Activity of voriconazole, itraconazole, fluconazole and amphotericin B in vitro against 1763 yeasts from 472 patients in the voriconazole phase III clinical studies.
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.
Johnson
Elizabeth
E
Health Protection Agency, Kingsdown, Bristol, UK.
Espinel-Ingroff
Ana
A
Szekely
Adrien
A
Hockey
Hans
H
Troke
Peter
P
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*
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D065819:Voriconazole