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Journal of Antimicrobial Chemotherapy (2002) 50, 189-194
© 2002 The British Society for Antimicrobial Chemotherapy

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

J. Mosquera1, A. Sharp1, C. B. Moore2, P. A. Warn1 and D. W. Denning1,3,*

1 School of Medicine, University of Manchester, Hope Hospital, Salford, Manchester M6 8HD; 2 Department of Microbiology, Salford Royal Hospital NHS Trust, Salford, Manchester M6 8HD; 3 Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK

Received 27 June 2001; returned 4 March 2002; revised 22 April 2002; accepted 12 May 2002

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.

* Correspondence address. Education and Research Centre, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK. Tel: +44-161-291-5811; Fax: +44-161-291-5806; E-mail: ddenning{at}man.ac.uk


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