In vitro combinations of natamycin with voriconazole, itraconazole and micafungin against clinical Fusarium strains causing keratitis

Abdullah M S Al-Hatmi, Joseph Meletiadis, Ilse Curfs-Breuker, Alexandro Bonifaz, Jacques F Meis, G Sybren De Hoog

    Research output: Contribution to journal/periodicalArticleScientificpeer-review

    Abstract

    OBJECTIVES: Fusarium species cause a broad spectrum of infections, from superficial to disseminated disease. Because Fusarium species are intrinsically resistant to most antifungal drugs, new approaches are needed. The aim of the present study was to evaluate the in vitro combination of natamycin with currently used antifungal drugs.

    METHODS: The in vitro interactions of combinations between natamycin and voriconazole, itraconazole and micafungin applied to 20 clinical Fusarium strains (members of Fusarium falciforme, Fusarium napiforme, Fusarium petroliphilum, Fusarium proliferatum, Fusarium pseudensiforme and Fusarium sacchari) were evaluated using a chequerboard microdilution method. The MICs of all drugs alone and in combination were determined visually after 48 h and interactions were assessed using fractional inhibitory concentration index (FICI) analysis.

    RESULTS: MICs of voriconazole and natamycin alone were 4 to >16 and 4-8 mg/L, respectively. Values were reduced 3.5-10-fold to 0.02-0.5 mg/L and 0.5-5-fold to 0.13-2 mg/L in combination, for the currently used antifungals and natamycin, respectively, demonstrating additive to synergistic interactions. The combinations natamycin/voriconazole, natamycin/itraconazole and natamycin/micafungin were synergistic (FICI ≤0.5) for 70%, 15% and 5% of the strains, respectively. No antagonism was found.

    CONCLUSIONS: The combination of natamycin with voriconazole was strongly synergistic at clinically achievable serum concentrations.

    Original languageEnglish
    Pages (from-to)953-955
    Number of pages3
    JournalJournal of Antimicrobial Chemotherapy
    Volume71
    Issue number4
    DOIs
    Publication statusPublished - 24 Dec 2015

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