Dannaoui Eric, Meletiadis Joseph, Mouton Johan W, Meis Jacques F G M, Verweij Paul E
Department of Medical Microbiology, University Medical Center, St Radboud, PO Box 9101, 6500 HB Nijmegen.
J Antimicrob Chemother. 2003 Jan;51(1):45-52. doi: 10.1093/jac/dkg020.
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.
采用美国国家临床实验室标准委员会M-38P参考方法的肉汤微量稀释法，测定了属于6个属的36株接合菌分离株对伊曲康唑、泊沙康唑、伏立康唑、特比萘芬、两性霉素B和5-氟胞嘧啶的体外敏感性。还评估了孵育时间对最低抑菌浓度（MIC）值的影响，以及与视觉参考方法相比，分光光度法测定MIC的性能。两性霉素B对大多数分离株有活性。所有分离株对5-氟胞嘧啶高度耐药（MIC>256mg/L）。伏立康唑的活性明显低于其他药物，总体MIC（90）（抑制90%分离株的MIC）为32mg/L。相比之下，泊沙康唑显示出良好的活性（MIC（90）为1mg/L）。伊曲康唑和特比萘芬的MIC范围很广，从0.03到≥32mg/L。注意到不同属之间和属内的敏感性差异。根霉属分离株对伊曲康唑、泊沙康唑、特比萘芬和两性霉素B的敏感性明显低于犁头霉属，对两性霉素B的敏感性低于毛霉属。特比萘芬对微小根霉的活性似乎比对米根霉更高（几何平均MIC分别为0.15和64mg/L）。药物的活性取决于孵育期。孵育24至48小时之间，MIC显著增加。另一方面，用于测定MIC的两种方法（视觉读数和分光光度读数）显示出良好的一致性。这些结果表明，接合菌在抗真菌药敏方面是一个异质群体。一些传统和新型抗真菌药物在体外有效；它们在体内的疗效仍有待确定。分光光度法似乎是用于测定接合菌MIC的视觉方法的一种有价值的替代方法。
