title: In vitro susceptibilities of zygomycetes to conventional and new antifungals.
abstract: In vitro susceptibilities of 36 zygomycete isolates, belonging to six genera, to itraconazole, posaconazole, voriconazole, terbinafine, amphotericin B and 5-fluorocytosine were determined by using a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M-38P reference method. The influence of incubation time on MIC values, and the performance of a spectrophotometric method for MIC determination in comparison with the visual reference method, were also evaluated. Amphotericin B was active against most of the isolates. All the isolates were highly resistant to 5-fluorocytosine (MICs > 256 mg/L). Voriconazole was significantly less active than the other drugs with an overall MIC(90) (MIC at which 90% of the isolates were inhibited) of 32 mg/L. In contrast, posaconazole showed good activity (MIC(90) 1 mg/L). A wide range of MICs, from 0.03 to > or =32 mg/L, was obtained for itraconazole and terbinafine. Differences in susceptibility between and within genera were noted. Rhizopus spp. were significantly less susceptible to itraconazole, posaconazole, terbinafine and amphotericin B than Absidia spp., and less susceptible than Mucor spp. to amphotericin B. Terbinafine appeared to be more active against Rhizopus microsporus than against Rhizopus oryzae (geometric mean MIC of 0.15 and 64 mg/L, respectively). The activity of the drugs was dependent on the incubation period. A significant increase in MICs was noted between 24 and 48 h of incubation. On the other hand, the two methods used for MIC determination (visual and spectrophotometric readings) showed good agreement. These results suggest that the zygomycetes are a heterogeneous group for antifungal susceptibility. Some of the conventional and new antifungals are effective in vitro; their efficacies in vivo remain to be determined. The spectrophotometric method appears to be a valuable alternative to the visual method for MIC determination for zygomycetes.
authors.affiliation: Department of Medical Microbiology, University Medical Center, St Radboud, PO Box 9101, 6500 HB Nijmegen.
authors.forename: Eric
authors.initials: E
authors.lastname: Dannaoui
authors.forename: Joseph
authors.initials: J
authors.lastname: Meletiadis
authors.forename: Johan W
authors.initials: JW
authors.lastname: Mouton
authors.forename: Jacques F G M
authors.initials: JF
authors.lastname: Meis
authors.forename: Paul E
authors.initials: PE
authors.lastname: Verweij
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D026141:Drug Resistance, Multiple, Fungal / Q000502:physiology*; D005658:Fungi / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D013053:Spectrophotometry / Q000379:methods
chemical_list: D000935:Antifungal Agents