Activity of voriconazole, itraconazole, fluconazole and amphotericin B in vitro against 1763 yeasts from 472 patients in the voriconazole phase III clinical studies

Elizabeth Johnson, Ana Espinel-Ingroff, Adrien Szekely, Hans Hockey, Peter Troke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

The susceptibility of 1763 yeast isolates (from 22 species and seven genera) was tested using Clinical and Laboratory Standards Institute M27-A2 microdilution methodology. Candida spp. predominated (97.1%), mainly C. albicans (51.4%), C. glabrata (16.4%) and C. tropicalis (13.7%), followed by Trichosporon spp. (1.1%) and Cryptococcus neoformans (1.0%). Most isolates came from blood/catheters (72.0%) or the oesophagus/oropharynx (11.3%). The voriconazole, itraconazole, fluconazole and amphotericin B MIC90 values (minimum inhibitory concentration for 90% of the isolates) for all isolates were 1.0, 2.0, 64 and 1.0 μg/mL, respectively. Voriconazole MICs correlated with those for fluconazole (r = 0.91) and itraconazole (r = 0.90). Only 109 isolates (6.2%) had voriconazole MICs ≥4.0 μg/mL; all were C. albicans, C. glabrata or C. tropicalis resistant to itraconazole (and most to fluconazole). Isolates from 22 patients with amphotericin MICs ≥2.0 μg/mL (range 2.0-16.0 μg/mL) were also cross-resistant to one or more of the triazoles. Patients (n = 34) with voriconazole-resistant isolates showed a 56% response to voriconazole therapy, and those patients (n = 261) with susceptible isolates showed a 71% response. Twenty-three voriconazole-treated patients had baseline resistant isolates, in eight patients voriconazole resistance developed during therapy and in three patients a different resistant species arose during therapy. Thus, voriconazole MICs correlate with those of fluconazole and itraconazole and may predict clinical outcome.

Original languageEnglish
Pages (from-to)511-514
Number of pages4
JournalInternational Journal of Antimicrobial Agents
Volume32
Issue number6
DOIs
Publication statusPublished - Dec 2008

Bibliographical note

Funding Information:
The data for this manuscript were generated during voriconazole phase III clinical trials sponsored by Pfizer Inc. Editorial support was provided by D. Wolf, MSc, at PAREXEL and was funded by Pfizer Inc.

Keywords

  • Candida
  • Clinical outcome
  • Cryptococcus
  • MIC
  • Trichosporon

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