs were observed depending on the species, voriconazole, the current drug of choice for therapy of Exserohilum rostratum meningitis showed acceptable in vitro activity. Study supported by Astellas Pharma and Merck, Sharpe and Dohme.
2013

abstract No: 

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Full conference title: 

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC, 53rd (2013)