【作者】 孙士营；

【导师】 罗兵；

【作者基本信息】 青岛大学 ， 病原生物学， 2007， 硕士

【摘要】 目的分析真菌性角膜炎的致病菌种分布情况和体外药敏试验结果,为指导临床治疗提供实验依据。方法统计山东省眼科研究所2000～2006年间真菌性角膜炎病例的培养和菌种鉴定结果,同时选择临床常见的茄病镰刀菌、烟曲霉和黄曲霉三种菌株各15株进行体外药物单独和联合药敏试验,试验药物为二性霉素B、伊曲康唑和氟康唑。结果①6年间共对898份临床标本进行真菌的分离培养,阳性结果770份,阳性率为85.7%。共分离鉴定出12个菌属的27种真菌,其中镰刀菌属占71.0%(547/770),曲霉菌属占10.9%(84/770),链格孢菌属占9.61%(74/770)。致病菌为镰刀菌属的515例患者包括10个菌种,主要为茄病镰刀菌185例(33.8%)、尖孢镰刀菌154例(28.2%)与串珠镰刀菌150例(27.4%),其余32例(5.9%)未能明确致病菌种。84例曲霉菌性角膜炎患者的致病菌包括6个菌种,主要为黄曲霉45例(53.6%)与烟曲霉菌33例(39.3%)。②体外药敏试验结果显示真菌对二性霉素B的敏感性最高(91.1%),对伊曲康唑的敏感性为71.1%,对氟康唑的敏感性较低(51.1%)。镰刀菌对二性霉素B的敏感率最高(80%),明显高于对伊曲康唑和氟康唑的敏感率(x~2=13.400,P＜0.01;x~2=16.425,P＜0.01);对伊曲康唑的敏感率和对氟康唑的敏感率相比无显著性差异(x~2=0.370,P＞0.05)。曲霉菌对伊曲康唑100%敏感,与对二性霉素B的敏感率(96.7%)相比差异无统计学意义(x~2=1.170,P＞0.05);但明显高于对氟康唑的敏感率(x~2=4.615,P＜0.05);曲霉菌对氟康唑和二性霉素B的敏感率相比差异也有统计学意义(x~2=6.280,P＜0.05)。③联合药物试验结果显示二性霉素B与氟康唑联合应用时57.8%具有协同作用,与伊曲康唑联合时31.1%具有协同作用,伊曲康唑和氟康唑联合时55.6%具有协同作用。前两组的协同作用差异有统计学意义(x~2=6.48,P＜0.05),第二组与第三组的协同作用差异有统计学意义(x~2=5.745,P＜0.05),第一组与第三组的协同作用差异无统计学意义(x~2=0.452,P＞0.05)。④二性霉素B单独药敏时MIC为1.060±2.699μg/ml,与伊曲康唑联合时MIC则为0.492±1.396μg/ml,差异有统计学意义(t=3.801,P＜0.01);与氟康唑联合时为0.421±0.823μg/ml,差异有统计学意义(t=3.639,P＜0.05)。伊曲康唑单独药敏时MIC为0.781±6.367μg/ml,与二性霉素B联合应用时则为0.387±3.739μg/ml,差异有统计学意义(t=3.514,P＜0.01);与氟康唑联合时为0.523±3.468μg/ml,差异有统计学意义(t=4.136,P＜0.01)。氟康唑单独药敏时MIC为47.760±24.427μg/ml,与伊曲康唑联合应用时则为17.549±19.041μg/ml,差异有统计学意义(t=9.852,P＜0.01);与二性霉素B联合时为16.757±15.600μg/ml,差异有统计学意义(t=10.804,P＜0.01)。结论①镰刀菌、曲霉菌和链隔孢霉是真菌性角膜炎主要的致病菌种。②治疗真菌性角膜炎时首选二性霉素B,曲霉菌感染时也可首选伊曲康唑,但氟康唑作用较差。③联合用药时可选择二性霉素B和氟康唑或伊曲康唑和氟康唑联合,二性霉素B和伊曲康唑联合时效果可能较差。④药物联合使用时参考药敏结果调整剂量。更多还原

【Abstract】 Objective To analyze the pathogens distribution and in vitro drug sensitivity in fungal keratitis during 2000～2006 in Shandong Province.Methods Samples by corneal scrapings and corneal buttons from keratoplasties were subjected to fungal cultures and identifications,and 45 isolates were investigated the in vitro drug sensitivity of AMB、FCZ and ICZ alone and interactively.Results①898 patients were diagnosed as fungal keratitis from 2000 to 2006,of which 770(85.7%) were positive in fungal culture.12 genus and 27 species fungi were identified in 770 cases,of which the common pathogens were 547 Fusarium(71.0%,547/770),84 Aspergillus(10.9%,84/770),and 74 Alternaria(9.6%,74/770) respectively. In the genus Fusarium,10 species were included except for 32 cases with the pathogens unidentified to the species level, and the main species were 185 F.Solani(33.8%),154 F.oxysporum(28.2%) and 150 F.moniliforme(27.4%).6 species were involved in the genus Aspergillus,with A.flavus(53.6%) and A.fumigatus(39.3%) being the common species.②In the drug sensitivity test in vitro,the total susceptibility rate of AMB、ICZ and FCZ was 91.1%、71.1%and 51.1%.AMB was more sensitive than ICZ and FCZ for Fusarium(P＜0.01).As for Aspergi llus,AMB and ICZ were more sensitive than FCZ(P＜0.05).③The combination drug sensitivity test of AMB and FCZ showed that the synergestic was 57.8%,that of AMB and ICZ combination were 31.1%,ICZ and FCZ were 55.6%.The rates of synergestic between the combination AMB & FCZ and combination FCZ&ICZ were higher than that of cmobination AMB & ICZ(P＜0.05).④The geometric mean MICs of the three agents were significantly reduced in the combination drug senitivity test(P＜0.05).Conclusions①Genus Fusarium,Aspergillus and Alternaria are the main pathogens in fungal keratitis in Shandong Province from 2000 to 2006.②AMB was the first chose for keratitis therapy,ICZ could be thought first when the pathogenic was Aspergillus.FCZ was not good selection for keratitis.③The combination of AMB and FCZ and the combination ICZ and FCZ were better than AMB and ICZ combination in keratitis therapy.④The dose of drug should be adjust in clinical therapy refer to the in vitro drug sensitivity test.更多还原