摘要
目的了解四川地区隐球菌临床分离株基因分型及体外临床常用抗真菌药物敏感性情况。方法采用针对URA5基因PCR产物的限制性片段长度多态性（RFLP）方法对收集自我校华西医院的92株隐球菌临床分离株进行基因分型;采用E-test法检测临床常用抗真菌药物两性霉素B（AMB）、氟胞嘧啶（FC）、氟康唑（FCA）、伊曲康唑（ITR）和伏立康唑（VRC）对隐球菌分离株的最低抑菌浓度（MIC）范围,并计算其MIC50、MIC90。结果92株隐球菌中,91株为新生隐球菌VNⅠ型,1株为格特隐球菌VGⅡ型。5种抗真菌药物对92株隐球菌临床株的MIC值范围、MIC50、MIC90值分别如下：两性霉素B为〈0.002~2μg/mL、0.19μg/mL和0.75μg/mL;氟胞嘧啶为0.5~〉32μg/mL、4μg/mL和8μg/mL;氟康唑为0.5~32μg/mL、3μg/mL和8μg/mL;伊曲康唑为0.064~2μg/mL、0.5μg/mL和1.5μg/mL;伏立康唑为0.004~0.19μg/mL、0.047μg/mL和0.094μg/mL。其中3株（3.3%）对两性霉素B耐药,4株（4.3%）对氟胞嘧啶耐药,25株（27.2%）对伊曲康唑耐药,未发现对氟康唑耐药的菌株,所有菌株对伏立康唑敏感。格特隐球菌（1株）对氟胞嘧啶耐药,对氟康唑剂量依赖敏感。不同时间段隐球菌对5种抗真菌药物的MIC值比较,差异均具有统计学意义。随时间推移,两性霉素B及氟胞嘧啶的MIC值有所升高,唑类药物MIC值变化无规律。结论四川地区隐球菌以新生隐球菌VNⅠ型为主,存在格特隐球菌VGⅡ型。除伊曲康唑外,隐球菌对其他抗真菌药物敏感性高,仅少数菌株对两性霉素B及氟胞嘧啶耐药。
Objective To determine the genotypes and in vitro antifungal susceptibility of Cryptococcus strains isolated from Sichuan Province. Methods Ninety two clinical isolates of Cryptococcus spp. were collected from West China Hospital. Genotyping of the URA.5 gene was accomplished by restriction fragment length polymorphism. The minimum inhibitory concentrations （MIC） of the isolates to 5 antifungals, including amphotericin B, flueytosine, fluconazole, itraconazole and voriconazole were determined by agar-based E-test method. The MIC50 and MICg0 were calculated based on MICs. Results Among the 92 clinical isolates, 91 were molecular type VN I and one was VG Ⅱ. The susceptibility range, MIC50 and MIC90 of the isolates to five antifungals were as follows： （〈0. 002-2） μg/mL, 0. 19 μg/mL and 0. 75 μg/mL for amphotericin B; （0. 5-〉 32） μg/mL, 4 μg/mL and 8 μg/mL for flucytosine; （0. 5-32） μg/mL, 3μg/mL and 8 μg/mL for uconazole; （0.064-2） μg/mL, 0. 5μg/mL and 1. 5 μg/mL for itraconazole; （0. 004-0. 19） μg/mL, 0. 047 μg/mL and 0. 094 μg/mL for voriconazole. Three （3.3%） isolates were resistant to amphotericin B, 4（4.3%） to flucytosine and 25 （27.2%） to itraconazole. No isolate was resistant to flueonazole and all isolates were susceptible to voriconazole. The isolate Cryprococcus gattii was resistant to flucytosine, while S-DD was resistant to fluconazole. There were significant differences in the MICs of the strains isolated from different periods. The MICs of the isolates to amphotericin B and flucytosine increased over time. Conclusion VNI molecular type is the major genotype of Cryprococcus in Sichuan. All the agents have good in vitro activities against the tested strains except itraconazole. A few stains are resistant to amphotericin B and flucytosine.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2015年第1期82-86,共5页
Journal of Sichuan University(Medical Sciences)
