title: Activity of voriconazole, itraconazole, fluconazole and amphotericin B in vitro against 1763 yeasts from 472 patients in the voriconazole phase III clinical studies.
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.
authors.affiliation: Health Protection Agency, Kingsdown, Bristol, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Johnson
authors.forename: Ana
authors.initials: A
authors.lastname: Espinel-Ingroff
authors.forename: Adrien
authors.initials: A
authors.lastname: Szekely
authors.forename: Hans
authors.initials: H
authors.lastname: Hockey
authors.forename: Peter
authors.initials: P
authors.lastname: Troke
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology* / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000382:microbiology; D017326:Clinical Trials, Phase III as Topic; D015725:Fluconazole / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology* / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use*; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D065819:Voriconazole; D015003:Yeasts / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D065819:Voriconazole