2007至2016年我国北方地区真菌性角膜炎病原学及药物敏感性分析

Analysis of etiology and in vitro drug susceptibility of fungal keratitis in northern China

目的探讨2007至2016年真菌性角膜炎的病原学、药物敏感性特征及变迁。方法回顾性系列病例研究。收集北京同仁眼科中心门诊2007年1月至2016年12月疑为真菌性角膜炎并送检真菌培养的标本5654份。标本接种于马铃薯葡萄糖琼脂斜面培养基，培养3～10d分离阳性标本菌落。丝状真菌依据形态学进行种属鉴定，酵母样真菌采用API20CAux鉴定菌种。药物敏感性试验采用Rosco纸片扩散法，药物包括那他霉素、特比萘芬、伊曲康唑、氟康唑、两性霉素B、伏立康唑。计数资料的组间差异应用卡方检验，阳性率及构成比的比较采用Spearman相关分析。结果真菌培养阳性率为26．1％（1475／5654）。标本真菌培养阳性的患者中，男女比例为1．77：1，年龄为（49．0±16．9）岁。成年患者（〉20岁且≤60岁）最多、阳性率最高，占总阳性标本数的77．7％（1146／1475）。培养阳性的真菌中，镰刀菌属最多，占53．5％（789／1475），其次为曲霉属17．5％（259／1475）、链隔孢属13．8％（203／1475）。那他霉素敏感率最高，为92．3％（410／1475），其次为特比萘芬78．5％（1093／1475）、伏立康唑41．0％（338／1475）、两性霉素B40．7％（553／1475）。结论成年、男性患者为真菌性角膜炎的主要患者群。镰刀菌属、曲霉属、链隔孢属为北方地区3大常见种属，且存在季节性菌谱变化。那他霉素应为经验性治疗的首选药物，对曲霉属感染首选特比萘芬。氟康唑耐药率高，不宜单独使用。

Objective To analyze the etiology, drug susceptibility and etiological changes of fungal keratitis so as to to provide reference for clinical diagnosis and treatment. Methods Retrospective case series study. A total of 5 654 copies of specimens for fungal culture were collected from Outpatients suspected of fungal keratitis in Beijing Tongren Ophthalmic Center during January 2007 and December 2016. Specimens were inoculated on Potato dextrose agar （PDA） slant medium, incubated at 30℃ and 40% humidity constantly for 3 to l0 days. Filamentous fungi isolated from positive cultures were identified according to morphological traits. Yeast-like fungi were identified by API 20 C Aux. Drug susceptibility tests were performed by using ROSCO disk diffusion method, which included natamycin, terbinafine, itraconazole, fluconazole, amphotericin B, voriconazole. The Chi-square test and Spearulan correlation analysis were performed using SPSS 20.0 software. Results The positive rate of culture was 26.1%. In positive patients, the ratio of male to female was 1.77： 1, and the age range was I 1 days to 95 years. The mean age was 49.0±16.9 years. Among isolated fungi, Fusarium sp. was the most common genus, aceounting for 53.5% （789 strains）, followed by 17.5% of Aspergillus sp. （259 stains） and 13.8% of Alternaria sp. （203 stains）. The sensitive rate of natamycin was 92.3% （410 strains）, followed by that of terbinafine as 78.5% （1 093 strains）, voficonazole as 41.0% （338 strains）, amphoteriein B as 40.7% （553 strains）. Conclusion The predominant patients of fungal keratitis are adult and male. Fusarium sp., Aspergillus sp., and Alternaria sp. are three common species in northern china with seasonal changes in their proportion.Natamycin should be the preferred drug for empirical treatment. The preferred empirical treatment for Aspergillus sp. is terbinafine. Fluconazole should not be used alone due to the high resistant rate.