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

Int J Antimicrob Agents. 2008 Dec;32(6):511-4. doi: 10.1016/j.ijantimicag.2008.05.023. Epub 2008 Sep 13.

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 microg/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 > or = 4.0 microg/mL; all were C. albicans, C. glabrata or C. tropicalis resistant to itraconazole (and most to fluconazole). Isolates from 22 patients with amphotericin MICs > or = 2.0 microg/mL (range 2.0-16.0 microg/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / pharmacology*
  • Amphotericin B / therapeutic use*
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use*
  • Candida / drug effects
  • Candidiasis / microbiology
  • Clinical Trials, Phase III as Topic
  • Fluconazole / pharmacology*
  • Fluconazole / therapeutic use*
  • Humans
  • Itraconazole / pharmacology*
  • Itraconazole / therapeutic use*
  • Microbial Sensitivity Tests
  • Mycoses / drug therapy*
  • Mycoses / microbiology*
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use*
  • Triazoles / pharmacology*
  • Triazoles / therapeutic use*
  • Voriconazole
  • Yeasts / drug effects*

Substances

  • Antifungal Agents
  • Pyrimidines
  • Triazoles
  • Itraconazole
  • Amphotericin B
  • Fluconazole
  • Voriconazole