【作者】 陈集敏；

【导师】 梁伶；

【作者基本信息】 广西医科大学 ， 皮肤性病学， 2010， 硕士

【摘要】 目的为临床选择高效低毒的抗真菌药物治疗马尔尼菲青霉病(Penicilliosis marneffei, PSM)提供理论参考,并据此实验结果分析和探讨马尔尼菲青霉菌(Penicillium marneffei, PM)竹鼠寄生株与临床人分离株的相关性,为PSM的传播途径和致病机制的研究提供理论参考。方法按临床实验室标准委员会(CLSI,原称NCCLS)颁布的M27-A2和M38-A方案采用新型抗真菌药物伏立康唑(voriconazole, VCZ)与常用抗真菌药物伊曲康唑(Itraconazole, ICZ)、氟康唑(Fluconazole, FCZ)、特比奈芬(Terbinafine, TBF)及两性霉素B(Amphotericin B, AMB)同时对PM广西野生竹鼠寄生株14株与临床人分离株25株的菌丝相(25°C)和酵母相(37°C)进行体外抗真菌药敏试验,测定各药分别在两种温度相下对两种不同来源菌株的最小抑菌浓度(MIC值),纵向比较同一温度下PM临床人分离株与寄生株对同一药物的MIC值的差异,横向比较两种不同来源菌株分别在酵母相和菌丝相下对同一种药物的MIC值的差异,分析和探讨新型抗真菌药物VCZ与4种常用抗真菌药物对PM的敏感性差异,并分析PM竹鼠寄生株与临床人分离株的相关性。另外讨论25株PM临床人分离株酵母相的体外抗真菌药敏试验结果与其临床患者的治疗效果的关系,以此分析体外抗真菌药敏试验的临床意义。结果(1)PM临床人分离株与竹鼠寄生株在新型抗真菌药物VCZ的作用下其MIC值在本实验5种药物中最低,常用抗真菌药物ICZ和TBF次之,再次是AMB,而FCZ的MIC值最高;(2)同一温度相下PM临床人分离株与竹鼠寄生株对同一药物的MIC值无明显差异,P>0.05;(3)同一菌株分别在菌丝相和酵母相下对同一种抗真菌药物的MIC值不完全相同;(4)25株PM临床人分离株酵母相的体外抗真菌药敏试验结果与其临床患者的治疗效果存在异同性。结论(1)PM临床人分离株与竹鼠寄生株对新型抗真菌药物VCZ的敏感性最强,常用抗真菌药ICZ、TBF次之,AMB为中度敏感,FCZ的敏感性稍差;(2)同一温度相下PM临床人分离株与竹鼠寄生株对同一抗真菌药物的敏感性一致,提示两种菌株可能存在一定相似性;(3)同一菌株分别在菌丝相和酵母相下对同一种抗真菌药物的敏感性不完全相同,提示菌相的改变有可能影响PM对部分抗真菌药物的敏感性;(4)体外抗真菌药敏试验结果对临床治疗PSM的药物选择仅提供参考性。更多还原

【Abstract】 Objective In order to provide a theoretical reference for the choice of clinical treatment to Penicilliosis marneffei(PSM) with efficient and low toxici- ty antifungal drugs,and then analyz the relevance of Penicillium marneffei(PM) between the isolates from wild-Rhizomys and clinical patients base on the expe- riment results. These provide a theoretical reference for the studies of the trans- mission and pathogenesis of PSM.Method According to the M27-A2 and M38-A programs promulgated by Clinical and Laboratory Standards Institute(CLSI formerly the NCCLS),an antifungal drug susceptibility test in vitro had been conducted for the mycelial forms(25°C) and yeast forms (37°C) of PM between fourteen wild-Rhizomys isolates and twenty-five clinical isolates with the new antifungal drugs voricon- azole(VCZ) and the commonly used antifungal drugs just like Itraconazole (ICZ)、fluconazole (FCZ)、terbinafine (TBF) and amphotericin B (AMB). We measured the minimum inhibitory concentration (MIC) of each drug on both the mycelial and yeast forms of the two different source isolates respectively,and then compared the MICs of one drug for the wild-Rhizomys isolates and clinical isolates in same forms,and compared the MICs of the same drug for the yeast and mycelial forms of the same isolates.Base on the comparison,we analy- zed the difference of the susceptibility of new antifungal drug VCZ and the other four commonly used antifungal drugs, and analyzed the relevance of the wild-Rhizomys isolates and clinical isolates.Furthermore,we discussed the relat- ionnship of the results of antifungal susceptibility test of twenty-five clinical isolates in yeast forms and the treatment of the twenty-five corresponding patie- nts, and base on these we analyzed the clinical significance of the antifungal susceptibility test in vitro.Results:(1) The MICs of new antifungal drug VCZ for the two different source isolates were the lowest one in the five drugs used in the experiment,and the MICs of commonly used antifungal drugs ICZ and TBF were lower than AMB and FCZ, but higher than VCZ, the highest FCZ, Intermediated AMB; (2) There were not exactly different between the MICs of the same drugs for clinic- al isolates and wild-Rhizomys isolates under the same temperature, P>0.05; (3)The MICs of the same drug for the yeast and mycelial forms of the same isolate were not exactly the same; (4)The results of antifungal susceptibility test of twenty-five clinical isolates in yeast forms and the treatment of the twenty-fi ve corresponding patients were not exactly the same.Conclusions :(1) The PM of clinical and wild-Rhizomys isolates both are the most susceptible to VCZ in the experiment,and the two different source iso- lates also show greater susceptibilities to ICZ and TBF than to AMB and FCZ, while AMB moderately sensitive,and FCZ less sensitive; (2) Under the same temperature,the two different source isolates show greater similar susceptibiliti- es to the same antifungal drug, and this indicate the two different source isolates may have some possible relevance; (3) The PM yeast and mycelial forms display not exactly the same susceptibilities to the same antifungal drugs, this indicat the sensitivity of PM to the same antifungal drugs will be affected when their forms changed; (4) The results of antifungal susceptibility test in vitro are only the theoretical reference for the choice of clinical treatment to PSM .更多还原