真菌性角膜炎致病菌种的变迁及体外药物敏感试验研究

Pathogens diversity and in vitro drug sensitivity test in fungal keratitis

目的回顾分析2000-2006年山东省真菌性角膜炎致病菌菌种的分布、变迁及部分常见致病菌对抗真菌药物的敏感性。方法对真菌性角膜炎患者的溃疡组织刮片和角膜移植术中取下的病变角膜片标本进行真菌培养及菌种鉴定，分析致病菌的构成及其随年份的变化和山东省眼科研究所开展真菌体外药敏试验以来的试验结果。结果2000-2006年间，共有898例患者诊断为真菌性角膜炎，770例（85．7％）真菌培养阳性。其中首位的致病菌属为镰刀菌属（547例，71．0％），历年百分比分别为75．5％、72．8％、71．5％、75．2％、76％、68．8％和56．4％；曲霉菌属（84例，10．9％）是第2位的致病菌，历年所占百分比为15．1％、15．2％、13．1％、10．2％、10．4％、8．0％和6．9％；链格孢属（74例，9．6％）位居第3位，历年所占百分比分别为1．9％、3．3％、3．7％、6．6％、8．8％、12．0％和29．7％。镰刀菌属主要菌种为茄病镰刀菌（33．8％）、尖孢镰刀菌（28．2％）与串珠镰刀菌（27．4％）；曲霉菌属主要菌种为黄曲霉（53．6％）与烟曲霉菌（39．3％）。常见真菌对两性霉素B、特比萘芬、伊曲康唑、5-氟胞嘧啶和氟康唑MIC值的几何均数分别为0．647、0．714、1．624、15．108和27．070μg／ml。镰刀菌属5种抗真菌药物MIC的几何均数分别为0．899、0．893、3．077、37．124和21．687μg／ml；曲霉菌属分别为0．794、0．591、0．416、23．973和7．127μg／ml；链格孢属分别为0．409、0．479、0．433、11．655和7．104μg／ml。结论镰刀菌属、曲霉菌属和链格孢属是山东省真菌性角膜炎前3位的致病菌属。2000至2006年间，镰刀菌属始终居于真菌性角膜炎致病菌的首位；其次为曲霉菌属，比例呈下降趋势；链格孢属居于第3位，比例呈逐年升高趋势。镰刀菌属对两性霉素B和特比萘芬MIC值的几何均数低，对伊曲康唑、5-氟胞嘧啶和氟康唑MIC值的几何均数高。曲霉菌属和链格孢属对5种抗真菌药物MIC值的几何均数较镰刀菌都低。

Objective To analyze the distribution, diversity, and the sensitivity of common pathogen species to antifungal drugs in fungal keratitis during 2000 - 2006 in Shandong province. Methods Samples from corneal scrapings and corneal buttons from keratoplasties were used for fungal culture and identification. The distribution and diversity of the pathogens in different years were analyzed. The sensitivity of some common species to antifungal drugs were tested. Results A total of 898 patients were diagnosed as fungal keratitis, in which 770 （85.7%） were positive in fungal culture. Pathogens in 748 cases caused by fungal infection were identified, of which 547 cases were caused by Fusarium （71.0%）. The prevelence of Fusarium from 2000 to 2006 was 75.5%, 72. 8%, 71.5%, 75.2%, 76%, 68. 8% and 56.4% respectively. Eighty-four cases were caused by Aspergillus（ 10. 9% ） , which accounted for 15.1% , 15.2% , 13.1% , 10. 2% , 10.4% , 8.0% and 6. 9% of the cases from 2000 to 2006, respectively. Seventy-four cases were caused by Alternaria （ 9. 6% ） , the percentage of which during 2000 - 2006 was 1. 9% , 3.3% , 3.7% , 6. 6% , 8.8% , 12.0 and 29.7% respectively. In genus Fusarium, 10 species were found and the most common species were Fusarium Solani （ 33.8% ） , Fusarium oxysporum （ 28. 2% ） and Fusarium moniliforme（ 27. 4% ）. Six species were identified in genus Aspergillus, with Aspergillus flavus （53.6%） and Aspergillus fumigatus （39. 3% ） being the most common species. The geometric mean MICs of amphotericin B, terbinafin, itraconazole, 5-flucytosine and fluconazole against the common species were 0. 647, 0. 714, 1. 624, 15. 108 and 27. 070 p^g/ml, respectively. The mean MICs of the above five antifungal drugs against Fusarium were 0. 899, 0. 893, 3. 077, 37. 124 and 21. 687 μg/ml, respectively, and for Aspergillus, the mean MICs of these agents were 0. 794, 0. 591, 0. 416, 23. 973 and 7. 127 μg/ml, respectively; for Alter naria, the MICs were 0. 409,0. 479,0. 433,11. 655 and 7. 104μg/ml, respectively. Conclusions Genus Fusarium, Aspergillus and Alternaria were the predominant pathogens in fungal keratitis in Shandong Province. During 2000 - 2006, Fusarium was the most common one, followed by Aspergillus. The percentage of Aspergillus decreased annually. The third most common pathogen, Alternaria increased during the period. The geometric mean MICs of amphotericin B and terbinafin against Fusarium were lower than those of itraconazole, 5-flucytosine and fluconazole. The MICs of these five anti-fungal drugs against Aspergillus and Alternatia were lower than those for Fusarium.