In vitro interaction of terbinafine with itraconazole, fluconazole, amphotericin B and 5-flucytosine against Aspergillus spp

We investigated the in vitro interaction of terbinafine with itraconazole, fluconazole, amphotericin B and 5-flucytosine, against Aspergillus spp. We tested three isolates of Aspergillus fumigatus (one resistant to itraconazole), and two each of Aspergillus flavus, Aspergillus niger and Aspergillus...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2002-08, Vol.50 (2), p.189-194
Main Authors: Mosquera, J., Sharp, A., Moore, C. B., Warn, P. A., Denning, D. W.
Format: Article
Language:English
Subjects:
Amphotericin B - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal agents
Antifungal Agents - pharmacology
Aspergillus - drug effects
Aspergillus - isolation & purification
Biological and medical sciences
Drug Interactions
Drug Synergism
Drug Therapy, Combination
Fluconazole - pharmacology
Flucytosine - pharmacology
Humans
Itraconazole - pharmacology
Medical sciences
Microbial Sensitivity Tests - statistics & numerical data
Naphthalenes - pharmacology
Pharmacology. Drug treatments
Terbinafine
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Summary:We investigated the in vitro interaction of terbinafine with itraconazole, fluconazole, amphotericin B and 5-flucytosine, against Aspergillus spp. We tested three isolates of Aspergillus fumigatus (one resistant to itraconazole), and two each of Aspergillus flavus, Aspergillus niger and Aspergillus terreus. We employed a broth microdilution-based method derived from an in vivo validated method capable of detecting itraconazole resistance in A. fumigatus. We studied the effect on the MICs by calculation of the fractional inhibitory concentration (FIC) and fractional fungicidal concentration (FFC) (99.99% kill). Itraconazole and terbinafine were synergic or addit-ive in all strains (FIC = 0.15–1.0). Fluconazole and terbinafine were synergic with A. fumigatus, A. terreus and A. flavus (FIC = 0.3–0.5) and indifferent with A. niger (FIC = 2) isolates. Amphotericin B and terbinafine were mostly indifferent or antagonistic (FIC = 1.0–4.02). Flucytosine and terbinafine were usually indifferent or antagonistic (FIC = 0.63–8.5). FFCs were generally in accord with FICs. The use of terbinafine in combination therapy for Aspergillus infections with azoles seems promising, whereas terbinafine and amphotericin B or flucytosine in combination were less effective.
ISSN:0305-7453
1460-2091
1460-2091
DOI:10.1093/jac/dkf111