Manavathu E K, Cutright J L, Loebenberg D, Chandrasekar P H
Division of Infectious Diseases, Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
J Antimicrob Chemother. 2000 Aug;46(2):229-34. doi: 10.1093/jac/46.2.229.
We investigated the in vitro susceptibilities of clinical and laboratory-selected Aspergillus spp. to posaconazole, and compared the results with those obtained for amphotericin B, itraconazole and voriconazole. Conidial suspensions from clinical isolates (284 Aspergillus fumigatus, 66 Aspergillus niger, 31 Aspergillus flavus and 43 Aspergillus spp.) and laboratory-selected resistant A. fumigatus isolates (15 resistant to amphotericin B, 25 to itraconazole and 12 to voriconazole) were prepared and their susceptibilities to various antifungal agents determined using a previously described broth macrodilution technique. The geometric mean MICs (mg/L) of posaconazole for A. fumigatus (0.17 +/- 0.11) and non-A. fumigatus aspergilli (0.16 +/- 0.28) were significantly lower (P 0.05) than those for amphotericin B, itraconazole and voriconazole. Amphotericin B-resistant A. fumigatus isolates were as susceptible to posaconazole as the parental strain. Itraconazole- and voriconazole-resistant isolates showed low-level (two- to three-fold increase in MICs) cross-resistance to posaconazole. The minimum fungicidal concentrations (mg/L) of posaconazole for A. fumigatus (n = 58) and non-A. fumigatus aspergilli (n = 40) were 4. 45 +/- 2.70 (range 0.25-8) and 4.14 +/- 3.03 (range 0.5-8), respectively. Time-kill studies showed that the fungicidal activity of posaconazole against A. fumigatus is time- and concentration-dependent (for example, posaconazole 4 mg/L killed >99% of A. fumigatus conidia within 24 h). These results suggest that overall, posaconazole has better activity and a smaller range of MICs for Aspergillus spp., including those with reduced susceptibility to amphotericin B, itraconazole and voriconazole.
我们研究了临床和实验室筛选的曲霉菌株对泊沙康唑的体外敏感性，并将结果与两性霉素B、伊曲康唑和伏立康唑的结果进行比较。制备了临床分离株（284株烟曲霉、66株黑曲霉、31株黄曲霉和43株其他曲霉菌株）以及实验室筛选的耐烟曲霉分离株（15株对两性霉素B耐药、25株对伊曲康唑耐药和12株对伏立康唑耐药）的分生孢子悬液，并使用先前描述的肉汤稀释技术测定它们对各种抗真菌药物的敏感性。泊沙康唑对烟曲霉（0.17±0.11）和非烟曲霉曲霉菌（0.16±0.28）的几何平均MIC（mg/L）显著低于（P<0.05）两性霉素B、伊曲康唑和伏立康唑。耐两性霉素B的烟曲霉分离株对泊沙康唑的敏感性与亲本菌株相同。耐伊曲康唑和伏立康唑的分离株对泊沙康唑表现出低水平（MIC增加两到三倍）的交叉耐药性。泊沙康唑对烟曲霉（n = 58）和非烟曲霉曲霉菌（n = 40）的最低杀菌浓度（mg/L）分别为4.45±2.70（范围0.25 - 8）和4.14±3.03（范围0.5 - 8）。时间杀菌研究表明，泊沙康唑对烟曲霉的杀菌活性具有时间和浓度依赖性（例如，4mg/L的泊沙康唑在24小时内杀死>99%的烟曲霉分生孢子）。这些结果表明，总体而言，泊沙康唑对曲霉菌株具有更好的活性和更小的MIC范围，包括那些对两性霉素B、伊曲康唑和伏立康唑敏感性降低的菌株。
