JAC Advance Access originally published online on January 25, 2008
Journal of Antimicrobial Chemotherapy 2008 61(3):616-620; doi:10.1093/jac/dkm518
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Original research |
Activities of voriconazole, itraconazole and amphotericin B in vitro against 590 moulds from 323 patients in the voriconazole Phase III clinical studies
1 Virginia Commonwealth University, Medical Centre, Richmond, VA, USA 2 Health Protection Agency, Myrtle Road, Kingsdown, Bristol, UK 3 Nevada Road, Hamilton 3216, New Zealand 4 The Old Court, Kingsgate, CT10 3LW Kent, UK
Received 3 October 2007; returned 26 November 2007; revised 9 November 2007; accepted 5 December 2007
* Corresponding author. Tel: +44-1843-863900; E-mail: peter2troke{at}btinternet.com
Introduction: Fungal pathogens from the voriconazole trials were identified and tested for susceptibility at two reference laboratories.
Methods: MICs were measured using CLSI M38-A 48 h microdilution methodology.
Results: Moulds from 29 genera and 38 species were isolated from 18 countries. Aspergillus spp. predominated (69%), followed by Scedosporium spp. (11.5%). Aspergillus fumigatus (292/590, 49.5%) was the most common species, followed by Scediosporium apiospermum (9.7%) and Aspergillus terreus (7.3%). The bronchi, lungs and sinuses yielded 45% of the isolates (57% of aspergilli), with 24% from the oropharynx/oesophagus. Other sites included blood/catheter (7.3%) and CNS (5.2%). MIC90s of itraconazole and voriconazole for Aspergillus spp. were the same (0.5 mg/L), but 17 Aspergillus isolates were itraconazole-resistant (MICs 
1–16 mg/L). Additionally, in 31 A. fumigatus and 23 A. terreus isolates, amphotericin MICs were 2.0 mg/L. Voriconazole MICs exceeded 4 mg/L in only 5.8% (34/590) of the isolates, including one A. fumigatus (8.0 mg/L), 9/11 Scedosporium prolificans, 10/13 Fusarium solani and all 9 Zygomycetes. Most were also not susceptible to itraconazole or amphotericin B. A notable increase in MIC (more than two doubling dilutions) during voriconazole therapy was seen for one A. fumigatus isolate. The response rate of voriconazole-treated patients with isolate MICs 4.0 mg/L was 38% when compared with 52% for those with MICs <4.0 mg/L.
Conclusions: Voriconazole shows activity, in vitro, similar to that of itraconazole against a wide range of moulds. It is also active against some isolates not susceptible to itraconazole or amphotericin B, but not the Zygomycetes. The relationship between voriconazole MIC and clinical outcome requires further study.
Keywords: Aspergillus , Scedosporium , Fusarium , Zygomycetes , MIC , clinical outcome
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