JAC Advance Access originally published online on November 28, 2002
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Journal of Antimicrobial Chemotherapy (2003) 51, 45-52
© 2003 The British Society for Antimicrobial Chemotherapy
In vitro susceptibilities of zygomycetes to conventional and new antifungals
Departments of Medical Microbiology, 1 University Medical Center St Radboud, PO Box 9101, 6500 HB Nijmegen; 2 Canisius-Wilhelmina Hospital, PO Box 9015, 6500 GS, Nijmegen, The Netherlands
Received 5 November 2001; returned 4 June 2002; revised 1 July 2002; accepted 27 September 2002
In vitro susceptibilities of 36 zygomycete isolates, belonging to six genera, to itraconazole, posaconazole, voriconazole, terbinafine, amphotericin B and 5-fluorocytosine were determined by using a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M-38P reference method. The influence of incubation time on MIC values, and the performance of a spectrophotometric method for MIC determination in comparison with the visual reference method, were also evaluated. Amphotericin B was active against most of the isolates. All the isolates were highly resistant to 5-fluorocytosine (MICs > 256 mg/L). Voriconazole was significantly less active than the other drugs with an overall MIC90 (MIC at which 90% of the isolates were inhibited) of 32 mg/L. In contrast, posaconazole showed good activity (MIC90 1 mg/L). A wide range of MICs, from 0.03 to 
32 mg/L, was obtained for itraconazole and terbinafine. Differences in susceptibility between and within genera were noted. Rhizopus spp. were significantly less susceptible to itraconazole, posaconazole, terbinafine and amphotericin B than Absidia spp., and less susceptible than Mucor spp. to amphotericin B. Terbinafine appeared to be more active against Rhizopus microsporus than against Rhizopus oryzae (geometric mean MIC of 0.15 and 64 mg/L, respectively). The activity of the drugs was dependent on the incubation period. A significant increase in MICs was noted between 24 and 48 h of incubation. On the other hand, the two methods used for MIC determination (visual and spectrophotometric readings) showed good agreement. These results suggest that the zygomycetes are a heterogeneous group for antifungal susceptibility. Some of the conventional and new antifungals are effective in vitro; their efficacies in vivo remain to be determined. The spectrophotometric method appears to be a valuable alternative to the visual method for MIC determination for zygomycetes.
* Corresponding author. Tel: +31-24-361-43-56; Fax: +31-24-354-02-16; E-mail: p.verweij{at}mmb.azn.nl
Members of The Eurofung Network are listed in the Acknowledgements.
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