医院感染光滑念珠菌耐药性及流行病学分析

摘要/Abstract

摘要： 目的　分析仁济医院光滑念珠菌的基因分型以及不同基因型光滑念珠菌的药物敏感性结果，以了解仁济医院光滑念珠菌的耐药性和流行情况，并探讨两者间是否存在相关性。方法　运用多位点序列分型（MLST）技术，对34株光滑念珠菌的6个管家基因进行测序分析，利用Clustalx软件与MLST数据库进行序列比对，确定其等位基因谱型及菌株序列型（ST）。利用Clustalx软件绘制进化树，同时通过eBURST程序将菌株分为各个克隆系，以比较不同基因型之间亲缘关系的远近。采用ATB FUNGUS半自动真菌鉴定和药物敏感性分析系统进行药物敏感性试验，结合基因分型结果，运用Ridit分析方法探究两者的联系。结果　34株光滑念珠菌经MLST分型，得到6个ST，其中ST-7 27株，占总数的79.4%（27/34）；ST-10 3株，占总数的8.8%（3/34），其余4型（ST-3、ST-15、ST-43、ST-55）各1株。34株光滑念珠菌对氟胞嘧啶、两性霉素B 100.0%敏感，对伏立康唑和氟康唑的敏感率分别为97.1%和91.2%，伊曲康唑抑菌效果差，敏感率仅11.8%。以ST-7为标准组，氟康唑、伏立康唑及伊曲康唑药物组中ST-10组及其他ST组均包含标准组的平均Ridit值。结论　ST-7为仁济医院光滑念珠菌中优势菌株；光滑念珠菌的耐药谱与基因型相关性差。

关键词: 光滑念珠菌, 多位点序列分型, 药物敏感性分析

Abstract: Objective　To investigate genotypes and drug susceptibility of Candida glabrata isolated from Renji Hospital in order to study its drug-resistance and epidemic situation， and investigate their correlation. Methods　Multilocus sequence typing （MLST）technique was introduced to identify sequences of 6 housekeeping genes from 34 isolates of Candida glabrata. The results were compared with sequence information in MLST databases by Clustalx software to determine a strain allelic profile and sequence type（ST）. By drawing the phylogenetic tree by Clustalx software， the isolates were classified into various clonal complexes by eBURST program to compare the genetic relationship. ATB FUNGUS semi-automatic system was used to test the drug susceptibility. Ridit analysis method was used to analyze the correlation between the genotypes and drug susceptibility. Results　The 34 isolates belonged to 6 clone sequences. ST-7 had the most proportion of 79.4%（27/34）. There were 3 isolates belonged to ST-10，accounting for 8.8%（3/34）， and the remaining 4 isolates belonged to ST-3，ST-15， ST-43 and ST-55，respectively. A total of 34 isolates of Candida glabrata were 100.0% sensitive to fluorocytosine and amphotericin，while the sensitive rates of voriconazole and fluconazole were 97.1% and 91.2%，respectively.The effect of itraconazole was poor with the sensitive rate of 11.8% As ST-7 for the standard group，the Ridit values in the group of ST-10 and other types of ST were included the mean Ridit value of the standard group in fluconazole，voriconazole and itraconazole. Conclusions　ST-7 is the dominant genotype in Renji Hospital. No correlation between the Candida glabrata genotype and its drug susceptibility is found.

郑冰;姚冬婷;应春妹;汪雅萍;张灏旻;杨俊. 医院感染光滑念珠菌耐药性及流行病学分析[J]. 检验医学, 2012, 27(6): 461-466.

ZHENG Bing;YAO Dong-Ting;YING Chun-Mei;WANG Ya-Ping;ZHANG Hao-Min;YANG Jun. Epidemiology and drug-resistance analysis of nosocomial infection of Candida glabrata[J]. , 2012, 27(6): 461-466.

参考文献

［1］Li L，Redding S，Dongari-Bagtzoglou A.Candida glabrata：an emerging oral opportunistic pathogen[J].J Dent Res，2007，86 （3）:204-215.
[2]Dodgson AR， Pujol C， Denning DW， et al.Multilocus sequence typing of Candida glabrata reveals geographically enriched clades[J]. J Clin Microbiol， 2003， 41（12）: 5709-5717.
［3］Pfaller MA，Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem[J]. Clin Microbiol Rev， 2007，20（1）:133-163.
［4］Richardson M， Lass-Flrl C.Changing epidemiology of systemic fungal infections[J].Clin Microbiol Infect，2008 ，14（Suppl 4）:5-24.
［5］Bodey GP，Mardani M，Hanna HA，et al.The epidemi-ology of Candida glabrata and Candida albicans fungemia in immunocompromised patients with cancer[J]. Am J Med，2002，112（5）: 380-385.
［6］Lin CY，Chen YC， Lo HJ，et al. Assessment of Candida glabrata strain relatedness by pulsed-field gel electrophoresis and multilocus sequence typing[J]. J Clin Microbiol，2007 ，45（8）: 2452-2459. 
［7］Lott TJ，Frade JP，Lockhart SR. Multilocus sequence type analysis reveals both clonality and recombination in populations of Candida glabrata bloodstream isolates from U.S. surveillance studies[J]. Eukaryot Cell， 2010，9（4）:619-625.
［8］Wong-Beringera A， Hindler J， Brankovic L， et al. Clinical applicability of antifungal susceptibility testing on non-Candida albicans species in hospitalized patients[J]. Diagn Microbiol Infect Dis， 2001， 39（1）:25-31.
［9］Hazen KC， Baron EJ，Colombo AL， et al.Comparison of susceptibilities of Candida spp. to fluconazole and voriconazole in a 4-year global evaluation using disk diffusion[J].J Clin Microbiol，2003，41（12）:5623-5632.
［10］Pfaller MA， Diekema DJ， Gibbs DL， et al.Results from the ARTEMIS DISK global antifungal surveillance study， 1997 to 2005: an 8.5-year analysis of susceptibilities of Candida species and other yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing[J].J Clin Microbiol， 2007， 45（6）:1735-1745.
［11］张军民，席丽艳，鲁长明，等.医院分离深部真菌菌株流行病学调查和药敏试验研究[J].中华检验医学杂志，2007，30（1）:27-30.
［12］Alexander BD， Byrne TC， Smith KL， et al.Compara-tive evaluation of Etest and sensititre yeastone panels against the Clinical and Laboratory Standards Institute M27-A2 reference broth microdilution method for testing Candida susceptibility to seven antifungal agents[J].J Clin Microbiol， 2007，45（3）:698-706.

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