Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan; Graduate Institute of Medicine, College of Medicine,Kaohsiung Medical University, Kaohsiung City, Taiwan.
Kaohsiung J Med Sci. 2012 Jun;28(6):306-15. doi: 10.1016/j.kjms.2011.11.011. Epub 2012 Apr 4.
The emergence of antifungal resistance in Candida species has raised concern in recent years, especially resistance toward triazole. Several newer triazole antifungal agents have been introduced which have a broader spectrum for fungal infections, such as voriconazole. However, cross-resistance among triazoles is a major concern with regard to their clinical application. Antifungal susceptibility was performed using E-test for 166 clinical isolates (29 blood and 137 nonblood isolates) in 2003 and 2004. We applied pulsed-field gel electrophoresis for genotyping. Ninety isolates of C. albicans, 47 isolates of C. tropicalis, 27 isolates of C. glabrata, and two isolates of C. krusei were included. All isolates were susceptible to amphotericin B. Eleven (40.7%) of the 27 C. glabrata had intermediate resistance to caspofungin. Forty-seven (28.3%) of the 166 isolates were not susceptible to fluconazole, including two C. albicans, 16 C. tropicalis, 27 C. glabrata, and two C. krusei isolates. All except seven of the C. glabrata isolates were susceptible to voriconazole. All the triazole drugs had a positive correlation among their minimum inhibitory concentrations (MICs). Fluconazole MIC was a good predictor for susceptibility to voriconazole, as determined using a receiver operating characteristic curve. Furthermore, a high diversity of pulsotypes for the 27 clinical isolates of C. glabrata was observed. Previous fluconazole exposure within 3 months was associated with reduced triazole susceptibility for C. glabrata. We demonstrated a significant positive correlation of MIC values among the four tested triazole drugs. No amphotericin B and caspofungin resistant isolates were found in this study. The cross-resistance to triazole among C. glabrata isolates was associated with previous fluconazole exposure as opposed to clonal spreading. Selection pressure due to fluconazole use may play a major role in triazole cross-resistance.
近年来，念珠菌属真菌的抗药性问题引起了关注，尤其是对三唑类药物的抗药性。已经引入了几种新型三唑类抗真菌药物，它们对真菌感染具有更广泛的谱，例如伏立康唑。然而，三唑类药物之间的交叉耐药性是其临床应用的主要关注点。2003 年和 2004 年，我们使用 E 试验对 166 株临床分离株（29 株血液分离株和 137 株非血液分离株）进行了抗真菌药敏试验。我们应用脉冲场凝胶电泳进行基因分型。包括 90 株白念珠菌、47 株热带念珠菌、27 株光滑念珠菌和 2 株克柔念珠菌。所有分离株均对两性霉素 B 敏感。27 株光滑念珠菌中有 11 株（40.7%）对卡泊芬净呈中介耐药。166 株分离株中有 47 株（28.3%）对氟康唑不敏感，包括 2 株白念珠菌、16 株热带念珠菌、27 株光滑念珠菌和 2 株克柔念珠菌。除了 7 株光滑念珠菌外，所有分离株均对伏立康唑敏感。所有三唑类药物的最低抑菌浓度（MIC）之间存在正相关。使用受试者工作特征曲线确定，氟康唑 MIC 是预测伏立康唑敏感性的良好指标。此外，我们观察到 27 株光滑念珠菌临床分离株的脉冲场凝胶电泳带型高度多样化。在 3 个月内有氟康唑暴露史的患者，其光滑念珠菌对三唑类药物的敏感性降低。我们发现四种测试的三唑类药物之间的 MIC 值有显著的正相关。在这项研究中，没有发现耐两性霉素 B 和卡泊芬净的分离株。光滑念珠菌对三唑类药物的交叉耐药性与氟康唑暴露有关，而不是与克隆传播有关。由于氟康唑的使用而产生的选择压力可能在三唑类药物的交叉耐药性中起主要作用。
