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- Title
In vitro combinations of natamycin with voriconazole, itraconazole and micafungin against clinical Fusarium strains causing keratitis.
- Authors
Al-Hatmi, Abdullah M. S.; Meletiadis, Joseph; Curfs-Breuker, Ilse; Bonifaz, Alexandro; Meis, Jacques F.; De Hoog, G. Sybren
- Abstract
<bold>Objectives: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>The combination of natamycin with voriconazole was strongly synergistic at clinically achievable serum concentrations.
- Subjects
NATAMYCIN; VORICONAZOLE; FUSARIUM; TREATMENT of keratitis; ANTIFUNGAL agents; COMBINATION drug therapy; COMPARATIVE studies; DERMATOMYCOSES; DRUG interactions; DRUG synergism; FUNGI; KERATITIS; RESEARCH methodology; MEDICAL cooperation; MICROBIAL sensitivity tests; MYCOSES; PEPTIDES; RESEARCH; EVALUATION research; ITRACONAZOLE; PHARMACODYNAMICS
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2016, Vol 71, Issue 4, p953
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkv421